Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 18 1 2019 02 24 1 11 EN Saloomeh Fouladi Department of Immunology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran Mohsen Masjedi Department of Immunology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran Mazdak Ganjalikhani Hakemi Department of Immunology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran Nahid Eskandari Department of Immunology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran 2017 11 22 2018 05 16 Allergic asthma is the most common type of allergy which have become increasingly prevalent in all around the world. Airway eosinophilic inflammation is a major feature of allergic asthma. Glycyrrhiza uralensis (licorice) is one of the regular herbs in traditional Chinese medicine (TCM) as it has many effects on the immune system such as anti-inflammatory and immune regulatory activity; antiviral and antitumor effects. This review focuses on the "licorice” components, mainly glycyrrhizic acid (GA) and derivatives structure that evaluate its effects on the allergic asthma. We performed searching articles in Pubmed, Web of Science, and Scopus data bank from 1990 to 2017. The search syntax were: "glycyrrhizin" OR " glycyrrhizic acid" OR " glycyrrhizinic acid" OR" glycyrrhiza glabra" OR " liquorice root" OR "G. glabra" OR "glycyrrhizic Acid" AND "allergic asthma" OR "bronchial asthma" OR "asthma, bronchial" OR "airway hyper-responsiveness" OR "airway inflammation". Several molecular mechanisms and inflammatory mediators may possibly be responsible for efficacy of glycyrrhizin. Some in vitro studies indicated to the fact that possible mechanisms of anti-inflammatory effects could be through reduction of pro-inflammatory mediator's synthesis that motivates eosinophil, basophils and mast cells to release cytokines for the differentiation of T helper cells into Th2 cells to secrete interleukins. Furthermore, some transcription factors such as NF-κB, STAT6 and HDAC2 go between modulations of anti-asthmatic effects. The last but not the least it can be said that glycyrrhizin is potentially a good herbal drug with the lower most adverse effects for asthma treatment. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/1740 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/1740/1398

Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 18 1 2019 02 24 12 26 EN Farzaneh Shakeri Natural Products and Medicinal Plants Research Center, North Khorasan University of Medical Sciences, Bojnurd, Iran Vahideh Ghorani Department of Physiology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran AND Neurogenic Inflammation Research Center, Mashhad University of Medical Sciences, Mashhad, Iran Saeideh Saadat Department of Physiology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran AND Neurogenic Inflammation Research Center, Mashhad University of Medical Sciences, Mashhad, Iran Zahra Gholamnezhad Department of Physiology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran AND Neurogenic Inflammation Research Center, Mashhad University of Medical Sciences, Mashhad, Iran Mohammad Hossein Boskabady Department of Physiology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran AND Neurogenic Inflammation Research Center, Mashhad University of Medical Sciences, Mashhad, Iran 2017 12 28 2018 05 09 Medicinal plants have been identified and used as primary sources in prevention and treatment of pulmonary diseases (mainly obstructive pulmonary diseases) from ancient times due to various pharmacological activities. In this review, the stimulatory effects of extracts, some fractions and constituents of medicinal plants on β2-adrenoceptors which could be used as possible therapeutic agents in the future were reviewed. Various databases including; Medline, PubMed, ScienceDirect, Scopus, and Google Scholar were searched using stimulatory effect, β2-adrenoceptors, possible mechanism, tracheal smooth muscle (TSM), medicinal plants and their constituents as keywords from 1985 to 2017. All studied plants including; Nigella sativa, Rosa damascena, Thymus vulgaris, Carum copticom, Carum carvi, Zataria multiflora, Crocus sativus, Cuminum cyminum, Liomnia acidissima, Portulaca oleraceae, Satureja hortensis, Ephedra sinica and Achillea millefolium showed relaxant effect on tracheal smooth muscle with a stimulatory effect on β2-adrenoceptors mechanism. The studied plants and their constituents could be of therapeutic value in clinical practice as a bronchodilatory drug by β2-adrenoceptors stimulatory mechanism for treatment of obstructive pulmonary diseases. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/1803 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/1803/1378

Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 18 1 2019 02 02 27 37 EN Emel Ceylan Department of Pulmonary Medicine, Adnan Menderes University Medical School, Aydın, Turkey Sertan Bulut Department of Pulmonary Medicine, Atatürk Chest Diseases and Chest Surgery Education and Research Hospital, Ankara, Turkey Mustafa Yilmaz Department of Biochemistry, Adnan Menderes University Medical School, Aydın, Turkey Hüseyin Örün Department of Pulmonary Medicine, Adnan Menderes University Medical School, Aydın, Turkey Fisun Karadağ Department of Pulmonary Medicine, Adnan Menderes University Medical School, Aydın, Turkey İmran Ömürlü Department of Biostatistics, Adnan Menderes University Medical School, Aydın, Turkey Sevin Kirdar Department of Clinical Microbiology, Adnan Menderes University Medical School, Aydın, Turkey Aslıhan Karul Department of Biochemistry, Adnan Menderes University Medical School, Aydın, Turkey 2017 11 25 2018 05 09 The effects of comorbidities on systemic inflammation markers in stable asthmatics and the consequences of such effects have not been well evaluated. We aimed to evaluate the effect of comorbidities on clinical manifestations and systemic inflammation in asthmatic patients under control. The study group consisted of asthmatic patients who applied to our pulmonology outpatient clinic and volunteered to participate. 120 clinically stable asthma patients (71 females and 49 males) and 35 healthy controls (19 females and 16 males) with similar age, gender, and body mass index distributions were admitted to the study. The levels of osteopontin, interleukin 6 (IL-6), interleukin 8 (IL-8), interleukin 13 (IL-13), eosinophilic cationic protein, adiponectin, and high-sensitivity C-reactive protein of the individuals were evaluated using commercial ELISA kits by taking venous blood samples. Of 120 asthmatic subjects, 47 (39, 2%) had comorbidities and allergic rhinitis (15%) coexisted most frequently. Other comorbidities associated with asthma were gastroesophageal reflux, sinusitis, hypertension, diabetes, gastritis, and peptic ulcus respectively. There was no physician-diagnosed comorbidity in the control group. The levels of IL-6 and IL-8 were found higher in asthma group with comorbidities when compared to those with no comorbidities (p were 0.032 and 0.046, respectively). Comorbidities interfere with the diagnosis and treatment of asthma, besides affecting the disease control. Our findings suggest the possibility of the impact of comorbidities on systemic inflammation markers, especially IL-6 and IL-8. To evaluate the impact of comorbidities on asthma control and systemic markers, further studies are needed. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/1750 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/1750/1390

Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 18 1 2019 02 24 38 47 EN Shole Faridi Department of Microbiology, Faculty of Veterinary Medicine, Urmia University, Urmia, Iran Norouz Delirezh Department of Microbiology, Faculty of Veterinary Medicine, Urmia University, Urmia, Iran Seyyed Meysam Abtahi Froushani Department of Microbiology, Faculty of Veterinary Medicine, Urmia University, Urmia, Iran 2018 03 02 2018 07 30 Streptozocin (STZ) is a strong alkalizing agent which is capable of destroying the beta cells of the pancreatic islets. Multiple low doses (40 mg/kg, intraperitoneally for 5 consecutive days) prescription of STZ to mice can lead to the T cell-dependent immune response and induction of autoimmune diabetes (AD) with complete similarity to the human type 1 diabetes (T1D). This study has evaluated the effects of hydroalcoholic extract of saffron on the clinical and immunological profile of experimental autoimmune diabetes in C57BL/6 mice. After the establishment of the AD, mice were treated orally with hydroalcoholic extract of saffron (500 mg/kg) for 3 weeks. The results with p<0.05 were considered significant. Obtained data showed that treatment with the hydroalcoholic extract of saffron significantly reduced the incidence of hypoglycemia and restored insulin secretion and histopathological changes in pancreas sections. In addition, treatment with saffron reduced lymphocyte proliferation index in the cells isolated from the pancreas of diabetic mice. Also, the extract of saffron markedly decreased the production of pro-inflammatory interleukin-17 (IL-17) increased anti-inflammatory IL-10 and transforming growth factor-β in the pancreatic cell population. Moreover, the production of proinflammatory nitric oxide and reactive oxygen substances were down-regulated by the saffron extract. It seems that the hydroalcoholic extract of saffron can be considered as a useful strategy in the treatment of type 1 diabetes. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/1886 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/1886/1389

Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 18 1 2019 02 24 48 61 EN Hassan Ghobadi Department of Internal Medicine, Pulmonary Division, School of Medicine, Ardabil University of Medical Sciences, Ardabil, Iran Mohammad Reza Alipour Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran Rana Keyhanmanesh Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran Mohammad Hossein Boskabady Neurogenetic Inflammation Research Center, Mashhad University of Medical Sciences, Mashhad, Iran Mohammad Reza Aslani Ardabil Imam Khomeini Educational and Clinical Hospital, Ardabil University of Medical Sciences, Ardabil, Iran 2018 02 15 2018 07 18 Epidemiological and clinical studies have demonstrated a close association between obesity and asthma. The current study investigated the effect of high-fat diet on tracheal responsiveness to methacholine and insulin resistance in ovalbumin (OVA) sensitized male and female rats. The rats were divided into eight groups (n=6 per group): female with the normal diet (F+ND), male with the normal diet (M+ND), female OVA-sensitized with the normal diet (F+SND), male OVA-sensitized with the normal diet (M+SND), female with high-fat diet (F+HFD), male with high-fat diet (M+HFD), female OVA-sensitized with high-fat diet (F+SHFD), and male OVA-sensitized with high-fat diet (M+SHFD). All rats were fed for 8 weeks with high-fat diet or standard pelts, and for another 4 weeks, they were sensitized with OVA or saline. At the end of the study, the tracheal responsiveness to methacholine, serum insulin, and blood glucose levels was measured. Also, insulin resistance indexes were determined. OVA-sensitization and diet-induced obesity caused the curve of methacholine concentration response to shifting to the left. In addition, results indicated that the EC50 (the effective concentration of methacholine generating 50% of peak response) in F+SHFD rats was statistically lower than M+SHFD group (p<0.05). Moreover, insulin resistance was higher in the F+SHFD than the M+SHFD group (p<0.001). These results suggest that insulin resistance and metabolic syndrome may be involved in the pathogenesis of obesity associated with OVA-sensitized rats condition, especially in female animals.   https://ijaai.tums.ac.ir/index.php/ijaai/article/view/1874 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/1874/1394

Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 18 1 2019 02 24 62 71 EN Lei Chong Institute of Pediatrics, National Key Clinical Specialty of Pediatric Respiratory Medicine, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China Liu Liu Department of Pediatrics, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China Lili Zhu Discipline of Pediatric Respiratory Medicine, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China Haiyan Li Discipline of Pediatric Respiratory Medicine, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China Youyou Shao Discipline of Pediatric Respiratory Medicine, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China Hailin Zhang Discipline of Pediatric Respiratory Medicine, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China Gang Yu Discipline of Pediatric Respiratory Medicine, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China 2017 11 21 2018 05 06 Obese asthma is a new asthma phenotype. The underlying mechanisms are not clearly understood. Leptin and adiponectin are two predominant adipokines produced by adipose tissue. Studies have demonstrated a role of leptin on regulating the Janus kinase/signal transducer and ativator of transcription protein (JAK/STAT) signaling pathway and STAT3, STAT6 were known to have essential role on inflammatory cytokines production. However, whether STAT3 and STAT6 are activated and related to leptin merit further investigation. The aim of this study was to investigate the expression levels of leptin/adiponectin ratio and the activations of STAT3 and STAT6 in the lungs of obese asthma mice. Experiments were carried out on male C57/B6J mice. The proteins in bronchoalveolar lavage fluid (BALF) were measured using ELISA. The expression levels of the transcriptional and translational factors in the lungs were examined using Quantitative Reverse Transcriptase Polymerase Chain reaction (qRT-PCR) and western blot. The expression levels of leptin in the BALF of normal weight group, asthma group, obese group and obese asthma group were 2.032±0.133, 5.375±0.123, 5.418±0.165 and 7.486±0.168, respectively. The expression of leptin in obese asthma group was the highest (p<0.05) ，while the expression of adiponectin the lowest (p<0.05). The expression level of P-STAT3 in the obese asthma group was 0.9244±0.014, and was significantly higher than three other groups (p<0.05). The expressions of P-STAT6 in three other groups were all significantly higher than normal weight group (p<0.05). Our data suggest that the function of leptin on the pulmonary inflammation of obese asthma may be partly through activating the STAT3 signaling pathway. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/1739 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/1739/1387

Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 18 1 2019 02 24 72 79 EN Mohsen Khosravi Department of Biochemistry, Iran University of Medical Sciences, Tehran, Iran Mohammad Najafi Department of Biochemistry, Iran University of Medical Sciences, Tehran, Iran AND Molecular and Cellular Research Center, Iran University of Medical Sciences, Tehran, Iran Abdollah Amirfarhangi Department of Cardiology, Hazrat Rasool Akrsm Hospital, Iran University of Medical Sciences, Tehran, Iran Mahdi Karimi Department of Medical Nanotechnology, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran Fahimeh Fattahi Oncopathology Research Center, Iran University of Medical Sciences, Tehran, Iran AND Department of Molecular Medicine, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran Mohammad Shabani Department of Biochemistry, Iran University of Medical Sciences, Tehran, Iran 2018 05 01 2018 07 03 Atherosclerosis is developed due to the formation of atheroma plaques in the coronary arteries. In this process, M1 macrophages and vascular smooth muscle cells (VSMCs) are the main functional cells. Inflammatory mediators such as histamine may inflame M1 macrophages. The aim of this study was to determine the effect of M1 macrophage secretion contents on the gene and protein expression levels of focal adhesion kinase (FAK), vasodilator-stimulated phosphoprotein (VASP), and thrombospondin1 (THBS1). Whole blood samples from the six healthy subjects (stenosis<5%), and six patients (stenosis>70%) were prepared and peripheral blood mononuclear cells (PBMCs) were isolated. Then monocytes were differentiated into M1 macrophages using 100 ng/mL granulocyte-macrophage colony stimulating factor (GM-CSF). The differentiated M1 macrophages were treated with histamine (10-6 M), and their secretion contents were harvested and added to the culture medium of VSMCs. The FAK, VASP, and THBS1 gene expression and protein levels were measured using RT-qPCR and western blot techniques in VSMCs, respectively. The FAK and THBS1 gene expression levels significantly increased in VSMCs after adding secretion contents obtained from histamine-treated M1 macrophages (p=0.023 and 0.05, respectively), while significant results were not observed for VASP gene (p=0.45). In converse with the phosphorylated VASP (pVASP) (p<0.34), the phosphorylated FAK (pFAK) and THBS1 protein levels increased in VSMCs (p<0.001). We concluded that in inflammatory conditions, the immune events could affect the macrophages by histamine. The activated macrophages could locally activate signaling pathways via FAK and THBS1 genes that are effective in the proliferation and migration of VSMCs. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/1943 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/1943/1393

Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 18 1 2019 02 24 80 90 Sarvenaz Kashefi Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran Hamid Ahmadi Breast Disease Research Center (BDRC), Tehran University of Medical Sciences, Tehran, Iran Ramesh Omranipour Breast Disease Research Center (BDRC), Tehran University of Medical Sciences, Tehran, Iran AND Department of Surgical Oncology, Tehran University of Medical Sciences, Tehran, Iran Habibollah Mahmoodzadeh Department of Surgical Oncology, Tehran University of Medical Sciences, Tehran, Iran Fahimeh Jafarnezhad-Ansariha Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran Farzaneh Tofighi Zavareh Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran AND Department of Surgical Oncology, Tehran University of Medical Sciences, Tehran, Iran Abbas Mirshafiey Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran AND Research Center for Immunodeficiencies, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran 2018 09 28 2018 12 03 With respect to the role of chronic inflammation in the induction and progression of breast cancer (BC). The relationship between tumor and tumor microenvironment may be a hopeful strategy for BC therapy. According to the effect of β-D-Mannuronic acid (M2000) as a novel non-steroidal anti-inflammatory drug (NSAID) on BC murine model and 4T1 cell line, we started to study that was a phase II, randomized, controlled clinical trial. 24 women with BC were included in this study and were followed by fixed oral doses of M2000, 500 mg two times a day (6-8 weeks). Blood samples were collected at baseline and weeks 6-8. To compare the patterns of matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9), C-C motif chemokine ligand 22 (CCL22) and The transforming growth factor-beta 1 (TGFβ1) gene expression and T regulatory cells (Tregs) frequency of healthy women normal controls with BC patients, a set of 10 blood samples of  women healthy volunteers was collected. The gene expression was evaluated by quantitative Real-time PCR (qRT-PCR) and the frequency of Tregs was assessed by flow cytometry. Our results showed, reduction in MMP-2 (p=0.08), MMP-9 (p=0.03), CCL22 (p=0.003) and TGFβ1 (p=0.1) gene expression and Tregs frequency (p=0.01) which play a main role in the development of chronic inflammation, angiogenesis, tumorigenesis and metastasis. Our findings demonstrated that M2000 therapy as a novel designed NSAID had valuable therapeutic effects on BC. No adverse effects were observed following the use of M2000 after 6-8 weeks. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/2157 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/2157/1401

Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 18 1 2019 02 24 91 99 EN Fateme Hesampour Department of Immunology, Shiraz University of Medical Sciences, Shiraz, Iran Bahia Namavar Jahromi Infertility Research Center, Shiraz University of Medical Sciences, Shiraz, Iran AND Department of Gynecology and Obstetrics, Shiraz University of Medical Sciences, Shiraz, Iran Foroozan Tahmasebi Department of Immunology, Shiraz University of Medical Sciences, Shiraz, Iran Behrouz Gharesi-Fard Department of Immunology, Shiraz University of Medical Sciences, Shiraz, Iran AND Infertility Research Center, Shiraz University of Medical Sciences, Shiraz, Iran 2018 10 31 2018 12 29 Polycystic ovary syndrome (PCOS) is correlated with low-grade chronic inflammation. Interleukin-17A (IL-17A) and Interleukin-32 (IL-32) are two members of the pro-inflammatory cytokines which act as significant components of the immune system during certain inflammatory diseases. Along with immunological processes, genetic factors play major roles in predisposition to PCOS. There are myriad single nucleotide polymorphisms (SNPs) within IL-17A and IL-32 genes that may affect their production and the susceptibility of individuals to PCOS. The objective of the present research was to investigate the association between IL-17A (rs2275913) and IL-32 (rs9927163, rs4786370) SNPs, and also their serum levels with susceptibility to PCOS in a group of Iranian women. In this case-control study, 150 PCOS patients (mean age of 29.1 years) and 150 healthy women (mean age of 26.1 years) were analyzed in terms of IL-17A and IL-32 SNPs via polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. Furthermore, serum levels of IL-17A and IL-32 cytokines were measured through the use of ELISA method. There were significant differences between PCOS and healthy women regarding IL-17A rs2275913 alleles, genotypes frequencies (p=0.005, and 0.01, respectively) and the allelic distribution of IL-32 rs9927163 SNP (p=0.03). Additionally, significant differences were indicated between two groups concerning the AG genotype against AA+GG genotypes (p=0.009) and the GG genotype against AA+AG genotypes (p=0.006) in IL-17A rs2275913 SNP. In the matter of IL-32 gene SNPs, GC haplotype frequency was significantly different between patients and controls (p=0.05). Furthermore, IL-32 serum level was not significantly different between the two studied groups and the serum level of IL-17A was not detectable. In conclusion, IL-17A and IL-32 SNPs might be associated with predisposition to PCOS in Iranian women. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/2180 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/2180/1397

Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 18 1 2019 02 24 100 107 EN Fatemeh Vafashoar Department of Immunology, Iran University of Medical Sciences, Tehran, Iran Hadi Poormoghim Scleroderma Study Group, Firoozgar Hospital, Iran University of Medical Sciences, Tehran, Iran Kazem Mousavizadeh Department of Molecular Medicine, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran Tahereh Mousavi Shabestari Institute of Immunology and Infectious Disease, Antimicrobial Resistance Research Center, Tehran, Iran Abbas Tavasoli Department of Pathobiology, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran Seyed Ali Javadmoosavi Air Pollution Research Centre, School of Public Health, Iran University of Medical Sciences, Tehran, Iran Nazanin Mojtabavi Department of Immunology, Iran University of Medical Sciences, Tehran, Iran 2018 02 04 2018 06 18 Systemic sclerosis is a female predominant, a fibrotic autoimmune disease in which disturbance in tissue homeostasis and cell turnover including cell apoptosis are central events in pathogenesis. Sex hormones are known as the important players in sexual dimorphism of autoimmune diseases and in tissue homeostasis. Progesterone influences autoimmune disease via its immunomodulatory effect or by its direct action on parenchymal cell function. On the other hand, this hormone impacts tissue homeostasis by acting on cell apoptosis in a different situation. The objective of this study was to examine the effect of progesterone on cellular apoptosis of skin and lung tissues in a mouse model of scleroderma. Four group of mice were involved in this study with 10 mice in each. The fibrotic model was induced by daily subcutaneous injection of bleomycin for 28 days. One week after initiation of fibrosis induction, mice received subcutaneous progesterone alone or with bleomycin for 21 days. Control group received only Phosphate buffered saline PBS. After 28 days, under lethal anesthesia skin and lung tissues were harvested for histological assessment and hydroxyproline measurement. Apoptosis in tissue sections was detected by TUNEL assay technique. Bleomycin administration induced fibrosis in skin and lung tissues. Severe apoptosis was seen in skin and lung tissues of the bleomycin-treated group (p<0.001 in the skin and p<0.05 in the lung). Progesterone injection either in the skin (p>0.05) or in the lung (p>0.05) did not alter apoptosis in bleomycin-treated animals. Our data confirm the role of apoptosis in the pathogenesis of fibrosis in this model; however, progesterone does not affect cellular apoptosis in skin and lung tissues of bleomycin-injured animals. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/1857 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/1857/1395

Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 18 1 2019 02 24 108 113 EN Maryam Azimi Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran AND Immunology Research Center, Iran University of Medical Sciences, Tehran, Iran Mojdeh Ghabaee Department of Neurology, Iranian Center of Neurological Research, Imam Khomeini Hospital, Tehran University of Medical Sciences, Tehran, Iran Abdolreza Naser Moghadasi Multiple Sclerosis Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran Maryam Izad Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran AND Multiple Sclerosis Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran 2018 03 06 2018 06 03 Invasion of auto-reactive CD4+ T cells especially Th17 into central nervous system (CNS) is an underlying pathogenic mechanism in multiple sclerosis (MS). CD4+ T cells release exosomes which are enriched in microRNAs, reflective of cell’s physiological or pathological condition. Thus exosomes could be potent agents to provide quantitative and qualitative information about involved cells in MS. We investigated the expression of pathogenic microRNAs in T cells-derived exosomes of MS patients or healthy controls. Conventional T cells (Tconv) derived from relapsing-remitting (RR) MS patients (n=10) and healthy controls (n=10) were purified and cultured for 3 days by soluble anti-CD3/CD28. Exosomes were purified from cultured-T cells supernatants. The expression levels of exosomal miR-146a, miR-29a, miR-155, and miR-326 were quantified by real-time PCR. A statistically significant increased expression of miR-326 in Tconv-derived exosomes was observed in RRMS patients as compared with controls (7.5±1.88vs 2.51±0.9 p=0.03), On the contrary, no differences were found in the expression levels of miR-155, miR-146a, and miR-29a, in Tconv-derived exosomes of  patients as compared with controls (p>0.05). Our results point to altered expression in exosome-derived microRNAs. MiR-326 was previously shown to play a role in the immunopathogenesis of MS by inducing TH17 differentiation and maturation. Therefore, miR-326 containing exosomes might also be a potential clinical target in course of MS. Moreover, the deregulation of this miRNA in exosomes may serve as a diagnostic and prognostic biomarker.  https://ijaai.tums.ac.ir/index.php/ijaai/article/view/1891 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/1891/1399

Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 18 1 2019 02 24 114 119 EN Rasoul Baharlou Cancer Research Center, Semnan University of Medical Sciences, Semnan, Iran AND Department of Immunology, School of Medicine, Semnan University of Medical Sciences, Semnan, Iran Nesa Rashidi Department of Immunology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran Abbas Ahmadi-Vasmehjani Department of Immunology and Microbiology, School of Medicine, Jahrom University of Medical Sciences, Jahrom, Iran Mahshid Khoubyari Department of Student Research Committee, School of Medicine, Jahrom University of Medical Sciences, Jahrom, Iran Maryam Sheikh Department of Immunology, School of Medicine, Semnan University of Medical Sciences, Semnan, Iran Saiedeh Erfanian Research Center for Non-Communicable Diseases, School of Medicine, Jahrom University of Medical Sciences, Jahrom, Iran 2018 06 15 2018 09 25 Adipose-derived mesenchymal stem cells (Ad-MSCs) have been reported to suppress the effector T cell responses and have beneficial effects on various immune disorders, like rheumatoid arthritis (RA). This study was designed to investigate the effects of co-cultured Ad-MSCs on peripheral blood mononuclear cells (PBMCs) of RA patients and healthy individuals, through assessing transcription factors of T cell subsets. PBMCs from RA patients and healthy donors were co-cultured with Ad-MSCs with or without Phytohaemagglutinin (PHA). The quantitative real-time polymerase chain reaction (qRT-PCR) was used to measure the expression of T-box 21 (T-bet), GATA-binding protein-3 (GATA3), retinoid-related orphan receptor γt (ROR-γt) and forkhead box P3 (Foxp3). Based on the results, Ad-MSCs greatly upregulated Th2 and Treg cell transcription factors, i.e., GATA3 and Foxp3 (p<0.05), and downregulated Th1 and Th17 transcription factors, i.e., T-bet and RORγt (p<0.05). These results demonstrate that Ad-MSCs can result in an immunosuppressive environment through inhibition of pro-inflammatory T cells and induction of T cells with a regulatory phenotype. Therefore, they might have important clinical implications for inflammatory and autoimmune diseases such as RA. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/1999 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/1999/1400