Shiraz Institute for Cancer ResearchIranian Journal of Immunology1735-13832220050601The Jak-Stat Signaling Pathway of Interferons System: Snapshots677716843ENMasoumehVarediDepartment of Physiology, Medical School, Shiraz University of Medical Sciences, Shiraz, IranJournal Article20160805Interferons (IFNs) are a family of small regulatory glycoproteins that play a central role in the defense against viral infections. Although IFNs have been initially discovered as antiviral factors, today they are known as an integral part of the cytokine network that affect a wide range of biological processes. IFNs exert their pleiotropic effects through their multisubunit cell surface receptors in a species specific manner that is believed to be controlled at the receptor and the post-receptor levels. Although IFN-mediated signaling and transcription activation of cellular gene expression is currently best understood in the context of the JAK-STAT signal transduction, additional IFNs signaling pathways may also act in certain conditions. The <em><span><span>Janus </span></span></em><span style="font-family: TimesNewRomanPSMT; font-size: medium;"><span style="font-family: TimesNewRomanPSMT; font-size: medium;">family of</span></span> tyrosine kinase (JAK) enzymes and two families of transcriptional regulators, signal transducer and activator of transcription (STATS) and IFN regulatory factors (IRFs), are the principal components of the JAK-STAT pathway. Overlapping subsets of JAKS are involved in signaling by type I (IFN- <span style="font-family: SymbolMT; font-size: medium;"><span style="font-family: SymbolMT; font-size: medium;">α</span></span><span style="font-family: TimesNewRomanPSMT; font-size: medium;"><span style="font-family: TimesNewRomanPSMT; font-size: medium;">/ß) and type II (IFN-</span></span><span style="font-family: SymbolMT; font-size: medium;"><span style="font-family: SymbolMT; font-size: medium;">γ</span></span><span style="font-family: TimesNewRomanPSMT; font-size: medium;" lang="ZH-TW"><span style="font-family: TimesNewRomanPSMT; font-size: medium;" lang="ZH-TW"> </span></span><span style="font-family: TimesNewRomanPSMT; font-size: medium;"><span style="font-family: TimesNewRomanPSMT; font-size: medium;">IFNs, indicating that the receptor subunits confer specificity</span></span> for activating particular JAK family members. A considerable cross talk can exist between separate signaling pathways. The emergence of new tools and approaches for study of IFNs signaling has been an exercise in coming to respect the level of complexity of IFNs system. For many years, IFNs have been satisfactorily used in many clinical trials. However, their serious side effects remain as the major concern in clinical use of IFNs. A better understanding of the exact mechanism involved in IFNs signaling pathways and the structure-function relationships of the IFNs system components will allow researchers to improve and expand the therapeutic potential of these naturally occurring molecules. IFNs actions are mediated through multiple signaling pathways. However, due to the space limitation, this review will focus primarily on the IFNs-mediated JAK-STAT pathway.https://iji.sums.ac.ir/article_16843_4debdb1b039881ad3a7ebf757157d7be.pdfShiraz Institute for Cancer ResearchIranian Journal of Immunology1735-13832220050601Differential Immunohistochemical Expression Pattern of Galectin-3 in Normal and Osteoarthritic Human Articular Cartilage788616844ENMahmoudOrazizadehDepartment of Histology, Medical School, Ahwaz Jondishapour University of Medical Sciences (AJUMS), Ahwaz,
IranDonald MSalterDepartment of Pathology, Medical School, Edinburgh University, Edinburgh, Scotland, UKJournal Article20160805<b>Background</b>: <span><span>Previous studies have shown that Galectin-3, a member of lectin family, is expressed</span></span> in developing cartilage in mouse embryo and also in growth plate of long bones. <span><span><br/><b>Objective</b>: </span></span><span><span>In the</span></span> present work, the expression pattern of Galectin-3 in normal and various grades of osteoarthritic (OA) human articular cartilage has been studied. <span><span><br/><b>Methods</b>: </span></span><span><span>Using immunohistochemistry and</span></span> standard western blotting, the in vivo and in vitro expression pattern of Galectin-3 in normal and OA human articular cartilage were assessed. <span><span><br/><b>Results</b>: </span></span><span><span>Immunohistochemical studies showed a</span></span> similar pattern of Galectin-3 expression in normal and mild OA but severe OA showed different strong expression in all zones of human articular cartilage. <span><span><br/><b>Conclusion</b>: </span></span><span><span>Increased expression</span></span> pattern of Galectin-3 in advanced stages of OA may occur as a result of the imbalance of chondrocyte homeostasis that occurs in OA cartilage and provides a condition to modify normal chondrocyte to an OA chondroctye.https://iji.sums.ac.ir/article_16844_a124cc9fab8cc57f5811a5034d80d8fd.pdfShiraz Institute for Cancer ResearchIranian Journal of Immunology1735-13832220050601Prediction of Rejection in Renal Transplantation by Immune Parameters879016845ENMahboobLessan-PezeshkiDepartment of Immunology, Tehran University of Medical Sciences, Tehran, IranAli AkbarAmirzargarDepartment of Immunology, Tehran University of Medical Sciences, Tehran, Iran0000-0002-7442-2519NooshinGolabiDepartment of Immunology, Tehran University of Medical Sciences, Tehran, IranMohammadrezaKhatamiDepartment of Immunology, Tehran University of Medical Sciences, Tehran, IranBehzadEinollahiDepartment of Immunology, Tehran University of Medical Sciences, Tehran, IranVahidPourfarzianiDepartment of Immunology, Tehran University of Medical Sciences, Tehran, IranFaridehKhosraviDepartment of Immunology, Tehran University of Medical Sciences, Tehran, IranHassanehTajerzadehDepartment of Immunology, Tehran University of Medical Sciences, Tehran, IranBehrouzNikbinDepartment of Immunology, Tehran University of Medical Sciences, Tehran, IranJournal Article20160805<b>Background</b>: <span><span>Monitoring of phenotypic characteristics of T-lymphocytes in peripheral blood is</span></span> commonly performed to give the clinical parameters in the management of kidney transplant recipients. <span><span><br/><b>Objective</b>: </span></span><span><span>To predict rejection in renal transplantation by immune parameters.</span></span> <br/><b>Methods</b>: <span><span>16 non-diabetic kidney transplant candidates (4 females and 12 males, age = 20-65 yr,</span></span> first time transplant) were selected. The transplanted patients were divided into two groups based on the rejection during 3 weeks post transplant: group I (n = 9) without rejection and group II (n = 7) with a rejection episode. Immune parameters including lymphocytes subpopulations (by flowcytometry) and immunoglobulin classes (IgM, IgG, IgA and IgE by nephlometric assay) before and 45 days after transplantation were determined. <span><span><br/><b>Results</b>: </span></span><span><span>The results of this investigation</span></span> showed that the level of immunoglobulin IgG, IgM, IgA and IgE decreased post transplantation due to immunosuppressive drugs. CD3, CD4, CD8 T cells count, CD56 NK cells count and CD20 B cells count pre- and post-transplantation did not show any significant differences. The amount of IgE (220 <em><span><span>vs. </span></span></em><span><span>462 IU/ml), CD3 (62% </span></span><em><span><span>vs. </span></span></em><span><span>69.7%) and CD4 (35% </span></span><em><span><span>vs. </span></span></em><span><span>41.3%) cells increased in</span></span> group II during rejection episode pre-transplantation. In addition, IgA increased pretransplantation in group I those without rejection episode in comparison with group II with a rejection episode. Forty five days post transplantation IgA (209 <em><span><span>vs. </span></span></em><span><span>152 mg/dl), IgG (1009 </span></span><em><span><span>vs. </span></span></em><span><span>703</span></span> mg/dl) and CD20 (15% <em><span><span>vs. </span></span></em><span><span>10%) increased in group I patients. </span></span><span><span><br/><b>Conclusion</b>: </span></span><span><span>It is suggestive that</span></span> pre-transplantation increases IgE, CD3 and CD4 are predictive of acute rejection.https://iji.sums.ac.ir/article_16845_c4188a4cab6b8f89e0fa26ad57ef33ab.pdfShiraz Institute for Cancer ResearchIranian Journal of Immunology1735-13832220050601A Flowcytometry Study of CD55 and CD59 Expression on Erythrocytes in Rheumatoid Arthritis Patients919616846ENAbbas AliPourazarImmunology DepartmentAlirezaAndalibImmunology Department0000-0002-2032-6281FarzadQreizyImmunology DepartmentHadiKarimzadehInternal Medicine Department, Isfahan Medical School, Isfahan University of Medical
Sciences, Isfahan, IranAhmadGhavami-NejadImmunology DepartmentBehshadPournasr-KhakbazImmunology DepartmentJournal Article20160805<b>Background</b>: <span><span>Inappropriate activation or blockage of the inhibition of complement system could</span></span> cause tissue damages in autoimmune diseases particularly rheumatoid arthritis (RA). Defect in complement component regulation may cause damages to tissues, on the other hand, or the damaged tissue might affect the unnecessary activation of complement components. <span><span><br/><b>Objective</b>: </span></span><span><span>To</span></span> investigate the expression of CD55 and CD 59 complement regulatory proteins in RA patients. Subjects and <br/><b>Methods</b>: <span><span>Fifty proved rheumatoid arthritis patients participated in this study and</span></span> their blood were collected for investigations. CD55 and CD59 molecules expression on the erythrocytes was assayed using primary monoclonal antibody and secondary FITC conjugated Ab, then the prepared samples were run with a FACSCalibur flowcytometer (Becton-Dickinson) and the obtained data was analyzed using a Cell Quest software package. To evaluate the complement function, CH50 was performed using patient sera. All experiments were done with a matched healthy volunteer group. <span><span>Results</span></span><span><span>: The mean fluorescence intensity for CD55 was 27.6</span></span> ± 13.4 arbitrary unit for patients and 68.5 ± 10.5 for healthy group. CD59 mean fluorescence intensity was 314 ± 83 in patient group and 508 ± 56 in healthy volunteers. In addition, there was a significant difference between CH50 in patients (54.5 ± 15.5) and in healthy group (110 ± 20). A significant correlation between CD55 and CD59 expansion on the patient erythrocytes was found (P = 0.00, r = 0.576). No association was found between CD59, or CD55 with CH50 (P > 0.05). <span><span><br/><b>Conclusion</b>: </span></span><span><span>The expression of CD55 and CD59 is down-regulated on erythrocytes</span></span> of patients with RA. Change in expression of regulatory complement components in RA may be a useful key for the assessment of disease progression or in patients' follow-up.https://iji.sums.ac.ir/article_16846_0f2118efe1ad586e1c19dbadb949b76d.pdfShiraz Institute for Cancer ResearchIranian Journal of Immunology1735-13832220050601Lack of Association between ctla-4 A49G Polymorphism and Vitiligo9710216847ENMohammad JavadFattahiDepartment of ImmunologyAbdul MohammadPezeshkiShiraz Institute for Cancer ResearchMaryamEmadDepartment of Dermatology, Shiraz University
of Medical Sciences, Shiraz, IranMohammad HoseinLohrasbDepartment of Immunology andAzraShamseddinDermatology, Fasa Medical School, Fasa, IranAbbasGhaderiDepartment of ImmunologyShiraz Institute for Cancer Research0000-0003-0849-3375MehrnooshDoroudchiDepartment of ImmunologyShiraz Institute for Cancer Research0000-0003-4067-5400Journal Article20160805<span><b>Background</b>: </span> <span style="font-family: TimesNewRomanPSMT; font-size: medium;"><span style="font-family: TimesNewRomanPSMT; font-size: medium;"><span>Vitiligo is an acquired skin disorder that selectively destroys melanocytes in</span></span></span> epidermis with an unknown etiology. <span><span><br/><b>Objective</b>: </span></span><span style="font-family: TimesNewRomanPSMT; font-size: medium;"><span style="font-family: TimesNewRomanPSMT; font-size: medium;">To investigate the exon 1 A49G polymorphism</span></span> of cytotoxic T lymphocyte antigen-4 (ctla-4) gene in vitiligo patients. <span><span><br/><b>Methods</b>: </span></span><span style="font-family: TimesNewRomanPSMT; font-size: medium;"><span style="font-family: TimesNewRomanPSMT; font-size: medium;">The</span></span> A49G polymorphism was detected by Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) method in 101 patients and 208 normal healthy age/ethnicity matched individuals. <span><span><br/><b>Results</b>: </span></span><span style="font-family: TimesNewRomanPSMT; font-size: medium;"><span style="font-family: TimesNewRomanPSMT; font-size: medium;">The frequencies of heterozygote genotypes in</span></span> patients and controls were found to be 42 (41.6%) of 101 and 85 (40.9%) of 208, respectively. The frequencies of homozygote A and G genotypes were 49 (48.5%) and 10 (9.9%) in 101 patients, whereas, these frequencies in 208 control individuals were 103 (49.5%) and 20 (9.6%), respectively. There was no significant difference between the genotype (P = 0.98) and allele (P = 0.86) frequencies of A49G polymorphism in patients and normal healthy individuals. <span><span><br/><b>Conclusion</b>: </span></span><span style="font-family: TimesNewRomanPSMT; font-size: medium;"><span style="font-family: TimesNewRomanPSMT; font-size: medium;">Our results indicate that in contrast to several immune mediated</span></span> disorders, there is no association between ctla-4 A49G gene polymorphism and vitiligo.https://iji.sums.ac.ir/article_16847_dc8e8917d4a865f01b88f08c1a3672e1.pdfShiraz Institute for Cancer ResearchIranian Journal of Immunology1735-13832220050601Level of Nitric Oxide in Bronchoalveolar Lavage Fluid of Asthmatic Mice Model10311016848ENAlirezaSalek MoghaddamDepartment of Immunology0000-0000-0000-0000MohammadShabaniDepartment of Biochemistry, Iran University of Medical Sciences, Tehran, IranFarahdokhtFateminasabDepartment of ImmunologyMohammad RezaKhakzadDepartment of ImmunologyJournal Article20160805<span><b>Background</b>: </span> <span><span><span>Asthma is a chronic inflammatory disease with multifactorial and complicated</span></span></span> <span>mechanisms. Elevated level of exhaled Nitric Oxide (NO) in asthma and other inflammatory</span> <span>lung diseases has led to many studies examining NO as a potential marker of airway inflammation.</span> <span><br/><b>Objective</b>: </span> <span><span><span>This study was designed to determine the level of NO in Bronchoalveolar Lavage</span></span></span> <span>(BAL) fluid during early and late stages of asthmatic attack in mouse model. </span> <span><span><span><br/><b>Methods</b>: </span></span></span><span><span><span>In</span></span></span> <span>this study male BALB/c mice were used. The level of NO was determined in BAL fluid of</span> <span>asthmatic mice five minutes, six and sixteen hours after challenge with methacholine, as irritant</span> <span>and smoke and 5% ovalbumin as allergens, using colorimetric assay. </span> <span><span><span><br/><b>Results</b>: </span></span></span><span><span><span>The level of NO</span></span></span> <span>increased upon exposure to all three irritants used in this study (52.3 </span> <span><span lang="JA"><span lang="JA">μ</span></span><span><span>M for smoke and 49.5</span></span></span> μ <span><span>Mfor methacholine) as compared to 22.8 </span></span><span style="font-family: SymbolMT; font-size: medium;" lang="JA"><span style="font-family: SymbolMT; font-size: medium;" lang="JA">μ</span></span><span><span>M for the baseline. Our results showed that NO levels</span></span> were increased during early phase of asthmatic condition and reached to its maximum level after six hours and decreased at the late stage of asthma (16hrs) possibly by activating a feedback regulatory loop. In addition, high level of NO led to the hypertrophy of smooth muscle that can account for the pathological changes associated with asthma. <span><span><br/><b>Conclusion</b>: </span></span><span><span>Thus, NO is an</span></span> inflammatory marker in asthma and its measurement, as a non-invasive method during asthmatic attack is suggested. A careful development of specific inhibitors for iNOS enzyme during asthmatic attack is also necessary.https://iji.sums.ac.ir/article_16848_94c229943dbf8bf0390d2987226c4fe7.pdfShiraz Institute for Cancer ResearchIranian Journal of Immunology1735-13832220050601Increased Natural Killer Cells Activity in Schizophrenic Patients11111616849ENMohammadVodjganiDepartment of Immunology, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, IranHediehMatloubiDepartment of Immunology, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, IranAbbas AliNasehiDepartment of Immunology, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, IranMohammad HosseinNiknamDepartment of Immunology, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, IranAnoushirvanKazemnejadDepartment of Immunology, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, IranEisaSalehiDepartment of Immunology, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, IranTaherehAboufazeliDepartment of Immunology, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, IranZahraGheflatiDepartment of Immunology, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, IranJournal Article20160805<b>Background</b>: <span><span>Schizophrenia has been associated with altered immunity. Different studies regarding</span></span> natural killer cell activity (NKA) in schizophrenic patients have shown inconsistent results. <br/><b>Objectives</b>: <span><span>To evaluate NK cell activity in schizophrenic patients in comparison with</span></span> healthy control individuals. <span><span><br/><b>Methods</b>: </span></span><span><span>30 medication-free schizophrenic patients and 41 healthy</span></span> sex, age and smoking status matched individuals were included in this study. NK cell activity of case and control subjects was measured by Methyl-Thiazol-Tetrazolium (MTT) test. Statistical analysis of the data was done using SPSS 11.5 software. <span><span>Results</span></span><span><span>: NK activity of patients and</span></span> normal subjects had a mean of 36.94 ± 26.15 (Mean ± SD) and 22.31 ± 17.92, respectively. A significant increase in NK activity in schizophrenic patients compared to controls (P = 0.011). Among patients, NK activity of smokers was significantly lower than that of non-smokers (P = 0.02). Other demographic factors didn't show any influence on NK activity. <span><span><br/><b>Conclusion</b>: </span></span><span><span>The</span></span> higher activity of NK cells in the schizophrenic patients as compared with the control population could explain the low incidence of cancer in these patients. Decreasing the effect of smoking on NK activity in the patients could be one of the responsible factors for the inconsistency in the results of different studies.https://iji.sums.ac.ir/article_16849_2a058254f582a29eb1d582b819ca9332.pdfShiraz Institute for Cancer ResearchIranian Journal of Immunology1735-13832220050601Flowcytometric Analysis of Tumor Associated Macrophages in Invasive Ductal Carcinoma of Breast11712216850ENDawarAmaniDepartment of Immunology, Medical School, Ardabil University of Medical Sciences, Ardabi, Iran0000-0001-7277-4484Zohair MohammadHassanDepartment of
Immunology, Medical School, Tarbiat Modarres University, Tehran, IranFatemehRavangardDepartment of Immunology, Medical School, Ardabil University of Medical Sciences, Ardabi, IranSusanFrazmandDepartment of
Immunology, Medical School, Tarbiat Modarres University, Tehran, IranMojtabaKarim ZadehDepartment of
Immunology, Medical School, Tarbiat Modarres University, Tehran, IranJournal Article20160805<b>Background</b>: <span><span>Invasive ductal carcinoma is the most common type of breast cancer in Iran. Impaired</span></span> immune responses occur frequently in cancer patients, but the mechanisms of the induced immune defects remain poorly understood. It is believed that infiltrated immune cells, especially macrophages, may provide help for tumor cell growth and metastasis. <span><span><br/><b>Objective</b>: </span></span><span><span>To analyze the</span></span> status of tumor associated macrophages (TAM) by immunophenotyping method. <span><span><br/><b>Methods</b>:</span></span> Twenty-three women suffering from breast cancer were examined; nineteen of them were confirmed histologically to have invasive ductal carcinoma. Tumor cell suspensions from biopsy specimens and peripheral blood mononuclear cells from patients and matched controls were processed for analysis by flow cytometry. <span><span><br/><b>Results</b>: </span></span><span><span>No significant changes in the percentages of</span></span> intra-tumor leukocytes and macrophages in the different stages of tumor were observed. There were no significant differences in the percentages of leukocytes (CD45 <span style="font-family: Times New Roman; font-size: xx-small;"><span style="font-family: Times New Roman; font-size: xx-small;">+</span></span><span><span>), monocytes</span></span> (CD45 <span style="font-family: Times New Roman; font-size: xx-small;"><span style="font-family: Times New Roman; font-size: xx-small;">+</span></span><span><span>/CD14</span></span><span style="font-family: Times New Roman; font-size: xx-small;"><span style="font-family: Times New Roman; font-size: xx-small;">+</span></span><span><span>) and activated monocytes (CD14</span></span><span style="font-family: Times New Roman; font-size: xx-small;"><span style="font-family: Times New Roman; font-size: xx-small;">+</span></span><span><span>/HLA-DR</span></span><span style="font-family: Times New Roman; font-size: xx-small;"><span style="font-family: Times New Roman; font-size: xx-small;">+ </span></span><span><span>and CD14</span></span><span style="font-family: Times New Roman; font-size: xx-small;"><span style="font-family: Times New Roman; font-size: xx-small;">+</span></span><span><span>/CD16</span></span><span style="font-family: Times New Roman; font-size: xx-small;"><span style="font-family: Times New Roman; font-size: xx-small;">+</span></span><span><span>) in the peripheral</span></span> blood of patients and controls. <span><span><br/><b>Conclusion</b>: </span></span><span><span>The results of this study indicated that human</span></span> breast cancer contain substantial, although variable numbers of macrophages, however, the activation status of these macrophages remain to be elucidated.https://iji.sums.ac.ir/article_16850_7be35d39d2ccccbab29b3d302af06bc0.pdf