Publications by authors named "Ali Gorgin Karaji"

12 Publications

  • Page 1 of 1

Association of interleukin-12B rs6887695 with susceptibility to allergic rhinitis.

Immunol Res 2021 Apr 8;69(2):189-195. Epub 2021 Apr 8.

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

Interleukin-12 (IL-12) is a heterodimeric cytokine encoded by two separate genes, IL12A and IL12B, which may play a regulatory role in allergen-induced inflammation through CD4 T-cell subsets polarization. The aim of this study was to investigate the association of single-nucleotide polymorphisms (SNPs) in the IL12B gene with susceptibility to allergic rhinitis (AR). We performed a case-control study including 130 AR patients and 130 healthy controls to evaluate the possible association between IL12B gene SNPs (rs3212227, rs6887695) and the risk of AR using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Our results showed no significant association between IL12B rs3212227 A > C polymorphism with AR. In contrast, the GC genotype of rs6887695 G > C was associated with susceptibility to AR in comparison with the GG genotype (p = 0.049, OR = 1.684, 95% CI: 1.002-2.83). We also observed a statistically significant difference in the additive model (GC versus GG + CC, p = 0.03, OR = 1.705, 95% CI: 1.040-2.794) for SNPs rs6887695. Furthermore, haplotypes analysis demonstrated that C-C haplotype was associated with an increased risk of AR (p = 0.01, OR = 1.845, 95% CI: 1.114-3.057). Our findings suggest that IL12B rs6887695 polymorphism may be a potential biomarker for susceptibility to AR in an Iranian population.
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http://dx.doi.org/10.1007/s12026-021-09189-1DOI Listing
April 2021

Determination of the transcriptional level of long non-coding RNA NEAT-1, downstream target microRNAs, and genes targeted by microRNAs in diabetic neuropathy patients.

Immunol Lett 2021 Apr 27;232:20-26. Epub 2021 Jan 27.

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

Background: Diabetic neuropathy (DN) is one of the microvascular complications of diabetes that leads to peripheral sensorimotor and autonomic nervous system damages. In this study, we first examined the expression of lncRNA NEAT-1 and its downstream microRNAs, miR-183-5p, miR-433-3p, and then examined mRNA expression of ITGA4, ITGB1, SESN1, and SESN3 as the downstream targets of miR-183-5p, miR-433-3p.

Methods: The blood sample was obtained from a total of 40 patients with type 2 diabetes (20 DN patients and 20 non-DN diabetic cases) and ten healthy individuals. After RNA extraction from peripheral blood samples and cDNA synthesis, expression measurements were performed by the RT-qPCR technique.

Results: Our results showed that the expression level of lncRNA NEAT-1 was significantly higher, and the expression level of miR-183-5p was significantly lower in DN patients compared to the healthy control group. Besides, the expression level of miR-433-3p was significantly lower, and the mRNA expression of ITGA4, SESN1, and SESN3 was significantly higher in DN patients compared to the diabetes group. The ROC curve analysis showed that the miR-183-5p with high levels of accuracy could discriminate DN patients from healthy control (AUC = 0.836) and NEAT-1, SESN1, SESN3, ITGA4 have a high ability to distinguish DN from non-DN patients (AUC = 0.701, 0.772, 0.815 and 0.780, respectively).

Conclusion: It seems that the NEAT-1 probably targets miR-183-5p and miR-433-3p, as a result of which the expression of ITGA4, SESN1, and SESN3 is affected. Dysregulated expression of NEAT-1 and related miRNAs and genes might be involved in the pathogenesis of DN.
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http://dx.doi.org/10.1016/j.imlet.2021.01.007DOI Listing
April 2021

Imbalanced serum levels of resolvin E1 (RvE1) and leukotriene B4 (LTB4) in patients with allergic rhinitis.

Mol Biol Rep 2020 Oct 22;47(10):7745-7754. Epub 2020 Sep 22.

Department of Immunology, School of Medicine, Kermanshah University of Medical Sciences, PO-Box: 6714869914, Kermanshah, Iran.

Timely and successful resolution of acute inflammation plays a crucial role in preventing the development of chronic airway inflammation in allergic rhinitis (AR). This study intends to assess the serum levels of pro-inflammatory leukotriene B4 (LTB4), anti-inflammatory mediators, including resolvin E1 (RvE1), RvD1, IL-10, and TGF-β, besides mRNA expression level of G-protein coupled receptor 120 (GPR120) and peroxisome proliferator-activated receptor-γ (PPAR-γ) receptors in peripheral blood leukocytes of AR patients. Thirty-seven AR patients and thirty age- and gender-matched healthy subjects were enrolled in this study. The serum levels of LTB4, RvE1, RvD1, IL-10, and TGF-β were measured using enzyme-linked immunosorbent assay (ELISA) technique, and the mRNA expression level of GPR120 and PPAR-γ was assessed by the real-time PCR method. The serum levels of RvE1 and LTB4 were significantly higher in patients with AR than in healthy subjects (P < 0.01 and P < 0.0001, respectively). However, a significantly lower ratio of RvE1 and RvD1 to LTB4 was found in patients with AR relative to healthy subjects (P < 0.05 and P < 0.0001, respectively). Likewise, the serum levels of both IL-10 and TGF-β cytokines were significantly reduced in patients with AR compared to healthy subjects (P < 0.01 and P < 0.0001, respectively). Furthermore, the mRNA expression of PPAR-γ was significantly lower in patients with AR than in healthy subjects (P < 0.05). Our findings indicate that imbalanced pro-resolving lipid mediator RvE1 and pro-inflammatory LTB4 might contribute to the defective airway inflammation-resolution and subsequent progression toward chronic inflammation in AR patients.
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http://dx.doi.org/10.1007/s11033-020-05849-xDOI Listing
October 2020

Association between IL-33 Gene Polymorphism (Rs7044343) and Risk of Allergic Rhinitis.

Immunol Invest 2020 Aug 12:1-11. Epub 2020 Aug 12.

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

Background: Allergic rhinitis (AR) is a T helper type 2 (Th2)-mediated upper airways disease in which genetics factors including cytokine genes play a prominent role. Interleukin-33 (IL-33) is a major cytokine for naive T cells polarization into Th2 phenotype as well as enhances the secretion of Th2 cytokines. The aim of the present study was to investigate the relationship between IL-33 single nucleotide polymorphisms (SNPs) and IL-33 serum level with Allergic rhinitis.

Methods: Blood samples were collected from 130 AR patients and 130 healthy individuals. SNPs (rs7044343 C > T, rs1929992 A > G, rs12551256 A > G) of IL-33 gene were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Serum level of IL-33 was measured by enzyme-linked immunosorbent assay (ELISA).

Results: Statistical analysis showed that the TT genotype (OR = 1.996, CI: 1.168-3.412, = .01), as well as the T allele (OR = 0.675, CI: 0.476-0.957, = .02) of rs7044343 C > T were significantly associated with reduced risk of AR. In addition, individuals carrying the TT genotype were associated with lower levels of IL-33 compared to subjects with CC and CT genotypes; however, these differences were not statistically significant. No association was found between rs1929992 and rs12551256 variants and risk of AR, but the GG genotype from rs1929992 A > G was associated with increased serum levels of IL-33 in control group ( = .01). Furthermore, serum IL-33 levels were not significantly different between AR patients and healthy controls ( > .05).

Conclusion: Our results suggest that the TT genotype of rs7044343 C > T may act as a protective agent against allergic rhinitis.
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http://dx.doi.org/10.1080/08820139.2020.1804399DOI Listing
August 2020

Semaphorin 4A, 4C, and 4D: Function comparison in the autoimmunity, allergy, and cancer.

Gene 2020 Jul 31;746:144637. Epub 2020 Mar 31.

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

Semaphorins are a group of proteins that are divided into eight subclasses and identified by a conserved Sema domain on their carboxyl terminus. Sema4A, 4C, and 4D are the members of the fourth class of semaphorin family, which are known as membrane semaphorins; however, these molecules can be altered to soluble semaphorins by proteolytic cleavage. Semaphorins have various roles in the immune, nervous, and metabolic systems. In the immune system, these molecules contribute to the formation of cellular, humoral, and innate immune responses, such as inflammation, leukocyte migration, immunological synapse formation, and germinal center events. Given the diverse roles of semaphorins in the immune system, in this review, we have tried to give a comprehensive look at the role of these molecules in autoimmunity, allergy, and cancer. Sema4D and 4A seem to play a critical role in the pathogenesis of some autoimmune diseases, such as multiple sclerosis. In contrast, it has been shown that Sema4A and 4C have beneficial effects on allergies, and their absence can exacerbate the severity of the disease. In the case of cancer, an increase in all three of these molecules has been reported. Sema4D and 4C can contribute to tumor progression in human patients or experimental models, while the role of Sema4A has not yet been fully understood. In conclusion, semaphorins seem to be a favorable therapeutic target for autoimmune diseases and allergies. However, in cancer, studies have not yet been able to identify the exact role of semaphorins, and further studies are needed.
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http://dx.doi.org/10.1016/j.gene.2020.144637DOI Listing
July 2020

Regulatory T cells for amyotrophic lateral sclerosis/motor neuron disease: A clinical and preclinical systematic review.

J Cell Physiol 2020 06 1;235(6):5030-5040. Epub 2019 Dec 1.

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

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized by neuronal degeneration and inflammation in the nerves. The role of the immune system has been concentrated by researchers in the etiopathogenesis of the disease. Given the inhibitory roles of regulatory T cells (Tregs), it is expected that increasing or activating their populations in patients with ALS can have significant therapeutic effects. Here we searched databases, including CENTRAL, MEDLINE, CINAHL Plus, clinicaltrials.gov, and ICTRP for randomized clinical trials (RCTs) and non-RCTs until March 2019. For preclinical studies, we searched PubMed, Scopus, and Google Scholar up to June 2019. We also included preclinical studies, due to the lack of clinical information available, which used Tregs (or directly targeting them) for treating mice models of ALS. We identified 29 records (CENTRAL 7, MEDLINE 4, CINAHL Plus 8, and clinicaltrials.gov 10) and removed 10 duplicated publications. After screening, we identified one RCT which had been published as an abstract, three non-RCTs, and four ongoing studies. We also identified 551 records (PubMed 446, Google Scholar 68, and Scopus 37) for preclinical studies and performed a meta-analysis. Finally, we found three papers that matched our inclusion criteria for preclinical studies. Results indicated the effectiveness of the application of Tregs in the treatment of ALS. Our meta-analysis on preclinical studies revealed that Tregs significantly prolonged survival in mice models of ALS. Overall, our analysis testified that exertion of Tregs in the treatment of ALS is a promising approach, that notwithstanding, requires further evaluations.
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http://dx.doi.org/10.1002/jcp.29401DOI Listing
June 2020

The role of myeloid-derived suppressor cells in the pathogenesis of rheumatoid arthritis; anti- or pro-inflammatory cells?

Artif Cells Nanomed Biotechnol 2019 Dec;47(1):4149-4158

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

Myeloid-derived suppressor cells (MDSCs) are a heterogeneous group of the immature myeloid cells that are derived from the myeloid progenitors with immunosuppressive functions. MDSCs are accumulated in the inflammatory sites during some autoimmune disorders, such as rheumatoid arthritis (RA) and can be an important factor in the pathogenesis of these diseases. Some research has shown the anti-inflammatory role of MDSCs during the RA progression and supports the hypothesis that MDSCs can be a potential treatment option for autoimmunity with their immunosuppressive activity. In contrast, some papers have reported the opposite effects of MDSCs, and support the hypothesis that MDSCs have a pro-inflammatory role in autoimmune disease. MDSCs functions in RA have not been fully understood, and some controversies, as well as many unanswered questions, remain. Although the two well-known subgroups of MDSCs, M-MDSC, and PMN-MDSC, seem to have different suppressive functions and regulate the immune system responses in a different manner; some studies have shown these cells are converted to each other and even to other cells under different pathological conditions. This review summarises some of the latest papers with respect to the MDSCs functions and discusses the relationship between MDSCs and inflammation in the context of rheumatoid arthritis.
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http://dx.doi.org/10.1080/21691401.2019.1687504DOI Listing
December 2019

In vivo anti-inflammatory efficacy of the combined Bowman-Birk trypsin inhibitor and genistein isoflavone, two biological compounds from soybean.

J Biochem Mol Toxicol 2019 Dec 8;33(12):e22406. Epub 2019 Oct 8.

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

Soybean Bowman-Birk protease inhibitor (BBI) and genistein, two biological compounds from soybean, are well-known for their anti-inflammatory, antioxidant, and anticancer activities. The aim of this study was designing a BBI-genistein conjugate and then investigating its protective effect on lipopolysaccharide (LPS)-induced inflammation in BALB/c mice, compared with the effects of combination of BBI and genistein. BBI was purified from soybean and the BBI-genistein conjugate was synthesized. The BALB/c mice were intraperitoneally treated 2 hours before LPS induction. Our results showed that treatment with the combination of BBI and genistein greatly led to more reduced serum levels of tumor necrosis factor (TNF)-α and interferon (IFN)-γ compared with the treatments of BBI alone, the BBI-genistein conjugate, and genistein alone, respectively. Moreover, the expression of TNF-α and IFN-γ in the splenocytes was significantly downregulated along with improving host survival against the LPS-induced lethal endotoxemia in the same way. Our data support a new combined therapy using BBI and genistein, as natural anti-inflammatory agents, to develop a new drug for inflammatory diseases.
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http://dx.doi.org/10.1002/jbt.22406DOI Listing
December 2019

Immunoresolvents in asthma and allergic diseases: Review and update.

J Cell Physiol 2019 06 29;234(6):8579-8596. Epub 2018 Nov 29.

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

Asthma and allergic diseases are inflammatory conditions developed by excessive reaction of the immune system against normally harmless environmental substances. Although acute inflammation is necessary to eradicate the damaging agents, shifting to chronic inflammation can be potentially detrimental. Essential fatty-acids-derived immunoresolvents, namely, lipoxins, resolvins, protectins, and maresins, are anti-inflammatory compounds that are believed to have protective and beneficial effects in inflammatory disorders, including asthma and allergies. Accordingly, impaired biosynthesis and defective production of immunoresolvents could be involved in the development of chronic inflammation. In this review, recent evidence on the anti-inflam]matory effects of immunoresolvents, their enzymatic biosynthesis routes, as well as their receptors are discussed.
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http://dx.doi.org/10.1002/jcp.27836DOI Listing
June 2019

The opioid antagonist naloxone inhibits Leishmania major infection in BALB/c mice.

Exp Parasitol 2012 Jan 12;130(1):73-7. Epub 2011 Oct 12.

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

BALB/c mice are susceptible to develop non-healing, progressive infection with Leishmania major (L. major) due to the development of a non-protective Th2 response. Resistance to L. major infection is dependent to Th1 response. Treatment of mice with the opioid antagonist naloxone can promote the activation of Th1 responses. Here we study the effect of chronic administration of various doses of naloxone on susceptibility of BALB/c mice to L. major infection. Our results showed that naloxone has dose-dependent biphasic effect on L. major infection in BALB/c mice. While administration of 1mg/kg × 2/day tends to exacerbate the local reaction to L. major infection, treatment with 10mg/kg × 2/day of naloxone suppresses the local reaction and progress of infection. On the other hand treatment of mice with middle dose (5mg/kg whether 1 or 2 times per day) does not have significant effect on the infection. This study demonstrates that administration of high dose of naloxone could improve protection against L. major infection in BALB/c mice, presumably by modulation in Th1/Th2 balance or by affecting macrophages through binding to Toll-like receptors.
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http://dx.doi.org/10.1016/j.exppara.2011.09.006DOI Listing
January 2012

Application of popliteal lymph node assay to evaluate tolerogenic effect of donor leukocyte infusion.

Transpl Immunol 2006 Jun 19;16(1):20-4. Epub 2006 Apr 19.

Department of Microbiology and Immunology, School of Medicine, Kermanshah University of Medical Sciences, Iran.

Background: Popliteal lymph node assay (PLNA) has long been proposed to detect immunostimulating potential of chemicals. Here, the PLNA was used to evaluate the effect of donor leukocyte infusion on recipients' reaction to donor-specific antigens.

Methods: Donor rats' peripheral blood leukocytes (ranging from 1 x 10(4) to 500 x 10(4) cells) were intravenously (i.v.) infused into recipients. A week later recipients' reaction to donor-specific antigen was evaluated, using the PLNA technique, by subcutaneous injection of donor spleen cells to one hind footpad of recipients and injection of saline to the other. Seven days later all recipients were killed and their PLNs' weight and cellularity indices were determined. While the same process was applied to the positive control (PC) animals, rats without leukocyte infusion, negative control (NC) animals, rats without leukocyte infusion, were injected in both hind footpads with saline.

Results: The PLN weight indices of recipients of: > or =5 x 10(4) leukocytes were significantly lower than PC animals (P < 0.001), whereas the weight indices of recipients of 1 x 10(4) cells were similar to PC group but higher than NC animals (P < 0.0001). However, the PLN cellularity indices of recipients of < or =10 x 10(4) cells were not different from PC animals but the PLN cellularity indices of recipients of: > or =50 x 10(4) cells were significantly lower than PC group (P < 0.05).

Conclusion: Overall, these results suggest that donor leukocytes infusion dose-dependently decrease reaction to donor-specific antigens, but a state of tolerance to donor antigen might be induced at the dose of: > or =50 x 10(4) cells. PLNA appears to represent a simple test model to quantify efficacy of immunotolerance protocols.
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http://dx.doi.org/10.1016/j.trim.2006.03.005DOI Listing
June 2006

Detection of opioid receptors on murine lymphocytes by indirect immunofluorescence: mature normal and tumor bearing mice lymphocytes.

Int Immunopharmacol 2005 Jun;5(6):1019-27

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

Opioid peptides modulate immune responses via ligation to classical opioid receptors (mu, delta and kappa), expressed on immune cells, or in an indirect fashion via the central nervous system. The combination of immunofluorescent technique and flow cytometry has proven to be sensitive methods for detection of opioid receptors on leukocytes. In the current study a fluorescein isothiocyanate-conjugated naltrexone (FITC-NTX) derivative in the absence or presence of naltrexone, as a competitor, was used to detect opioid receptors on thymocytes and then on splenocytes of normal and tumor bearing Balb/c mice. Tumor bearing mice were made by intraperitoneal injection of fibrosarcoma cell line. In a two weeks interval, tumor grew and then mice splenocytes were harvested. Cells were incubated with FITC-NTX alone (direct fluorescence), or FITC-NTX followed by biotin-conjugated anti-fluorescein IgG and extravidin-R-phycoerythrin (indirect immunofluorescence). Using flow cytometry we found that, with direct fluorescence staining there is only nonspecific cell staining. In contrast, indirect staining of cells demonstrated labeling of opioid receptors. Thymocytes displayed 37.5+/-7% specific labeling by current staining procedure. However, this specific staining was 17.2+/-4% and 7.5+/-2% in splenocytes of normal and tumor bearing mice, respectively. Taken together, these results showed that, direct fluorescence staining failed to stain opioid receptors expressed on lymphocytes. These receptors can only be detected by a biotin-streptavidin amplification procedure. We also found that the level of opioid receptors on mature lymphocytes is less than that of immature ones and are even lesser in the tumor bearing mice lymphocytes.
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http://dx.doi.org/10.1016/j.intimp.2005.01.012DOI Listing
June 2005