Publications by authors named "Mohsen Tehrani"

37 Publications

Expression Analysis of Fyn and Bat3 Signal Transduction Molecules in Patients with Chronic Lymphocytic Leukemia.

Asian Pac J Cancer Prev 2020 Sep 1;21(9):2615-2621. Epub 2020 Sep 1.

Gastrointestinal Cancer Research Center, Non-Communicable Diseases Institute, Mazandaran University of Medical Sciences, Sari, Iran.

Background: Chronic lymphocytic leukemia (CLL) is correlated with defects in T-cell function resulting imparity in antitumor immune responses. Tim-3 is a co-inhibitory immune checkpoint receptor expressed on exhausted T-cells during tumor progression. Fyn and Bat3 are two important adaptor molecules involved in inhibition and activation of Tim-3 downstream signaling, respectively. In this study, the expression of Tim-3, Fyn, and Bat3 mRNA was evaluated in CLL patients.

Methods: Peripheral blood mononuclear cells (PBMCs) were isolated from 54 patients with CLL and 34 healthy controls. Total RNA was extracted from all samples and applied for cDNA synthesis. The relative expression of Tim-3, Fyn, and Bat3 mRNA was determined by TaqMan Real-Time PCR using GAPDH as an internal control.

Results: Tim-3 mRNA expression was not significantly different between CLL patients and healthy controls. Fyn mRNA expression was significantly lower in CLL patients and conversely, Bat3 mRNA expression was higher in CLL patients compared to healthy controls. Interestingly, the mRNA expression of Fyn inhibitory adaptor molecule was remarkably associated with expression of Tim-3 in CLL patients.

Conclusion: We have highlighted for the first time the expression of Fyn and Bat3 adaptor molecules in CLL patients. Our data demonstrated the strong correlation between the expression of Tim-3 and Fyn inhibitory molecules in CLL implying an important role for Tim-3-Fyn cooperation in induction of T-cell exhaustion.
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http://dx.doi.org/10.31557/APJCP.2020.21.9.2615DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7779459PMC
September 2020

Blockade of PD-1 and TIM-3 immune checkpoints fails to restore the function of exhausted CD8 T cells in early clinical stages of chronic lymphocytic leukemia.

Immunol Res 2020 10;68(5):269-279

Department of Immunology, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.

Blocking antibodies targeting immune checkpoint molecules achieved invaluable success in tumor therapy and amazing clinical responses in a variety of cancers. Although common treatment protocols have improved overall survival in patients with chronic lymphocytic leukemia (CLL), they continue to relapse and progress. In the present in vitro study, the application of anti-PD-1 and anti-TIM-3 blocking antibodies was studied to restore the function of exhausted CD8 T cells in CLL. CD8 T cells were isolated from peripheral blood of 20 patients with CLL, treated with blocking antibodies, and cocultured with mitomycin-frozen non-CD8 T cell fraction as target cells. Cultures were stimulated with anti-CD3/CD28 antibodies to assess the proliferation of CD8 T cells by MTT and stimulated with PMA/ionomycin to measure the levels of CD107a expression and cytokine production by flow cytometry and ELISA, respectively. Our results showed that the blockade of PD-1 and TIM-3 does not improve the proliferation of CD8 T cells in CLL patients. No significant difference was found between control and blocked groups in terms of degranulation properties and production of IFN-γ, TNF-α, IL-2, and IL-10 by CD8 T cells. We observed that pre-treatment of CD8 T cells with blocking antibodies in CLL patients at early clinical stages had no effects on restoring their functional properties. Further in vitro and in vivo complementary studies are required to more explore the utility of checkpoint inhibitors for CLL patients.
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http://dx.doi.org/10.1007/s12026-020-09146-4DOI Listing
October 2020

Paraoxon-induced damage in rat hippocampus is associated with alterations in the expression of apoptosis-related proteins.

Pestic Biochem Physiol 2020 Jun 8;166:104580. Epub 2020 Apr 8.

Department of Physiology, Molecular and Cell Biology Research Center, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran. Electronic address:

To determine the possible role of apoptosis in the development of paraoxon-induced brain damage, we evaluated expression of apoptosis-related proteins, the extent of neuronal damage, and activation of astrocytes in rat hippocampus. Adult male Wistar rats were intraperitoneally injected with one of three doses of paraoxon (0.3, 0.7, or 1 mg/kg) or corn oil (vehicle). After 14 or 28 days, expression of apoptosis-related proteins, including B-cell leukemia/lymphoma-2 (Bcl-2), Bcl-2 associated X protein (Bax), and caspase-3, as well as the number of neurons and glial fibrillary acidic protein (GFAP) positive cells in hippocampus were examined by western blot, cresyl blue staining, and immunohistochemistry, respectively. After 14 and 28 days, Bax and caspase-3 proteins were significantly increased in rats receiving 0.7 and 1 mg/kg of paraoxon. A significant decrease in Bcl-2 protein levels was also observed in 0.7 and 1 mg/kg groups after 14 days and in 1 mg/kg group after 28 days. Animals treated with 1 mg/kg of paraoxon showed a significant decrease in the number of neurons in the CA1 area. Also, those treated with 0.7 and 1 mg/kg of paraoxon showed an increase in the number of GFAP positive cells in both CA1 and CA3 areas as well as a significant decrease in survived neurons in the CA3 area. Our results indicated that neuronal damage induced by convulsive doses of paraoxon in rat hippocampus is mediated in part through apoptosis mechanism. Activation of astrocytes might lead to reduced extent of damage and damage and consequently increased neuronal survival.
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http://dx.doi.org/10.1016/j.pestbp.2020.104580DOI Listing
June 2020

Effects of Paraoxon Exposure on Expression of Apoptosis-Related Genes, Neuronal Survival, and Astrocyte Activation in Rat Prefrontal Cortex.

Neurotox Res 2020 Feb 7;37(2):356-365. Epub 2019 Sep 7.

Department of Physiology, Molecular and Cell Biology Research Center, School of Medicine, Mazandaran University of Medical Sciences, KM 17 Khazarabad Road, Khazar Sq, Sari, Iran.

Paraoxon is the bioactive metabolite of organophosphate (OP) pesticide, parathion. This study aimed to evaluate the expression of apoptosis-related genes and histopathological changes in rat prefrontal cortex following exposure to three different doses of paraoxon. Paraoxon (0.3, 0.7, or 1 mg/kg) or corn oil (vehicle) were intraperitoneally injected to adult male Wistar rats. After 14 or 28 days, mRNA and protein levels of Bax, Bcl-2, and caspase-3 were measured in prefrontal cortex using quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) and western blotting, respectively. In addition, neuronal injury and astrocyte activation were assessed using cresyl violet staining and glial fibrillary acidic protein (GFAP) immune-positive cells, respectively. Treatment with 0.7 and 1 mg/kg of paraoxon increased mRNA and protein levels of Bax and caspase-3 at 14 and 28 days post-exposure, while mRNA and protein levels of Bcl-2 decreased only in 1 mg/kg group after 14 days. Furthermore, a significant decrease in the number of neurons and a significant increase in the number of GFAP-positive cells were observed in rats receiving 0.7 and 1 mg/kg of paraoxon at both time points. Collectively, our results showed that apoptosis is a major mechanism for neuronal damage after exposure to paraoxon. Also, paraoxon-induced neuronal loss was correlated with activation of astrocytes. Since paraoxon-induced neuronal damage is closely related to convulsion, clinical management of convulsion could protect neuronal brain damage.
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http://dx.doi.org/10.1007/s12640-019-00106-xDOI Listing
February 2020

Over-Expression of Immunosuppressive Molecules, PD-L1 and PD-L2, in Ulcerative Colitis Patients.

Iran J Immunol 2019 Mar;16(1):62-70

Department of Immunology, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.

Background: Ulcerative colitis (UC) and Crohn's disease (CD) are the two forms of inflammatory bowel disease (IBD). Adaptive immune responses involving helper T cells play an important role in developing IBDs. Programmed death (PD)-1 and its ligands namely PD-L1 and PD-L2 are negative costimulatory molecules that control T cell motility and formation of an immune synapse between T cells and antigen-presenting cells (APCs).

Objective: To investigate the role of PD-L1 and PD-L2 in patients with UC to clarify the mechanism of IBD development.

Methods: Biopsy specimens were obtained from 50 UC patients and 45 sex- and age-matched control subjects. Total RNA was extracted from all samples and applied for cDNA synthesis. Relative expression of PD-L1 and PD-L2 mRNA was determined using Taqman qRT-PCR.

Results: Relative gene expression levels of both PD-L1 and PD-L2 were higher in UC patients than the control groups (p<0.05 and p<0.01, respectively). Furthermore, both PD-L1 and PD-L2 expressions were positively correlated in all study subjects (r=0.339, p<0.001). However, among the groups with disease severity, the relative gene expression levels of PD-L1 and PD-L2 showed no significant difference.

Conclusions: During IBD, the occurrence of PD-L1 and PD-L2 up-regulation may modulate the chronic inflammation of colonic mucosa.
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http://dx.doi.org/10.22034/IJI.2019.39407DOI Listing
March 2019

Anti-inflammatory effects of the Portulaca oleracea hydroalcholic extract on human peripheral blood mononuclear cells.

Med J Islam Repub Iran 2018 3;32:80. Epub 2018 Sep 3.

Department of Immunology, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.

, known as Purslane, is an annual growing herb with wide distribution around the world and traditionally used to manage several diseases. Different therapeutic properties as an anti-fever agent as well as anti-inflammatory and analgesic effects have been attributed to . The aim of this study was to investigate the effects of aerial extract on production of pro- and anti-inflammatory cytokines by human peripheral blood mononuclear cells (PBMCs). Aerial parts of (stems and leaves) were collected and extracted by percolation using methanol. The optimal and non-cytotoxic dose of hydro-alcoholic extract for cell culture analysis was determined by MTT assay. To assess the antiinflammatory effects of , PBMCs obtained from 12 normal volunteers were cultured in RPMI complete medium and cotreated with E. coli lipopolysaccharide (LPS) and hydro-alcoholic extract. Following 18-hour incubation, culture supernatants were harvested for measurement of secreted TNF-α, IL-6 and IL-10 by ELISA. Statistical analyses were performed using the SPSS v.20, and data analyzed by Kolmogorov-Smirnov, Mann-Whitney U, Kruskal-Wallis and post Hoc tests. P-values<0.05 were considered significant. The optimal non-cytotoxic concentration of aerial extract was defined as 100 μg/ml based on MTT viability assay. hydro-alcoholic extract significantly decreased the concentration of both pro-inflammatory cytokines TNF-α and IL-6 in LPS-stimulated PBMCs (p<0.001 and p<0.001, respectively). However, the concentration of IL-10 as an anti-inflammatory cytokine, did not show any statistically significant change (p=0.390). Our findings highlighted the potential anti-inflammatory properties of in herbal medicine. Future analysis on different constituents of total extract may confirm its therapeutic effects as a promising anti-inflammatory compound.
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http://dx.doi.org/10.14196/mjiri.32.80DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6325294PMC
September 2018

Anxiolytic activity of paraoxon is associated with alterations in rat brain glutamatergic system.

Neurotoxicol Teratol 2019 Jan - Feb;71:32-40. Epub 2018 Dec 19.

Department of Physiology & Pharmacology, Molecular and Cell Biology Research Center, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran. Electronic address:

Exposure to organophosphate (OP) compounds leads to behavioral alterations. To determine whether paraoxon has effects on anxiety, anxiety-like behaviors were assessed in paraoxon-exposed rats. Protein expression of glutamate transporters has also been measured in hippocampus and prefrontal cortex. Three doses of paraoxon (0.3, 0.7, or 1 mg/kg) or corn oil (vehicle) were intraperitoneally injected to adult male rats. At 14 or 28 days after exposure, behavioral tests were done using elevated plus-maze (EPM) or open field tests. Thereafter, animals were sacrificed and both hippocampi and prefrontal cortices were extracted for cholinesterase assay and western blotting. Animals treated with convulsive doses of paraoxon (0.7 and 1 mg/kg) showed an increase in percentage of time spent in open arms and percentage of open arm entries in the EPM. In the open field test, an increase in the time spent in central area was observed in rats treated with the same doses of paraoxon. These effects of paraoxon were independent of any changes in locomotor activity. There was an increase in both astrocytic glutamate transporter proteins (GLAST and GLT-1) in the hippocampus of animals treated with 0.7 and 1 mg/kg of paraoxon. In the prefrontal cortex, protein levels of the GLAST and GLT-1 increased in 0.7 and decreased in 1 mg/kg groups. Only a significant decrease in EAAC1 protein was observed in the prefrontal cortex at 14 days following exposure to 1 mg/kg of paraoxon. Collectively, this study showed that exposure to convulsive doses of paraoxon induced anxiolytic-like behaviors in both behavioral tests. This effect may be attributed to alterations of glutamate transporter proteins in the rat hippocampus and prefrontal cortex.
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http://dx.doi.org/10.1016/j.ntt.2018.12.001DOI Listing
May 2020

Association of P53 gene polymorphism with gastric cancer in Northern Iran as a high-risk region.

Biomed Rep 2018 May 22;8(5):433-438. Epub 2018 Feb 22.

Gastrointestinal Cancer Research Center, Mazandaran University of Medical Sciences, Sari, Mazandaran 48166-33131, Iran.

Gastric cancer has the fourth highest morbidity rate of all cancers worldwide. Genetic factors including alterations in oncogenes and tumor suppressor genes serve an important role in gastric cancer development and progression. The gene acts as a tumor suppressor gene by regulating the cell cycle, DNA transcription and repair, apoptosis, senescence and genome stability. In addition to somatic mutations in cancer development, germline polymorphisms are also involved in different malignancies. The polymorphism of at codon 72 (Arg72Pro) is established as a common variant that increases susceptibility to various cancers. The present case-control study was conducted to evaluate the possible association between this polymorphism and gastric cancer in the Iranian population. A total of 59 patients with gastric cancer and 59 healthy controls were enrolled in the present study. Genomic DNA was extracted from peripheral blood mononuclear cells and genotype analysis was performed using a polymerase chain reaction-based restriction fragment length polymorphism assay. Genotype frequencies did not differ significantly between the patients and controls (P=0.4); the frequencies of the three genotypes Arg/Arg, Arg/Pro and Pro/Pro in gastric cancer patients were 28.8, 49.2 and 22.0%, and in controls were 37.3, 49.2 and 13.6%. Additionally, there were no differences in genotype frequencies based on tumor location, histological differentiation or tumor stage. Based on these findings, it may be concluded that the codon 72 polymorphism does not contribute to gastric cancer susceptibility in Northern Iran.
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http://dx.doi.org/10.3892/br.2018.1070DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5876468PMC
May 2018

CD4+ T Cells are Exhausted and Show Functional Defects in Chronic Lymphocytic Leukemia.

Iran J Immunol 2017 Dec;14(4):257-269

Department of Immunology, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.

Background: Chronic lymphocytic leukemia (CLL) is the most common adult leukemia in the western world. This health problem is caused due to the accumulation of mature B-lymphocytes in the peripheral blood and bone marrow. In the course of cancer, CD4+ T cells become "exhausted" and characterized with poor effector functions and the expression of multiple inhibitory receptors.

Objective: To investigate the frequency and functional properties of exhausted CD4+ T lymphocytes in patients with CLL.

Methods: Peripheral blood mononuclear cells were obtained from 25 untreated CLL patients and 15 healthy volunteers. CLL patients were clinically classified according to the Rai staging system. The frequency of CD4+/Tim-3+/PD-1+ cells was obtained by flow cytometry. To evaluate cell proliferation and cytokine production, CD4+ T cells were isolated and stimulated with phytohemagglutinin and PMA/ionomycin. Concentrations of IL-2, IFN-γ, TNF-α, and IL-10 were measured in the culture supernatants of stimulated cells by the ELISA technique.

Results: The percentage of CD4+/Tim-3+/PD-1+ cells was significantly higher in CLL patients than that of healthy controls. CD4+ T cells from CLL patients showed lower proliferative responses, a lower production of IL-2, IFN-γ, and TNF-α, and a higher production of IL-10, compared to healthy controls. CD4+ T cells from CLL patients in advanced clinical stages showed more exhaustion features than those of early stages.

Conclusion: Given that the exhaustion phase of T cells can be reversible, targeted blocking of immune inhibitory molecules could be a promising tool to restore the host immune responses against leukemic cells in CLL.
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http://dx.doi.org/IJIv14i4A1DOI Listing
December 2017

Upregulation of Galectin-9 and PD-L1 Immune Checkpoints Molecules in Patients with Chronic Lymphocytic Leukemia

Asian Pac J Cancer Prev 2017 08 27;18(8):2269-2274. Epub 2017 Aug 27.

Department of Immunology, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.

Background: Deviation of host immune response by engagement of inhibitory receptors is one of the well-known mechanisms of tumor cells for immune evasion and survival. PD-1/PD-L1 and Tim-3/Gal-9 axes are two major pathways in this area which their contribution has been documented in a variety of malignancies. In this study, Gal-9 and PD-L1 expression was investigated in leukemic cells from patients with Chronic Lymphocytic Leukemia (CLL). Methods: Peripheral blood mononuclear cells (PBMCs) were obtained from 25 untreated CLL patients and 15 sex- and age-matched healthy controls. CLL patients were classified into different clinical stages based on the Rai staging system. Total RNA was extracted from all samples and applied for cDNA synthesis. Relative expression of Gal-9 and PD-L1 mRNA was determined by Real-Time PCR using β-actin as a housekeeping gene. Results: Gal-9 and PD-L1 mRNA was significantly more expressed in CLL patients compared to healthy controls (p<0.0001 and p=0.005, respectively). CLL patients in advanced clinical stages showed higher expression of Gal-9 and PD-L1 in comparison to patients in early clinical stages (p<0.0001 and p=0.004, respectively). Conclusion: Our promising results regarding over-expression of Gal-9 and PD-L1 in CLL patients call future complementary studies to more evaluate and confirm these pathways for immunotherapy approaches of this malignancy. Upregulation of both Gal-9 and PD-L1 in CLL patients with advanced clinical stages introduces them as useful prognostic biomarkers for disease progression.
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http://dx.doi.org/10.22034/APJCP.2017.18.8.2269DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5697491PMC
August 2017

Differential expression of glutamate transporters in cerebral cortex of paraoxon-treated rats.

Neurotoxicol Teratol 2017 Jul 8;62:20-26. Epub 2017 Jun 8.

Department of Physiology & Pharmacology, Molecular and Cell Biology Research Center, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran. Electronic address:

Glutamatergic system is involved in pathological effects of organophosphorus (OP) compounds. We aimed to determine in vivo effects of paraoxon, the bioactive metabolite of parathion, on the expression of glutamate transporters as well as Bax and Bcl2 in rat cerebral cortex. Male Wistar rats received an intraperitoneal (i.p.) injection of one of three doses of paraoxon (0.3, 0.7, or 1mg/kg) or corn oil as vehicle (1ml/kg). After 4 or 18h, cerebral cortices were dissected out and used for quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) and western blot assays to measure mRNA and protein levels, respectively. The cortical glial glutamate transporters (GLAST and GLT-1) were up-regulated in animals treated with 0.7mg/kg of paraoxon, but down-regulated in 1mg/kg group. Neuronal glutamate transporter (EAAC1) was unchanged in 0.7mg/kg treated rats, while reduced in 1mg/kg group. No significant difference was found in the mRNA and protein expression of EAAC1 in animals intoxicated with 0.3mg/kg of paraoxon. Paraoxon (1mg/kg) resulted in an up-regulation of Bax and down-regulation of Bcl2 mRNA levels in the rat cerebral cortex. These results indicate that paraoxon can differentially regulate expression of glutamate transporters at mRNA and protein levels in the cerebral cortex. Changes in the expression of glutamate transporters are closely related to paraoxon-induced seizure activity.
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http://dx.doi.org/10.1016/j.ntt.2017.06.001DOI Listing
July 2017

Tim-3 Up-regulation in Patients with Gastric Cancer and Peptic Ulcer Disease

Asian Pac J Cancer Prev 2017 03 1;18(3):765-770. Epub 2017 Mar 1.

Department of Immunology, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.

Background: T-cell immunoglobulin and mucin domain protein-3 (Tim-3), an inhibitory immunoregulatory receptor, has been recently implicated in tumor biology and tumor-associated immune suppression. In the present study, expression of Tim-3 was evaluated in gastric cancer (GC) and peptic ulcer disease (PUD) at both mRNA and protein levels. Methods: A total of 133 gastric tissue biopsies, comprising 43 from GC cases, 48 from PUD and 42 from non-ulcer dyspepsia (NUD) serving as controls were collected. Additionally, non-neoplastic adjacent tissue biopsies were also obtained from 6 patients with GC. Infection with Helicobacter pylori was determined by the rapid urease test for all participants and H&E staining was conducted for GC and PUD patients. Tim-3 relative mRNA expression was determined by SYBR Green based Real-Time PCR using β-actin as a reference gene. Tim-3 protein expression was also studied by immunohistochemistry in 7 GC, 7 PUD and 10 NUD tissue samples. Results: Tim-3 was expressed at higher levels in GC (p=0.030) and PUD (p=0.022) cases compared to he NUD group. Among paired samples obtained from gastric cancer patients, tumor tissues showed elevated Tim-3 expression (p=0.019) in comparison with adjacent non-neoplastic biopsies. Tim-3 mRNA findings were supported by detection of more Tim-3 protein in cancerous (p=0.002) and ulcerative (p=0.01) tissues than in controls. Tim-3 was similarly expressed in H. pylori positive and negative cases.Conclusion: Higher Tim-3 expression in patients with gastric cancer and peptic ulcer implies that it might be involved in immune regulation and establishment of these gastrointestinal diseases. Targeted immunotherapy by blocking of inhibitory receptors like Tim-3 could be a promising approach for gastric cancer treatment.
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http://dx.doi.org/10.22034/APJCP.2017.18.3.765DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5464497PMC
March 2017

Frequency and functional characterization of exhausted CD8 T cells in chronic lymphocytic leukemia.

Eur J Haematol 2017 Jun 17;98(6):622-631. Epub 2017 Apr 17.

Department of Immunology, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.

Objectives: The phenotypic and functional properties of Tim-3 /PD-1 /CD8 cells as exhausted T cells were investigated in chronic lymphocytic leukemia (CLL).

Methods: Frequency of CD8 /Tim-3 /PD-1 exhausted cells was determined by flow cytometry. For functional analysis, magnetic beads-isolated CD8 T cells were stimulated with PHA and PMA/ionocymin to assess their proliferative responses and cytokine production by MTT and ELISA, respectively. Cytotoxic activity of isolated CD8 T cells was determined using CD107a degranulation assay.

Results: The proportion of exhausted CD8 T cells was significantly higher in CLL compared to controls. Isolated CD8 T cells from CLL showed functional defects in proliferation, degranulation, and cytokines production. While IL-2, TNF-α, and IFN-γ were significantly lower in CLL patients, IL-10 was higher in the patients group. Patients with progressive clinical stages showed higher frequency and dysfunction of exhausted CD8 T cells.

Conclusion: Targeting immune inhibitory receptors to restore the function of tumor surrounding T cells could be helpful for immunotherapy of CLL.
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http://dx.doi.org/10.1111/ejh.12880DOI Listing
June 2017

Enhancing immune responses to a DNA vaccine encoding Toxoplasma gondii GRA14 by calcium phosphate nanoparticles as an adjuvant.

Immunol Lett 2017 05 9;185:40-47. Epub 2017 Mar 9.

Toxoplasmosis Research Center, Mazandaran University of Medical Sciences, Sari, Iran. Electronic address:

Several approaches have been used to improve the immunogenicity of DNA vaccines. In the current study, we constructed the plasmid encoding T. gondii dense granule 14 (GRA14) and investigated the immunological properties of calcium phosphate nanoparticles (CaPNs) as nano-adjuvant to enhance the protective efficacy of pcGRA14. BALB/c mice intramuscularly injected three times at two-week intervals and the immune responses were evaluated using lymphocyte proliferation assay, cytokine and antibody measurements, survival times, and parasite load of mice challenged with the virulent T. gondii RH strain. The results showed that the immune responses were induced in mice receiving pcGRA14 DNA vaccine. Interestingly, pcGRA14 coated with nanoparticles led to statistically significant enhancements of cellular and humoral immune responses against Toxoplasma infection (P<0.05). After challenge with RH strain of T. gondii, immunized mice with pcGRA14 showed prolong survival time compared to control groups (P<0.05). In addition, pcGRA14 coated with nano-adjuvant exhibited the lowest parasitic load in the infected mice tissues. For the first time, our data indicate that the pcGRA14 coated with CaPN was more effective for stimulation of immune responses and should be considered as an adjuvant in the design of vaccines against toxoplasmosis.
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http://dx.doi.org/10.1016/j.imlet.2017.03.006DOI Listing
May 2017

A Study on the Association of Interleukin-1 Cluster with Genetic Risk in Bipolar I Disorder in Iranian Patients: A Case-control Study.

Iran J Allergy Asthma Immunol 2016 Dec;15(6):466-475

Department of Immunology, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.

The pathogenesis of Bipolar I Disorder (BP-I) involves immune-mediated mechanisms, especially an imbalance in pro-inflammatory/anti-inflammatory cytokines in plasma or cerebrospinal fluid. Interleukin-1 (IL-1) gene cluster, coding some of these pro-inflammatory cytokines, might play a role in various neuropathologies related to neuron inflammation. The aim of the present study was to investigate the possible role of IL-1 gene cluster polymorphisms in determining the susceptibility to BP-I in Iranian population. 48 patients with BP-I in Mashhad (in north-eastern Iran), diagnosed by two psychiatrists using SCID (structured clinical interview for DSM disorders) were selected through convenient sampling and were compared with 47 healthy controls, voluntarily enrolled in the study. Patients with non-Persian ethnicity, history of immunoallergic disorders, endocrinopathies, neurologic disorders, and substance-induced mood disorders were excluded from both case and control groups. Genotyping of IL-1 gene cluster polymorphisms, including IL-1a-889, IL-1b +3954, IL-1b-511, and IL-1RN (VNTR) were carried out using Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and compared by SPSS using Fisher's exact and chi-square tests. The frequency of IL-1b-511 CC genotype and C/T allelic frequency were significantly different between BMD patients and healthy controls (p=0.04 and p=0.02, respectively). Among patients, -511 T allele was significantly more frequent in those with a positive history of major depression. Moreover, +3954 T allele was significantly more frequent in early onset BMD patients. The results suggest a positive association between IL-1 gene cluster variation and BP-I. This polymorphism may contribute to genetic vulnerability through its possible role in neuron inflammation.
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December 2016

Association of Nucleotide-binding Oligomerization Domain Receptors with Peptic Ulcer and Gastric Cancer.

Iran J Allergy Asthma Immunol 2016 Oct;15(5):355-362

Department of Immunology, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran AND Molecular and Cell Biology Research Center, Mazandaran University of Medical Sciences, Sari, Iran.

Host innate immunity can affect the clinical outcomes of Helicobacter pylori infection, including gastritis, gastric ulcer, gastric adenocarcinoma, and MALT lymphoma. Nucleotide binding oligomerization domain (NOD)-1 and -2 are two molecules of innate immunity which are involved in the host defense against H. pylori. This study aimed to evaluate the effect of the expression level of NOD1 and NOD2 on the susceptibility to gastric cancer as well as peptic ulcer in individuals with H. pylori infection. The gene expression levels of these molecules were compared in three groups of non-ulcer dyspepsia (NUD) as a control group (n=52); peptic ulcer disease (PUD), (n=53); and gastric cancer (GC), (n=39). Relative expression levels of NOD1 in patients with GC were higher than those of NUD and PUD (p<0.001 and P<0.001, respectively). Similarly in case of NOD1, PUD group showed higher level of expression than NUD group (p<0.01). However, there was no significant difference between H. pylori -positive and -negative patients in NUD, PUD, or GC groups. Moreover, the expression levels of NOD2 showed no significant difference among NUD, PUD, or GC groups, while among H. pylori-positive patients, it was higher in GC group than NUD  and PUD groups (p<0.05 and p<0.01, respectively). In addition, positive correlation coefficients were attained between NOD1 and NOD2 expressions in patients with NUD (R2 Linear=0.349, p<0.001), PUD (R2 Linear=0.695, p<0.001), and GC (R2 Linear=0.385, p<0.001). Collectively, the results suggest that the chronic activation of NOD1 and NOD2 receptors might play a role in the development of gastric cancer.
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October 2016

Alterations in mRNA and protein expression of glutamate transporters in rat hippocampus after paraoxon exposure.

Neurotoxicology 2016 12 18;57:251-257. Epub 2016 Oct 18.

Department of Immunology, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran; Molecular and Cell Biology Research Center, Mazandaran University of Medical Sciences, Sari, Iran. Electronic address:

Organophosphates affect brain function through a variety of mechanisms beyond their shared role as cholinesterase inhibitors. The aim of the current study was to investigate the changes in the expression of glial (GLAST and GLT-1) and neuronal (EAAC1) glutamate transporters at mRNA and protein levels in paraoxon-treated rat hippocampus. Adult male Wistar rats were intraperitoneally treated with either vehicle (corn oil) or one of three dosages of paraoxon (0.3, 0.7 or 1mg/kg). After 4 or 18h, both hippocampi of each rat were collected to detect mRNA and protein expression of glutamate transporters using the quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) and western blotting, respectively. Animals treated with 0.3mg/kg paraoxon showed no difference in mRNA and protein levels of the glutamate transporters when compared with control group. At 4h after exposure with 0.7 and 1mg/kg paraoxon, the expression of GLAST and GLT-1 increased at mRNA and protein levels and remained elevated after 18h. No difference in the expression of EAAC1 at mRNA and protein levels was observed in any paraoxon-treated groups compared with the control group. This study showed an increased expression of glial (GLAST and GLT-1), but not neuronal (EAAC1) glutamate transporters, in adult rat hippocampus following administration of convulsive dosages of paraoxon. These suggest a protective and compensatory adaptation for effective uptake of glutamate in hippocampus induced by paraoxon and thus attenuating seizure activity.
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http://dx.doi.org/10.1016/j.neuro.2016.10.009DOI Listing
December 2016

Regulatory T Cells and Myeloid-Derived Suppressor Cells in Patients with Peptic Ulcer and Gastric Cancer.

Iran J Immunol 2016 Sep;13(3):167-77

Department of Immunology, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.

Background: Regulatory T Cells (Tregs) and Myeloid-Derived Suppressor Cells (MDSCs) are two main regulatory cells modulating the immune responses in inflammation and cancer.

Objective: To investigate and compare Tregs and MDSCs in peptic ulcer and gastric cancer.

Methods: Patients with dyspepsia were selected and divided into three groups of non-ulcer dyspepsia (NUD, n=22), peptic ulcer disease (PUD, n=25), and gastric cancer (GC, n=27) according to their endoscopic and histopathological examinations. Helicobacter pylori infection was diagnosed by rapid urease test and histopathology. The number of peripheral blood CD4+CD25+FoxP3+Tregs and CD14+HLA-DR- MDSCs were determined in all patients, by flow cytometry. The number of FoxP3+ regulatory T cells was also determined by immunohistochemistry (IHC).

Results: The percentage of peripheral blood Treg cells in both PUD (0.81 ± 0.39, p<0.001) and GC groups (0.98 ± 0.65, p<0.001) were significantly higher than in NUD group (0.46 ± 0.10). These results were also confirmed by IHC. A significantly higher percentage of MDSCs in patients with PUD (0.73 ± 0.19, p<0.001) and GC (0.73 ± 0.16, p<0.001) was also observed when compared to NUD group (0.46 ± 0.16). There was no difference in the percentages of these two cell types between the PUD and GC groups. The percentages of Tregs and MDSCs in patients with PUD and GC were not significantly correlated.

Conclusions: Both Tregs and MDSCs showed higher frequencies in PUD and GC. These results suggest that immune-modulation by the Tregs and MDSCs may play a role in the pathogenesis of PUD and GC.
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http://dx.doi.org/IJIv13i3A2DOI Listing
September 2016

Neuropeptide substance P and the immune response.

Cell Mol Life Sci 2016 11 17;73(22):4249-4264. Epub 2016 Jun 17.

Schepens Eye Research Institute, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts 02114.

Substance P is a peptide mainly secreted by neurons and is involved in many biological processes, including nociception and inflammation. Animal models have provided insights into the biology of this peptide and offered compelling evidence for the importance of substance P in cell-to-cell communication by either paracrine or endocrine signaling. Substance P mediates interactions between neurons and immune cells, with nerve-derived substance P modulating immune cell proliferation rates and cytokine production. Intriguingly, some immune cells have also been found to secrete substance P, which hints at an integral role of substance P in the immune response. These communications play important functional roles in immunity including mobilization, proliferation and modulation of the activity of immune cells. This review summarizes current knowledge of substance P and its receptors, as well as its physiological and pathological roles. We focus on recent developments in the immunobiology of substance P and discuss the clinical implications of its ability to modulate the immune response.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5056132PMC
http://dx.doi.org/10.1007/s00018-016-2293-zDOI Listing
November 2016

Frequency of γδ T Cells and Invariant Natural Killer T Cells in Helicobacter Pylori-infected Patients with Peptic Ulcer and Gastric Cancer.

Iran J Allergy Asthma Immunol 2015 Oct;14(5):493-501

Department of Immunology, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran AND Molecular and Cell Biology Research Center, Mazandaran University of Medical Sciences, Sari, Iran.

To clarify the effect of γδ T cells and invariant Natural Killer T (iNKT) cells in pathophysiology of dyspeptic disorders, number of these two cells in patients with non-ulcer dyspepsia (NUD), peptic ulcer disease (PUD), and gastric cancer (GC) were compared.Patients with dyspepsia were divided into three groups of NUD, PUD, and GC according to their endoscopic and histopathological examinations. Helicobacter pylori infection was diagnosed by rapid urease test and histopathology. The number of peripheral blood CD3+TCRγδ(+) T cells and CD3+Va24Ja18+ iNKT cells were determined by flow cytometry. Immunohistochemistry (IHC) was also used for identifying the TCRγδ+ cells.Forty two patients with NUD (31.6%), 44 with PUD (33.1%), and 47 with GC (35.3%) were included in the study. The frequency of CD3+TCRγδ(+) T cells in peripheral blood of patients with GC (2.71±0.25) was significantly lower than that in NUD (3.97±0.32, p<0.05) and PUD groups (3.87±0.32, p<0.05). However, there was no significant difference in CD3+TCRγδ(+) T cell percentage between the NUD and PUD groups. The frequency of TCRγδ(+) lymphocytes was significantly lower in tissue samples from patients with GC (4.81±0.53) than in NUD (11.09±1.09, p<0.0001) and PUD groups (11.11±1.01, p<0.0001). Also, we could not find any significant difference in the percentage of mucosal TCRγδ+ cells between the NUD and PUD groups. The results showed no significant difference in iNKT cells percentage among the three groups of patients.The results suggest that decreasing number of γδ T cells may be related to development and progression of gastric cancer.
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October 2015

Data supporting the design and evaluation of a universal primer pair for pseudogene-free amplification of HPRT1 in real-time PCR.

Data Brief 2015 Sep 6;4:384-9. Epub 2015 Jul 6.

Molecular and Cell Biology Research Center (MCBRC), Department of Immunology, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Mazandaran, Iran.

Hypoxanthine-guanine phosphoribosyltransferase 1 (HPRT1) is a common housekeeping gene for sample normalization in the quantitative reverse transcriptase polymerase chain (qRT-PCR). However, co-amplification of HPRT1 pseudogenes may affect accurate results obtained in qRT-PCR. We designed a primer pair (HPSF) for pseudogene-free amplification of HPRT1 in qRT-PCR [1]. We showed specific amplification of HPRT1 mRNA in some common laboratory cell lines, including HeLa, NIH/3T3, CHO, BHK, COS-7 and VERO. This article provides data supporting the presence and location of HPRT1 pseudogenes within human and mouse genome, and the strategies used for designing primers that avoid the co-amplification of contaminating pseudogenes in qRT-PCR. In silico analysis of human genome showed three homologous sequences for HPRT1 on chromosomes 4, 5 and 11. The mRNA sequence of HPRT1 was aligned with the pseudogenes, and the primers were designed toward 5' end of HPRT1 mRNA that was only specific to HPRT1 mRNA not to the pseudogenes. The standard curve plot generated by HPSF primers showed the correlation coefficient of 0.999 and the reaction efficiency of 99.5%. Our findings suggest that HPSF primers can be recommended as a candidate primer pair for accurate and reproducible qRT-PCR assays.
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http://dx.doi.org/10.1016/j.dib.2015.06.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4510554PMC
September 2015

VERO stable cell lines expressing full-length human epidermal growth factor receptors 2 and 3: platforms for subtractive phage display.

DNA Cell Biol 2015 Sep 29;34(9):573-8. Epub 2015 Jun 29.

1 Molecular and Cell Biology Research Center, Mazandaran University of Medical Sciences , Sari, Iran .

Cross-talk between human epidermal growth factor receptor 2 and 3 (HER2 and HER3) may potentially contribute to therapeutic resistance in human breast cancer. Subtractive phage display allows highly specific selection for antibody fragments directed against cells surface HER2 and HER3. The strategies to select conformation- and activation-specific antibodies against HER2 and HER3 require tightly regulated HER2 and HER3 expressing cells that allow controlled activation/inactivation of these receptors during panning procedures. To achieve this, first, we found that the VERO cell line is an appropriate cell line for heterogeneous expression of HER2 and HER3, and then we established a panel of VERO stable cell lines expressing high levels of HER2 and HER3 alone and in combination. We also showed that HER2 and HER3 expressed in VERO cells were biologically active and could form heterodimer following neuregulin1 treatment. The cell line established here not only provided platforms for phage display-based methods but also could be used in any HER-related studies.
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http://dx.doi.org/10.1089/dna.2015.2917DOI Listing
September 2015

Increased Expression of Two Alternative Spliced Variants of CD1d Molecule in Human Gastric Cancer.

Iran J Immunol 2015 Jun;12(2):129-40

Department of Immunology, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.

Background: CD1d presents glycolipid antigens to invariant natural killer T (iNKT) cells. The role of CD1d in the development of peptic ulcer and gastric cancer has not been revealed, yet.

Objective: To clarify the expression of alternatively spliced variants of CD1d in peptic ulcer and gastric cancer.

Methods: Patients with dyspepsia were selected and divided into three groups of non-ulcer dyspepsia (NUD), peptic ulcer disease (PUD), and gastric cancer (GC), according to their endoscopic and histopathological examinations. H. pylori infection was diagnosed by rapid urease test and histopathology. The expression levels of V2, V4, and V5 spliced variants of CD1d molecule were determined by quantitative Reverse Transcriptase PCR.

Results: Relative gene expression levels of V4 were higher in GC patients (n=37) than those in NUD (n=49) and PUD (n=51) groups (p<0.05 and p<0.01, respectively). Moreover, GC patients showed higher expression levels of V5 compared to NUD and PUD groups (p<0.001 and p<0.001, respectively). Positive correlation coefficients were attained between V4 and V5 expression in patients with PUD (r=0.734, p<0.0001) and GC (r=0.423, p<0.01), but not in patients with NUD. Among NUD patients, the expression levels of V4, but not V5, were higher in H. pylori-positive patients than in H. pylori-negative ones (p<0.01).

Conclusion: Collectively, both membrane-bound (V4) and soluble (V5) isoforms of CD1d were over-expressed in gastric tumor tissues, suggesting that they are involved in anti-tumor immune responses.
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http://dx.doi.org/IJIv12i2A5DOI Listing
June 2015

Pseudogene-free amplification of HPRT1 in quantitative reverse transcriptase polymerase chain reaction.

Anal Biochem 2015 Sep 4;485:46-8. Epub 2015 Jun 4.

Molecular and Cell Biology Research Center (MCBRC), Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Mazandaran, Iran.

Quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) provides a powerful tool for precise gene expression analysis. The accuracy of the results highly depends on careful selection of a reference gene for data normalization. HPRT1 (hypoxanthine phosphoribosyl transferase 1) is a frequently used housekeeping gene for normalizing relative expression values. However, the existence of processed pseudogenes for HPRT1 might interfere with reliable results obtained in qRT-PCR due to amplification of unintended products. Here, we designed a primer pair for pseudogene-free amplification of HPRT1 in qRT-PCR. We demonstrate that this primer pair specifically amplified HPRT1 messenger RNA (mRNA) sequence while avoiding coamplification of the pseudogenes.
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http://dx.doi.org/10.1016/j.ab.2015.05.021DOI Listing
September 2015

Role of HER2 in brain metastasis of breast cancer: a systematic review and meta-analysis.

Asian Pac J Cancer Prev 2015 ;16(4):1431-4

Molecular and Cell Biology Research Center, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran E-mail :

Background: Breast cancer is one of the most common cancers among women worldwide and the HER2 receptor plays an important role in its development and progression. This systematic review aimed to summarize the role of HER2 in brain metastasis in patients with breast cancer.

Materials And Methods: We conducted a literature search by advanced search in title field using the Scopus, Pubmed, and Google scholar databases until the end of June 2014. With metastasis, metastatic, HER2, brain, and breast cancer, as terms of search we selected 31 articles, which were reviewed by two independent and blinded expert reviewers. The studies were first selected according to their titles and abstracts. Quality of the studies were then assessed using the STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) protocol for observational studies and CONSORT(Consolidation of Standards for Reporting Trials) protocol for clinical trials. For statistical analyses, we used STATA, version 11.0 software. Forest and funnel diagrams were drawn and for heterogeneity, index was also considered. Also we used meta regression analysis.

Results: Finally, we reviewed 10 studies. The prevalence of brain metastasis in HER2- positive breast cancer patients was 24.9%. There was publication bias in the reviewed studies. Meta regression analysis showed that follow up time had no significant effect (p=0.396) on the prevalence of brain metastasis.

Conclusions: The results showed a high prevalence of brain metastasis in HER2 positive breast cancer patients.
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http://dx.doi.org/10.7314/apjcp.2015.16.4.1431DOI Listing
December 2015

Aqueous humor and serum concentrations of soluble MICA and MICB in glaucoma patients.

Iran J Immunol 2014 Dec;11(4):275-81

Department of Ophthalmology, Bou Ali Sina Hospital, Mazandaran University of Medical Sciences, Sari, Iran,

Background: Immune reactions have been reported to be involved in the destruction of retinal ganglion cells (RGCs) in glaucoma.

Objective: To investigate the role of major histocompatibility complex class I-related chain A and B (MICA and MICB) molecules in the pathogenesis of glaucoma.

Methods: Aqueous humor and serum samples from 15 glaucoma patients and 45 patients with cataract, undergoing ocular surgery, were obtained. The concentrations of MICA and MICB molecules in all samples were measured using ELISA.

Results: Both MICA and MICB concentrations were higher in the aqueous humor of patients with glaucoma compared to those with cataract (p=0.013 and p=0.004, respectively); however, in the serum samples, no significant differences were observed.

Conclusions: Increased intraocular pressure may be associated with increased expression of the MICA and MICB molecules, which could initiate the destruction of RGCs and consequent development of glaucoma.
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http://dx.doi.org/IJIv11i4A6DOI Listing
December 2014

Expression levels of vascular endothelial growth factors a and C in patients with peptic ulcers and gastric cancer.

J Gastric Cancer 2014 Sep 30;14(3):196-203. Epub 2014 Sep 30.

7 Department of Immunology, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran.

Purpose: Vascular endothelial growth factor (VEGF) is one of the most important growth factors for metastatic tumors. To clarify the role of VEGF-A and C in patients with peptic ulcer disease (PUD) or gastric cancer (GC), we evaluated the expression levels of these two molecules. We also analyzed the effect of Helicobacter pylori infection on VEGF-A and C expression levels.

Materials And Methods: PATIENTS WITH DYSPEPSIA WHO NEEDED DIAGNOSTIC ENDOSCOPY WERE SELECTED AND DIVIDED INTO THREE GROUPS: non-ulcer dyspepsia (NUD), PUD, and GC, according to their endoscopic and histopathological results. Fifty-two patients with NUD, 50 with PUD, and 38 with GC were enrolled in this study. H. pylori infection was diagnosed by the rapid urease test. After RNA extraction and synthesis of cDNA, the expression levels of VEGF-A and C were determined by quantitative reverse transcriptase polymerase chain reaction.

Results: The VEGF-C expression level in the PUD and GC groups was significantly higher than that in the NUD group. Moreover, the VEGF-A expression level in the PUD and GC groups was higher than in the NUD group, although the differences were not statistically significant. Significant positive correlations were also observed between the expression levels of these two molecules in the PUD and GC groups. In addition, the expression levels of these two molecules were higher in H. pylori positive patients with PUD or GC than in H. pylori negative patients of the same groups; however, these differences did not reach statistical significance.

Conclusions: Up-regulation of VEGF-C expression during gastric mucosal inflammation may play a role in the development of peptic ulcers or GC.
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http://dx.doi.org/10.5230/jgc.2014.14.3.196DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4199887PMC
September 2014

Toll like receptor-4 896A/G gene variation, a risk factor for migraine headaches.

Iran J Immunol 2012 Sep;9(3):159-67

Neurology Ward, Department of Internal Medicine, Buali Hospital, Sari, Iran, e-mail:

Background: The pathogenesis of migraine involves immune-mediated mechanisms in the vascular endothelium. Toll like receptor 4 (TLR-4) is a signaling receptor of innate immunity which plays a role in various neuropathologies related to neuron inflammation.

Objective: This case/control study is aimed to investigate whether TLR-4 896A/G variation is related to migraine headaches in an Iranian population.

Methods: A total of 170 migraine patients (130 females, mean age 33.24 ± 11 years) and 170 age, sex, and ethnicity matched healthy controls (118 females, mean age of 31 ± 10 years) were recruited. Genotyping was carried out using the tetra primer amplification refractory mutation system (ARMS)-PCR.

Results: The frequency of G allele was higher in migraine patients than the controls (15% vs. 4.7%; p<0.0001). Interestingly, the distribution of heterozygous 896A/G genotype statistically differed between migraineurs and controls (25.3% vs. 8.2%, p=0.00002, OR 3.87, 95% CI; 2.02-7.4). Multivariate logistic regression analysis indicated that G allele in affected female migraineurs is an independent factor associated with increased risk of migraine (OR 3.2, 95% CI 1.23-8.24, p=0.01).

Conclusion: Our results showed TLR-4 polymorphism as a genetic risk factor for migraine. However, further studies in different populations are required to elucidate the precise role of TLR-4 896A/G mutation in susceptibility to migraine.
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http://dx.doi.org/IJIv9i3A2DOI Listing
September 2012

Decreased levels of soluble Toll-like Receptor 2 in patients with asthma.

Rep Biochem Mol Biol 2012 Oct;1(1):30-6

Immunobiochemistry lab, Immunology Research Center, Bu-Ali Research Institute, Mashhad, Iran.

Background: Recently, reports have indicated a role for the membrane form of Toll-like Receptor 2 (TLR2) in asthma pathogenesis. In this study we examined soluble TLR2 levels in serum and sputum of asthmatic and healthy subjects.

Methods: Serum and sputum samples were obtained from 33 asthmatic and 19 healthy subjects. The asthmatics were classified into four groups according to the Global Initiative for Asthma. A sandwich ELISA was developed to measure soluble TLR2 (sTLR2) in serum and sputum. TLR2 mRNA expression was determined by semi-quantitative RT-PCR of all sputum samples.

Results: The mean sTLR2 levels from serum and sputum of asthmatics were significantly lower than those from healthy subjects. Moreover, sTLR2 concentration decreased concomitantly with asthma severity. The differences observed, however, were not statistically significant. TLR2/GAPDH mRNA of sputum leukocytes was also significantly lower in asthmatics than in healthy subjects.

Conclusion: This study demonstrated for the first time thatsTLR2 levels are lower in serum and sputum samples from asthmatic than from healthy subjects, and this could be an indicator of TLR2 expression. We also found that sTLR2 concentration in serum decreased concomitantly with an increase of asthma severity clinical score .
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4757078PMC
October 2012

Clinical and laboratory investigation of oral allergy syndrome to grape.

Iran J Allergy Asthma Immunol 2012 Jun;11(2):147-55

Allergy Research Center, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

Oral allergy syndrome (OAS) is occasionally observed following consumption of raw fruits in allergic adults. Since this phenomenon was commonly reported in Khorasan province of Iran; we intended to check if common diagnostic tests could be applied for differential diagnosis of OAS to grapes.IgE reactivity of 84 patients with OAS to grape and 34 patients with OAS to other fruits were analyzed by in vivo and in vitro methods, and the results were compared with those of controls. The patients underwent skin prick test (SPT) with common allergic pollen extracts as well as grape extract. The specific IgE level to grape proteins was determined by an indirect ELISA. The correlation of SPT results with ELISA and western blotting patterns was checked by statistical methods. The results showed a significant correlation of grape SPT diameters with grape specific IgE levels. Furthermore, a significant association of grape SPT results with IgE immunoreactivity of a 10 kDa grape protein, probably lipid transfer protein (LTP) was prominent. Immunoreactivity of other proteins was linked with mild clinical symptoms. The study showed a significant correlation of grape SPT results with grape total extract, as well as its 10 kDa component's IgE reactivity. The results suggested that OAS to grape should not be considered as a main criterion in diagnosis of grape allergy and a combination of grape SPT results with evaluation of IgE reactivity to grape 10 kDa allergen should be considered to achieve a more reliable grape allergy diagnosis.
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http://dx.doi.org/011.02/ijaai.147155DOI Listing
June 2012