Publications by authors named "Ali-Akbar Delbandi"

19 Publications

  • Page 1 of 1

Association Between Vitamin D Receptor (VDR) and Vitamin D Binding Protein (VDBP) Genes Polymorphisms to Endometriosis Susceptibility in Iranian Women.

Reprod Sci 2021 May 4. Epub 2021 May 4.

Department of Immunology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.

Endometriosis is a chronic inflammatory disease that has been reported to be associated with immune system dysfunction. On the other hand, the effect of Vitamin D as an immune modulator and its relation with several autoimmune and inflammatory diseases has been previously investigated. Moreover, several studies have reported the polymorphisms of VDR and VDBP genes can change the functions of these molecules. Therefore, these polymorphisms may be influential on endometriosis pathogenesis. In this study, we aimed at evaluating the association between VDR gene (FokI (F/f), BsmI (B/b), ApaI (A/a), TaqI (T/t)), and VDBP gene (GC*1S, GC*1F, and GC*2) polymorphisms with endometriosis in Iranian women population. This case-control study was performed on 120 women with endometriosis and 110 healthy women. ARMS-PCR and PCR-RFLP methods were used to inspect polymorphisms in VDR and VDBP genes, respectively. Based on the results, there was no statistically significant difference between the cases with endometriosis and control subjects in terms of genotypes and allele frequencies of VDR and VDBP gene polymorphisms. These data suggest that VDR and VDBP gene polymorphisms may have no role in endometriosis susceptibility in Iranian women.
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http://dx.doi.org/10.1007/s43032-021-00598-zDOI Listing
May 2021

The effects of resveratrol on the expression of VEGF, TGF-β, and MMP-9 in endometrial stromal cells of women with endometriosis.

Sci Rep 2021 Mar 15;11(1):6054. Epub 2021 Mar 15.

Department of Immunology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.

Resveratrol is a phytochemical with anti-angiogenic, anti-inflammatory, and antioxidant properties. The present study has evaluated the effect of resveratrol on the expression of vascular endothelial growth factor (VEGF), transforming growth factor-β (TGF-β) and matrix metalloproteinase-9 (MMP-9) as factors related to endometriosis progression. Thirteen eutopic (EuESCs) and 8 ectopic (EESCs) endometrial stromal cells from women with endometriosis and 11 control endometrial stromal cells (CESCs) were treated with resveratrol (100 µM) for 6, 24 and 48 h. The gene and protein expression levels of VEGF, TGF-β, and MMP-9 were measured using real-time PCR and ELISA methods, respectively. Results showed that the basal gene and protein expression of VEGF and MMP-9 were higher in EESCs compared to EuESCs and CESCs (P < 0.01 to  < 0.001 and P < 0.05 to  < 0.01 respectively). Also, resveratrol treatment decreased the gene and protein expression of VEGF and MMP-9 in EuESCs, EESCs and CESCs (P < 0.05 to  < 0.01 and P < 0.05 to  < 0.01 respectively) and gene and protein expression of TGF-β in EESCs and EuESCs (P < 0.05 to  < 0.01). The effect of resveratrol in reduction of VEGF gene expression was statistically more noticeable in EESCs compared to EuESCs and CESCs (P < 0.05). According to the findings, resveratrol may ameliorate endometriosis progression through reducing the expression of VEGF, TGF-β, and MMP-9 in endometrial stromal cells (ESCs).
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http://dx.doi.org/10.1038/s41598-021-85512-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7961000PMC
March 2021

Evaluation of Serum Immunoreactivity to Common Indigenous Iranian Inhalation and Food Allergens in Patients with Meniere's Disease.

Immunol Invest 2021 Jan 8:1-10. Epub 2021 Jan 8.

Skull Base Research Center, The Five Senses Health Institute, Iran University of Medical Sciences, Tehran, Iran.

: A few studies investigated the relationship between allergy and Meniere disease considering complete allergen panel. We aimed to evaluate the serum immunoreactivity in patients with Meniere's disease (MD) compared with healthy people according to common indigenous Iranian inhalation and food allergens.: Thirty-nine patients with MD referred to Rasoul Akram Hospital (Tehran, Iran) were evaluated and compared with a 41 membered control group. A panel of common inhalation and food allergens (using an immunoblotting method), as well as total immunoglobulin E (IgE) level (using the sandwich enzyme-linked immunosorbent assay method), were checked on the patients' serum.: The mean total IgE level was 193.85 ± 175.43 IU/ml in the patients with MD and 117.61 ± 138.05 IU/ml in the control group, which was significantly higher than the other subjects in the control group ( = .016). There was a significant difference between the two groups regarding inhalation allergens such as; sweet vernal grass, cultivated rye, cultivated oat, Russian thistle, goosefoot, and rough pigweed ( = .01-0.038). Patients with MD reported more reactive to food allergens such as; rye flour, hazelnut, pepper, citrus mix 2, potato, strawberry, and celery allergens. There was a significant relationship between Meniere and serum immunoreactivity to inhalation and food allergens (both = .001).: Serum total IgE level in patients with MD (in both inhalation and food allergens groups) was higher than the control group, and there was a relationship between MD and immunoreactivity to common indigenous inhalation and food allergens of Iran.
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http://dx.doi.org/10.1080/08820139.2020.1869252DOI Listing
January 2021

Vitamin D deficiency as a risk factor for endometriosis in Iranian women.

J Reprod Immunol 2021 02 17;143:103266. Epub 2020 Dec 17.

Department of Immunology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran. Electronic address:

Purpose: Vitamin D (Vit D), as an immunomodulator, has been hypothesized to play a critical role in the pathogenesis of endometriosis. Thus, in this study, we evaluated whether there is an association between 25-hydroxyvitamin D [25(OH)D] and susceptibility to endometriosis in Iranian women.

Methods: Women at reproductive age, including 56 healthy women and 54 patients with endometriosis, were enrolled in the study. Serum levels of 25(OH)D, calcium, parathyroid hormone (PTH), and peritoneal fluid (PF) levels of 25(OH)D were assessed.

Results: The serum and PF levels of 25(OH)D in the patients with endometriosis were significantly lower than the control group (P = 0.001 and P = 0.03, respectively). Subjects with serum levels of 25(OH)D lower than 20 ng/mL had a 2.7 times higher risk of endometriosis than people with 25(OH)D serum levels higher than 20 ng/mL (non-deficient) (OR = 2.7, 95 % confidence interval: 1.24-5.80, P = 0.01). The serum levels of calcium and PTH were significantly lower and higher in patients with endometriosis compared with controls, respectively (P < 0.001, P = 0.02, respectively). Also, the serum levels of 25(OH)D were lower in stages I-II endometriosis than stage III-IV; however, no significant difference was observed.

Conclusion: Our findings showed that people with Vit D deficiency are at higher risk of endometriosis.
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http://dx.doi.org/10.1016/j.jri.2020.103266DOI Listing
February 2021

Resveratrol treatment reduces expression of MCP-1, IL-6, IL-8 and RANTES in endometriotic stromal cells.

J Cell Mol Med 2021 Jan 15;25(2):1116-1127. Epub 2020 Dec 15.

Department of Immunology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.

Endometriosis is an inflammatory disease affecting reproductive-aged women. Immunologic disturbance, as well as inflammation, have crucial roles in the pathogenesis of endometriosis. In this study, we evaluated the effects of resveratrol treatment on expression of monocyte chemotactic protein-1 (MCP-1), interleukin-6 (IL-6), IL-8, and regulated upon activation, normal T cell expressed and secreted (RANTES) in endometrial stromal cells from patients with endometriosis compared with non-endometriotic controls. Thirteen eutopic (EuESCs) and nine ectopic (EESCs) endometrial stromal cells from endometriotic patients as well as eleven endometrial stromal cells from non-endometriotic controls (CESCs) were treated with resveratrol (100 μmol/L) or ethanol, and gene and/or protein expression of MCP-1, IL-6, IL-8 and RANTES was examined at 6, 24 and 48 hours following treatment in the cells from all origins. Resveratrol treatment significantly reduced gene and protein expression of MCP-1, IL-6, and IL-8 in EuESCs and EESCs compared with CESCs (P < .05-.001, P < .05-.001 and P < .05-<.01, respectively), and this reduction was more noticeable in EESCs than EuESCs (P < .05-<.001). Besides, resveratrol treatment significantly reduced RANTES protein expression in EESCs in all time intervals (P < .05). Resveratrol treatment significantly reduced the expression of MCP-1, IL-6, IL-8 and RANTES in EESCs.
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http://dx.doi.org/10.1111/jcmm.16178DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7812293PMC
January 2021

The Effects of Resveratrol Treatment on Bcl-2 and Bax Gene Expression in Endometriotic Compared with Non-Endometriotic Stromal Cells.

Iran J Public Health 2020 Aug;49(8):1546-1554

Department of Nutrition, School of Public Health, Iran University of Medical Sciences, Tehran, Iran.

Background: We aimed to examine resveratrol effects on gene expression of Bcl-2, Bax and Bcl-2/Bax ratio in endometrial stromal cells derived from women with and without endometriosis.

Methods: Endometrial tissues were obtained from 40 endometriotic patients and 15 non-endometriotic controls undergoing laparoscopic surgery or hysterectomy in the gynecology ward of Rassoul Akram Hospital, Tehran, Iran from 2015 to 2017. After the enzymatic digestion, eutopic (EuESCs) and ectopic (EESCs) endometrial stromal cells from patients with endometriosis as well as endometrial stromal cells from non-endometriotic controls (CESCs) were treated with or without resveratrol (100 μM) and the levels of Bcl-2, Bax and Bcl-2/Bax gene expression ratio in the cells from all origins were examined at 6, 24 and 48 h post-treatment by real-time PCR.

Results: Resveratrol treatment increased Bcl-2 expression in CESCs at 24 and 48 h and in EuESCs at 48 h (<0.05), but had no significant effects on the expression of this gene in EESCs. On the other hand, resveratrol treatment increased Bax expression in EuESCs at 6 h and decreased its expression in EESCs at 48 h (<0.05). Regarding the Bcl-2/Bax gene expression ratio, resveratrol treatment increased Bcl-2/Bax gene expression ratio in CESCs and EuESCs at 48 h (<0.01). However, this treatment had no significant differential effect on Bcl-2 and Bcl-2/Bax gene expression ratio between CESCs and EuESCs at 48 h.

Conclusion: Resveratrol treatment significantly increased Bcl-2/Bax gene expression ratio in EuESCs and CESCs but had no significant effect in EESCs.
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http://dx.doi.org/10.18502/ijph.v49i8.3900DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7554380PMC
August 2020

The Diagnostic Accuracy of Combined Enolase/Cr, CA125, and CA19-9 in the Detection of Endometriosis.

Biomed Res Int 2020 2;2020:5208279. Epub 2020 Sep 2.

Department of Obstetrics and Gynecology, Kiel School of Gynaecological Endoscopy, University Hospital Schleswig Holstein, Campus Kiel, Arnold-Heller-Str. 3, Haus C, 24105 Kiel, Germany.

Background: The present study was designed to verify the accuracy of the noninvasive biomarkers enolase/Cr, CA125, and CA19-9 as a clinical diagnostic tool for the detection of endometriosis.

Methods: A cross-sectional study was performed at Rasool-e-Akram Hospital affiliated to Iran University of Medical Sciences, Tehran, Iran, from April 2015 to April 2018. Eighty-six women were scheduled to undergo laparoscopy due to chronic pelvic pain, infertility, pelvic mass, and abnormal uterine bleeding. Serum and urine samples of all patients were collected preoperatively. Serum levels of CA125 and CA19-9, and urine levels of enolase-1 were measured. Serum levels of CA125 and CA19-9 were determined by the electrochemiluminescence method (ECL). Urinary enolase-1 was measured by the ELISA method.

Result: Serum levels of CA125 and CA19-9 were significantly higher in the endometriosis group than in controls ( < 0.001, = 0.004, respectively). Levels of enolase I and enolase/Cr were higher in patients with endometriosis, but the differences were not statistically significant. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of combined enolase/Cr, CA125, and CA19-9 were 65%, 66.6%, 71%, and 60.1%, respectively. The positive likelihood ratio (PLR) and negative likelihood ratio (NLR) of combined enolase/Cr, CA125, and CA19-9 was 1.94 and 0.52, respectively. The area under the ROC curve for enolase/Cr + CA125 + CA19 - 9 was 0.675 (95% confidence interval 0.573-0.710).

Conclusion: The present study revealed that concurrent measurement of enolase-1, CA125, and CA19-9 might be a valuable noninvasive test for the identification of endometriosis.
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http://dx.doi.org/10.1155/2020/5208279DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7545435PMC
May 2021

Immunomodulatory effects of vitamin D3 on gene expression of MDGF, EGF and PDGFB in endometriosis.

Reprod Biomed Online 2020 Nov 26;41(5):782-789. Epub 2020 May 26.

Immunology Research Center, Immunology and Infectious Disease Institute, Iran University of Medical Sciences, Tehran, Iran; Department of Immunology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran. Electronic address:

Research Question: Endometriosis, an inflammatory disease, is assumed to be associated with an increased production of growth-related cytokines. Based on the emerging immunomodulatory role of vitamin D3 in different inflammatory conditions, this study aimed to examine its modulatory effect on the expression levels of the genes for platelet-derived growth factor-B (PDGFB), monocyte/macrophage-derived growth factor (MDGF, also known as PPBP) and epidermal growth factor (EGF) in peritoneal fluid mononuclear cells (PFMC) in women with and without endometriosis.

Design: PFMC from 10 women with endometriosis and 10 control participants were treated with vitamin D3.The gene expression levels of PDGFB, MDGF and EGF were measured 6, 24 and 48 h following vitamin D3 administration using real-time PCR.

Results: Gene expression levels of EGF and PDGFB were higher in the PFMC of women with endometriosis than the control group (P = 0.006, P < 0.001, respectively). Although MDGF expression showed an increase in the endometriosis group compared with non-endometriotic controls, no significant difference was found. Vitamin D3 significantly decreased EGF expression at 6, 24 and 48 h (P < 0.001, P < 0.001 and P = 0.007, respectively), MDGF at 24 and 48 h (P < 0.001 and P = 0.009, respectively) and PDGFB at 6 h (P = 0.047) in the endometriosis group. Vitamin D3 treatment had no significant effect on expression of the genes in the PFMC of non-endometriotic women.

Conclusions: The study concluded that PDGFB and EGF gene expression increases in endometriosis, and vitamin D3 could markedly decrease this expression, suggesting its therapeutic potential in endometriosis.
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http://dx.doi.org/10.1016/j.rbmo.2020.05.013DOI Listing
November 2020

The effect of smoking on latent tuberculosis infection susceptibility in high risk individuals in Iran.

J Immunoassay Immunochem 2020 Sep 16;41(5):885-895. Epub 2020 Aug 16.

Department of Immunology, School of Medicine, Iran University of Medical Sciences , Tehran, Iran.

Tuberculosis has been declared as a global emergency. Latent tuberculosis infection (LTBI) is a state in which host immunity cannot completely eradicate . Cigarette smoke increases the risk of respiratory infections, such a TB, as it has adverse effects on respiratory immune function. In this cross-sectional study, which was performed from 2016 to 2017, 31 patients with newly diagnosed lung cancer, 63 Chronic obstructive pulmonary disease (COPD), 46 with problems in respiratory system, and 40 healthy subjects were studied. Demographic data of all subjects were recorded a questionnaire. IGRAs (Interferon-γ release assays) were used to determine LTBI. We showed that smoking has significant odds ratio for COPD patients (OR: 4.58, 95% CI: 1.93-10.87). Also, the concordance of smoking with COPD (OR: 22, 95% CI: 2.7-179.2), lung cancer (OR: 10, 95% CI: 1.03-97), and other respiratory diseases (OR: 4.54, 95% CI: 1.93-10.87) is a significant risk factor for the presence of LTBI whereas the existence of LTBI in the study groups did not show any significant odds ratio. This study is the first to analyze the relationship between smoking in patients with respiratory diseases and LTBI susceptibility in Iran by IGRAs, which proposes cigarette smoking as a powerful risk factor for LTBI.
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http://dx.doi.org/10.1080/15321819.2020.1806075DOI Listing
September 2020

Antifungal Activity of Capric Acid, Nystatin, and Fluconazole and Their Interactions Against Isolates from Neonatal Oral Thrush.

Assay Drug Dev Technol 2020 May/Jun;18(4):195-201. Epub 2020 May 11.

Department of Medical Parasitology and Mycology, School of Medicine, Iran University of Medical Science, Tehran, Iran.

Due to the increasing resistance of various species to azole drugs, particularly fluconazole, it would be of significant importance to look for alternative therapies. The aim of this study was to investigate the antifungal activity of capric acid and its interactions with nystatin and fluconazole against isolates. A total of 40 isolates (, 36; , 2; , 1; , 1) collected from the oral cavity of neonates with oropharyngeal candidiasis and a reference strain of (ATCC 10231) were used in this study. Antifungal activity of capric acid and two comparator antifungal drugs, namely fluconazole and nystatin, was tested according to CLSI M27-A3/M60 method. The interaction between capric acid with fluconazole and nystatin was determined following a checkerboard method and results were interpreted using fractional inhibitory concentration index. Nystatin had the lowest minimum inhibitory concentrations (range, 0.125-8 μg/mL; geometric mean [GM], 0.6229 μg/mL) followed by fluconazole (range, 0.5-16 μg/mL; GM, 1.9011 μg/mL) and capric acid (range, 128-2,048 μg/mL; GM, 835.9756 μg/mL). When tested in combination, capric acid with fluconazole demonstrated synergistic, indifferent, and antagonistic interactions in 3 (7.317%), 24 (58.536%), and 14 (34.146%) cases, respectively. For combination of capric acid with nystatin, synergistic, indifferent, and antagonistic interactions were observed in 1 (2.439%), 19 (46.341%), and 21 (51.219%) cases, respectively. All cases of synergistic interactions were against resistant or susceptible dose-dependent isolates. Fluconazole, nystatin, and capric acid seem to be more effective when they are used alone compared with their combination. However, their combination might be effective on resistant isolates.
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http://dx.doi.org/10.1089/adt.2020.971DOI Listing
May 2020

Human platelet antigen 1-6, 9 and 15 in the Iranian population: An anthropological genetic analysis.

Sci Rep 2020 05 4;10(1):7442. Epub 2020 May 4.

Department of Immunology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.

Human platelet antigens (HPAs) are membranous glycoproteins considered as alloantigens due to their polymorphisms. HPA-incompatibility in multiple pregnancies or blood transfusion can induce the development of alloantibodies leading to thrombocytopenia. The frequency of HPAs varies among populations, so that deep knowledge of HPA frequencies will help us to reduce those incompatibilities. Herein, we studied the allele and genotype frequencies of HPA1-6, HPA9, and HPA15 among the Iranians with intra- and inter-populations analyses on 36 worldwide populations with diverse ethnicities. The analysis shows that the HPA2 and HPA5 have the greatest differences in genotype distribution between the Iranians and other nations, although similar to other populations, the sole allele found in HPA4, 6, and 9 is "a". Despite other HPAs, the most frequent allele in HPA15 is "b", which is also abundant in HPA3. Hierarchical clustering indicates the highest degree of global similarity in HPA genotype frequency among Iranian, Argentinian, Brazilian, and German Turkish populations. Our findings can be applied to decrease the risk of alloimmunizations and platelet disorders, especially in neonates.
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http://dx.doi.org/10.1038/s41598-020-64469-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7198494PMC
May 2020

Higher frequency of circulating, but not tissue regulatory T cells in patients with endometriosis.

J Reprod Immunol 2020 06 18;139:103119. Epub 2020 Mar 18.

Reproductive Immunology Research Center, Avicenna Research Institute, ACECR, Tehran, PO Box: 19615-1177, Iran; Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran. Electronic address:

Background: Endometriosis is one of the most common chronic gynecological disorders affecting women at reproductive age. Dysregulation of immune cells, including regulatory T (Treg) cells has contributed to the growth of ectopic lesion in patients with endometriosis.

Objective: The present study investigated the frequency of Tregs in peripheral blood and the expression of Foxp3 in eutopic and ectopic endometriotic tissues in women with and without endometriosis.

Materials And Methods: Peripheral blood mononuclear cells (PBMCs) and eutopic and ectopic endometriotic tissues were obtained from 23 endometriotic and 20 non-endometriotic control women. The frequency of Treg cells in PBMCs was measured using flowcytometry and the expression of Foxp3 in eutopic and ectopic endometriotic tissues was determined by real-time PCR, western blotting and immunohistochemistry.

Result: The frequency of circulating Tregs was significantly higher in endometriotic patients compared with non-endometriotic controls (P < 0.01). The mRNA and protein expression of Foxp3 in eutopic and ectopic endometriotic tissues had no significant differences between the two study groups.

Conclusion: Higher frequency of circulating Tregs in patients with endometriosis compared with controls may be considered as a compensatory mechanism to regulate the inflammatory condition in this disease.
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http://dx.doi.org/10.1016/j.jri.2020.103119DOI Listing
June 2020

Evaluation of apoptosis and angiogenesis in ectopic and eutopic stromal cells of patients with endometriosis compared to non-endometriotic controls.

BMC Womens Health 2020 01 6;20(1). Epub 2020 Jan 6.

Reproductive Immunology Research Center, Avicenna Research Institute, ACECR, Tehran, Iran.

Background: Endometriosis is a chronic, painful, and inflammatory disease characterized by extra-uterine growth of endometrial tissues. Increased angiogenesis and resistance to apoptosis have been suggested to be involved in pathogenesis and development of endometriosis. The objective of this study was to examine apoptosis potential and angiogenesis contribution of eutopic (EuESCs) and ectopic (EESCs) endometrial stromal cells in patients with endometriosis compared to endometrial stromal cells from non-endometriotic controls (CESCs).

Methods: Stromal cells were isolated by enzymatic digestion of ectopic (n = 11) and eutopic (n = 17) endometrial tissues from laparoscopically-confirmed endometriotic patients. Endometrial stromal cells of 15 non-endometriotic patients served as control. Following cell characterization by immunofluorescent staining and flow cytometry using a panel of antibodies, the total RNA was isolated from the cultured cells, and analyzed for the expression of genes involved in apoptosis (Bcl-2, Bcl-xL, Bax, and caspase-3) and angiogenesis [vascular endothelial growth factor-A (VEGF-A) and hepatocyte growth factor (HGF)] by Real-time PCR.

Results: Significantly higher gene expression levels of Bcl-2 and Bcl-xL were found in EESCs compared with EuESCs and CESCs (p < 0.01). The gene expression of Bax in EESCs, EuESCs, and CESCs was not statistically significant. Furthermore, EuESCs exhibited a significantly lower caspase-3 gene expression compared with CESCs (p < 0.01) or EESCs (p < 0.05). Regarding angiogenesis, VEGF-A gene expression in EESCs (p < 0.001) and EuESCs (p < 0.05) were significantly higher compared with those of CESCs. EESCs exhibited a significantly higher HGF gene expression compared with EuESCs (p < 0.05).

Conclusions: These findings suggest reduced propensity to apoptosis and increased angiogenesis potential of EESCs, which may be involved in pathogenesis of endometriosis.
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http://dx.doi.org/10.1186/s12905-019-0865-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6945780PMC
January 2020

Priming TLR3 and TLR4 in human adipose- and olfactory mucosa-derived mesenchymal stromal cells and comparison of their cytokine secretions.

Cytotechnology 2020 Feb 2;72(1):57-68. Epub 2020 Jan 2.

Department of Immunology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.

Mesenchymal stromal cells (MSCs) have potent immunomodulatory abilities to regulate most of the immune cells. Not only the tissue origin of MSCs can affect their functions, but also their microenvironment can strongly influence their biology, particularly through toll-like receptors (TLR)/ligands interaction. In the present study, we compared MSCs derived from two different sources, i.e. human olfactory ecto-mesenchymal stem cells (OE-MSCs) and adipose tissue (AT-MSCs), in terms of their immunosuppressive effects before and after TLR3 and TLR4 stimulation through low-level and short-term TLR-priming protocol. After isolation and characterization of OE-MSCs and AT-MSCs, flow cytometry analyses were used to assess the expression of TLR3, TLR4 by MSCs. Secretion and expression levels of immune-related genes were analyzed using ELISA and RT-qPCR techniques. Based on the results, the proliferation potential of OE-MSCs was significantly higher than that of AT-MSCs. The gene expression and also protein levels of both TLR3 and TLR4 were significantly higher in OE-MSCs, compared to AT-MSCs. Among the examined cytokines and chemokines, OE-MSCs exhibited significantly higher levels of CCL5, IL-8, and TGF-β production, in comparison with AT-MSCs. However, IL-6 secretion by AT-MSCs was considerably more than that by OE-MSCs. OE-MSCs were only affected by the TLR4 ligand, and IL-8 and IL-6 production levels increased after LPS treatment. However, only IL-8 significantly increased after adding LPS or Poly (I:C) to the AT-MSC media. According to the obtained data, OE-MSCs exhibited a higher proliferative potential and greater expression levels of TLR3 and TLR4 genes, compared to AT-MSCs. However, unlike AT-MSCs, the expression of TLR3 by OE-MSCs was nonfunctional. Finally, based on our findings, OE-MSCs have a stronger secretion of immunosuppressive cytokines both before and after LPS or PIC treatment, compared to AT-MSCs.
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http://dx.doi.org/10.1007/s10616-019-00357-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7002628PMC
February 2020

Disturbed Transcription of TLRs' Negative Regulators and Cytokines Secretion among TLR4- and 9-Activated PBMCs of Agammaglobulinemic Patients.

Immunol Invest 2019 Nov 11;48(8):860-874. Epub 2019 Jun 11.

Immunology Research Center (IRC), Institute of Immunology and Infectious Diseases, Iran University of Medical Sciences , Tehran , Iran.

Toll-like receptors (TLRs) are inevitable elements for immunity development and antibody production. TLRs are in close interaction with Bruton's tyrosine kinase which has been found mutated and malfunctioned in the prototype antibody deficiency disease named X-linked agammaglobulinemia (XLA). TLRs' ability was evaluated to induce transcription of TLR-negative regulators, including suppressor of cytokine signaling 1 (SOCS1), interleukin-1 receptor-associated kinase 3 (IRAK-M), tumor necrosis factor alpha-induced protein 3 (TNFAIP3, A20), and Ring finger protein 216 (RNF216), and Tumor necrosis factor-α (TNF-α) and Interferon-α (IFN-α) production via Lipopolysaccharides (LPS) and CpG-A oligodeoxynucleotides (CpG-A ODN). Measured by TaqMan real-time polymerase chain reaction (PCR), meaningfully increased transcripts of SOCS1 and RNF216 were found in XLA peripheral blood mononuclear cells (PBMCs). Also, TLR inductions of XLA have led to similar downregulations in the regulator's transcription which was different from that in healthy donors. Cytokine measurement by enzyme-linked immunosorbent assay (ELISA) revealed a significant lower TNF-α production both before and after LPS. By selected molecules in this study, TLRs' potential defectiveness range expands TLRs expression, downstream signaling, and cytokine production. The results show new potential elements that could play a part in TLRs defect and pathogenesis of agammaglobulinemia as well.
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http://dx.doi.org/10.1080/08820139.2019.1604742DOI Listing
November 2019

Resveratrol reduces the expression of insulin-like growth factor-1 and hepatocyte growth factor in stromal cells of women with endometriosis compared with nonendometriotic women.

Phytother Res 2019 Apr 6;33(4):1044-1054. Epub 2019 Mar 6.

Department of Nutrition, School of Public Health, Iran University of Medical Sciences, Tehran, Iran.

Resveratrol, a phytoalexin polyphenol, has antiproliferative, antiangiogenic, anti-inflammatory, and antioxidant properties. The present study has assessed the effect of resveratrol treatment on the expression of insulin-like growth factor-1 (IGF-1) and hepatocyte growth factor (HGF) in endometrial stromal cells (ESCs) from women with and without endometriosis. Endometrial tissues were obtained from 40 endometriotic patients and 15 nonendometriotic control women. After the enzymatic digestion, 13 eutopic ESCs (EuESCs), 8 ectopic ESCs (EESCs), and 11 control ESCs (CESCs) were treated with resveratrol (100 μM) for 6, 24, and 48 hr. The gene and protein expressions of IGF-1 and HGF were measured using real-time polymerase chain reaction and enzyme-linked immunosorbent assay methods, respectively. Results showed that resveratrol treatment decreased significantly the gene expression of IGF-1 and HGF in EuESCs, EESCs, and CESCs (p < 0.05). The effect of resveratrol treatment on the reduction of IGF-1 gene expression was statistically more noticeable in EESCs compared with CESCs (p < 0.05). Also, in the case of HGF gene expression, the reducing effect of resveratrol treatment was statistically more considerable in EESCs compared with EuESCs and CESCs (p < 0.05 and p < 0.01, respectively). The IGF-1 and HGF protein production decreased significantly in EuESCs and EESCs (p < 0.05) but not in CESCs. These findings suggest that resveratrol treatment could reduce the expression of IGF-1 and HGF in ESCs especially in EESCs, which play a pivotal role in disease progression.
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http://dx.doi.org/10.1002/ptr.6298DOI Listing
April 2019

Evaluation of the TLR negative regulatory network in CVID patients.

Genes Immun 2019 03 5;20(3):198-206. Epub 2018 Apr 5.

Immunology Research Center (IRC), Institute of Immunology and Infectious Diseases, Iran University of Medical Sciences, Tehran, Iran.

Common variable immunodeficiency (CVID), a clinically symptomatic primary immunodeficiency disease (PID), is characterized by hypogammaglobulinemia leading to recurrent infections and various complications. Recently, some defects in the signaling of TLRs have been identified in CVID patients which led us to investigate the expression of TLR4 and 9 negative regulatory molecules and their upregulation status following their activation. Using TaqMan real-time PCR, SOCS1, TNFAIP3, RFN216, and IRAK-M transcripts among peripheral blood mononuclear cells (PBMCs) were measured with/without TLR4 and 9 activations. TLR4 and 9 were activated by lipopolysaccharide (LPS) and unmethylated CpG-oligodeoxynucleotide (CpG-ODN), respectively. Production of IFN-α and TNF-α cytokines, as a part of the functional response of mentioned TLRs, was also measured using ELISA. Deficient transcripts of IRAK-M and TNFAIP3 in unstimulated PBMCs and lower production of TNF-α and IFN-α after treatments were observed. Upregulation of RFN216 and TNFAIP3 after TLR9 activation was abnormal compared to healthy individuals. Significant correlations were found between abnormal IRAK-M and TNFAIP3 transcripts, and lymphadenopathy and inflammatory scenarios in patients, respectively. It seems that the transcriptional status of some negative regulatory molecules is disturbed in CVID patients, and this could be caused by the underlying pathogenesis of CVID and could involve complications like autoimmunity and inflammatory responses.
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http://dx.doi.org/10.1038/s41435-018-0022-3DOI Listing
March 2019

1,25-Dihydroxy Vitamin D3 Modulates Endometriosis-Related Features of Human Endometriotic Stromal Cells.

Am J Reprod Immunol 2016 Apr 22;75(4):461-73. Epub 2015 Dec 22.

Immunology Research Center, Iran University of Medical Sciences, Tehran, Iran.

Problem: We aimed to evaluate modulatory effects of vitamin D3 on endometriosis-related features of endometriotic stromal cells.

Method Of Study: The effect of vitamin D3 on adhesion, invasion, proliferation, apoptosis, cytokine production, and angiogenesis potential of the eutopic (EuESCs), ectopic (EESCs), and control (CESCs) stromal cells from 25 women with and 20 women without endometriosis was investigated.

Results: In all groups, vitamin D3 significantly increased cell adhesion (P = 0.0013-0.042), while decreased invasion (P = 0.026-0.031) and proliferation (P = 0.0013-0.039) of EESCs and EuESCs. Such treatment also resulted in a significant decrease in IL-6 production by EESCs (P = 0.039), but had no significant effect on the IL-8 production. This vitamin also caused significant decrease in Bcl-2 gene expression by EuESCs (P = 0.04) and Bcl-xL by EESCs (P = 0.044-0.009). In addition, vitamin D3 treatment reduced VEGF-A gene expression by EESCs (P = 0.046-0.009).

Conclusion: Based on substantial favourable in vitro effects of vitamin D3 in endometriosis-related features of human endometriotic stromal cells, further investigations on therapeutic potential of this hormone in endometriosis are warranted.
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http://dx.doi.org/10.1111/aji.12463DOI Listing
April 2016

Eutopic and ectopic stromal cells from patients with endometriosis exhibit differential invasive, adhesive, and proliferative behavior.

Fertil Steril 2013 Sep 28;100(3):761-9. Epub 2013 May 28.

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

Objective: To study immunophenotype, differential proliferation capacity, invasiveness, adhesion, and cytokine production in ectopic and eutopic endometrial stromal cells (EESCs and EuESCs) from patients with endometriosis.

Design: In vitro study.

Setting: Academic research center.

Patient(s): Patients with ovarian endometriosis (endometrioma) and nonendometriotic controls.

Intervention(s): None.

Main Outcome Measure(s): EESCs and EuESCs from 25 patients with endometrioma and ESCs from 20 nonendometriotic controls (CESCs) were isolated, and their immunophenotype, proliferation, invasion, adhesion, and cytokine production were assessed and compared.

Result(s): Isolated ESCs from all three sources expressed markers specific for cells of mesenchymal origin but were negative for hematopoietic markers. EESCs exhibited a significantly lower proliferation rate in fibronectin-coated plates and less invasive capacity compared with CESCs or EuESCs. Among all stromal cell groups studied, EuESCs showed the highest invasive behavior. EESCs adhered more firmly to extracellular matrix than EuESCs or CESCs in all time intervals examined. The levels of interleukin (IL) -6 and IL-8 production by EESCs were significantly higher compared with those of EuESCs or CESCs.

Conclusion(s): The results of the present study demonstrated that retrograde menstruation alone does not account for the pathogenesis of endometriosis as eutopic and ectopic counterparts of ESCs from patients with endometriosis exhibit differential invasive, adhesive, and proliferative behavior.
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http://dx.doi.org/10.1016/j.fertnstert.2013.04.041DOI Listing
September 2013