Iranian Journal of Allergy, Asthma and Immunology http://ijaai.tums.ac.ir/index.php/ijaai Tehran University of Medical Sciences en-US Iranian Journal of Allergy, Asthma and Immunology 1735-1502 The Stimulatory Effects of Medicinal Plants on β2-Adrenoceptors of Tracheal Smooth Muscle http://ijaai.tums.ac.ir/index.php/ijaai/article/view/1803 <p>Medicinal plants have been identified and used as primary sources in prevention and&nbsp;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 β<sub>2</sub>-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, β<sub>2</sub>-adrenoceptors, possible mechanism, tracheal smooth muscle (TSM), medicinal plants and their constituents as keywords from 1985 to 2017. All studied plants including; <em>Nigella sativa, Rosa damascena, Thymus vulgaris, Carum</em> <em>copticom,</em> <em>Carum carvi,</em> <em>Zataria multiflora, Crocus sativus,</em> <em>Cuminum</em> <em>cyminum</em><em>, </em><em>Liomnia</em> <em>acidissima</em><em>, Portulaca</em> <em>oleraceae,</em> <em>Satureja</em> <em>hortensis, </em><em>Ephedra sinica</em> and <em>Achillea</em> <em>millefolium</em> showed relaxant effect on tracheal smooth muscle with a stimulatory effect on β<sub>2</sub>-adrenoceptors mechanism. The studied plants and their constituents could be of therapeutic value in clinical practice as a bronchodilatory drug by β<sub>2</sub>-adrenoceptors stimulatory mechanism for treatment of obstructive pulmonary diseases.</p> Farzaneh Shakeri Vahideh Ghorani Saeideh Saadat Zahra Gholamnezhad Mohammad Hosein Boskabady ##submission.copyrightStatement## 2018-12-03 2018-12-03 1 15 The Review of In Vitro and In Vivo Studies over the Glycyrrhizic Acid as Natural Remedy Option for Treatment of Allergic Asthma http://ijaai.tums.ac.ir/index.php/ijaai/article/view/1740 <p>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 "&nbsp;liquorice root" OR "G. glabra" OR "glycyrrhizic Acid" AND "allergic asthma"&nbsp; OR "bronchial asthma" OR "asthma, bronchial" OR "airway hyper-responsiveness" OR "airway inflammation".&nbsp;&nbsp;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.</p> Saloomeh Fouladi Mohsen Masjedi Mazdak Ganjalikhani Hakemi Nahid Eskandari ##submission.copyrightStatement## 2019-01-22 2019-01-22 1 11 Th9 Cells As a New Player in Inflammatory Skin Disorders http://ijaai.tums.ac.ir/index.php/ijaai/article/view/1788 <p>CD4<sup>+</sup>T cells are composed of different subpopulations that differ in developmental pathways, surface markers, and their products. Among the catalog of these cells is Th9 cell subset that has a great capacity of Interleukin (IL)-9 production. They could be involved in the pathogenic or protective immune responses. Therefore, it is important to know how Th9 cells and cytokines influence the function of the human immune system as multitasking machinery, both in isolation or after the interaction with other surrounding cells. Since an important characteristic of Th9 cells is their tropism for skin, this article reviews the physiological and pathophysiological functions of Th9 and its cytokines under normal conditions and inflammatory skin disorders.</p> Zohreh Jadali ##submission.copyrightStatement## 2019-01-30 2019-01-30 1 11 Recent Advances in Gene Therapy and Modeling of Chronic Granulomatous Disease http://ijaai.tums.ac.ir/index.php/ijaai/article/view/1868 <p>The <em>Chronic granulomatous disease</em> (CGD) is a primary immunodeficiency that characterized by mutations in phagocyte nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, resulting in deficient antimicrobial activity of phagocytic cells and recurrent childhood infections. Hematopoietic stem cell transplantation (HSCT) is a curative option for patients with human leukocyte antigen (HLA) matched donor, when conventional cares and therapies fail. However, in many cases when the patients have not an HLA-matched donor, they need to a method to recapitulate the function of the affected gene within the patient’s own cells. Gene therapy is a promising approach for CGD. While, the success of retroviral or lentiviral vectors in gene therapy for CGD has been hampered by random integration and insertional activation of proto-oncogenes. These serious adverse events led to improvement and generations of viral vectors with increased safety characteristics. Gene therapy continues to progress and the advent of new technologies, such as engineered endonucleases that have shown a great promise for the treatment of genetic disease. This review focuses on the application of gene therapy for the CGD, the limitations encountered in current clinical trials, advantages and disadvantages of endonucleases in gene correction and modeling with CRISPR/Cas9 approach.</p> Arefeh Jafarian Gelareh Shokri Mahdieh Shokrollahi Barough Mostafa Moin Zahra Pourpak Masoud Soleimani ##submission.copyrightStatement## 2019-01-30 2019-01-30 1 12 Expression Levels of Predominant Adipokines and Activations of STAT3, STAT6 in an Experimental Mice Model of Obese Asthma http://ijaai.tums.ac.ir/index.php/ijaai/article/view/1739 <p>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&nbsp; 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 (<em>p</em>&lt;0.05) ,while the expression of adiponectin the lowest (<em>p</em>&lt;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 (<em>p</em>&lt;0.05). The expressions of P-STAT6 in three other groups were all significantly higher than normal weight group (<em>p</em>&lt;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.</p> Lei Chong Liu Liu Lili Zhu Haiyan Li Youyou Shao Hailin Zhang Gang Yu ##submission.copyrightStatement## 2019-01-22 2019-01-22 1 10 Beneficial Effects of Hydroalcoholic Extract of Saffron in Alleviating Experimental Autoimmune Diabetes in C57bl/6 Mice http://ijaai.tums.ac.ir/index.php/ijaai/article/view/1886 <p>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 <em>p</em>&lt;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.</p> Shole Faridi Norouz Delirezh Seyyed Meysam Abtahi Froushani ##submission.copyrightStatement## 2019-01-22 2019-01-22 1 10 The Levels of Serum Biomarkers in Stable Asthma Patients with Comorbidities http://ijaai.tums.ac.ir/index.php/ijaai/article/view/1750 <p>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 (<em>p</em> values were&nbsp; 0.032 and 0.046, respectively).&nbsp;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.&nbsp;</p> Emel Ceylan Sertan Bulut Mustafa Yilmaz Hüseyin Örün Fisun Karadağ İmran Kurt Ömürlü Sevin Kirdar Aslıhan Karul ##submission.copyrightStatement## 2019-01-30 2019-01-30 1 11 The Increase of pFAK and THBS1 Protein and Gene Expression Levels in Vascular Smooth Muscle Cells by Histamine-treated M1 Macrophages http://ijaai.tums.ac.ir/index.php/ijaai/article/view/1943 <p>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&lt;5%), and six patients (stenosis&gt;70%) were prepared and peripheral blood mononuclear cells (PBMCs) were isolated. Then monocytes were differentiated into M1 macrophages using 100 ng/mL granulocyte<strong>-</strong>macrophage colony stimulating factor (GM-CSF). The differentiated M1 macrophages were treated with histamine (10<sup>-6</sup> 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 (<em>p=</em>0.023 and 0.05, respectively), while significant results were not observed for VASP gene (<em>p=</em>0.45). In converse with the phosphorylated VASP (pVASP) value (P 0.34), the phosphorylated FAK (pFAK) and THBS1 protein levels increased in VSMCs (<em>p</em>&lt;0.001). We concluded that in inflammatory conditions, the immune events could affect the macrophages by histamine. The activated macrophages could locally activate signaling&nbsp;pathways via FAK and THBS1 genes that are effective in the proliferation and migration of VSMCs.</p> Mohsen Khosravi Mohammad Najafi Abdollah Amirfarhangi Mahdi Karimi Fahimeh Fattahi Mohammad Shabani ##submission.copyrightStatement## 2019-01-30 2019-01-30 1 8 Effect of High-fat Diet on Tracheal Responsiveness to Methacholine and Insulin Resistance Index in Ovalbumin-sensitized Male and Female Rats http://ijaai.tums.ac.ir/index.php/ijaai/article/view/1874 <p>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 EC<sub>50</sub> (the effective concentration of methacholine generating 50% of peak response) in F+SHFD rats was statistically lower than M+SHFD group (<em>p</em>&lt;0.05). Moreover, insulin resistance was higher in the F+SHFD than the M+SHFD group (<em>p</em>&lt;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.</p> Hassan Ghobadi Mohammad Reza Alipour Rana Keyhanmanesh Mohammad Hossein Boskabady Mohammad Reza Aslani ##submission.copyrightStatement## 2019-02-04 2019-02-04 1 14 The Role of Progesterone in Cellular Apoptosis of Skin and Lung in a Bleomycin-injured Mouse Model http://ijaai.tums.ac.ir/index.php/ijaai/article/view/1857 <p>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 (<em>p</em>&lt;0.001 in the skin and <em>p</em>&lt;0.05 in the lung). Progesterone injection either in the skin (<em>p</em>&gt;0.05) or in the lung (<em>p</em>&gt;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.</p> Fatemeh Vafashoar Hadi Poormoghim Kazem Mousavizadeh Tahereh Mousavi Shabestari Abbas Tavasoli Sayed Ali Javadmoosavi Nazanin Mojtabavi ##submission.copyrightStatement## 2019-02-05 2019-02-05 1 8 Association between Interleukin-32 and Interleukin-17A Single Nucleotide Polymorphisms and Serum Levels with Polycystic Ovary Syndrome http://ijaai.tums.ac.ir/index.php/ijaai/article/view/2180 <p>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 (<em>p</em>=0.005, and 0.01, respectively) and the allelic distribution of IL-32 rs9927163 SNP (<em>p</em>=0.03). Additionally, significant differences were indicated between two groups concerning the AG genotype against AA+GG genotypes (<em>p</em>=0.009) and the GG genotype against AA+AG genotypes (<em>p</em>=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 (<em>p</em>=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.</p> Fateme Hesampour Bahia Namavar Jahromi Foroozan Tahmasebi Behrouz Gharesi-Fard ##submission.copyrightStatement## 2019-02-05 2019-02-05 1 9 Altered Expression of miR-326 in T Cell-Derived Exosomes of Patients with Relapsing-Remitting Multiple Sclerosis http://ijaai.tums.ac.ir/index.php/ijaai/article/view/1891 <p><strong>Background/Aim</strong>: Multiple sclerosis (MS) is an immune-mediated neurodegenerative disease of central nervous system (CNS). Invasion of autoreactive CD4<sup>+</sup> T cells into CNS is believed to be an underlying pathogenic mechanism in MS. CD4+ T cells release exosomes which are highly enriched in microRNAs, reflective of physiological or pathological condition. Exosomal microRNAs are transferred between cells and affect the physiology of target cells. Thus exosomes could be potent agents to provide quantitative and qualitative information about immune cells involved in MS. We investigated the expression of pathogenic microRNAs in T cells-derived exosomes of MS patients or healthy controls.</p> <p><strong>Methods:</strong>&nbsp; Conventional T cells (Tconv) derived from relapsing-remitting (RR) MS patients or healthy controls were cultured for 3 days by soluble anti-CD3/CD28. Exosomes were purified from supernatants. After RNA extraction from exosomes pellet, the expression levels of miR-146a, miR-29a, miR-155, and miR-326 were quantified by real-time PCR.</p> <p><strong>Result</strong>: A statistically significant increased expression of miR-326 in&nbsp; 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 &nbsp;patients as compared with controls (P&gt;0.05).&nbsp;</p> <p><strong>Conclusion: </strong>Our results point to an 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.</p> Maryam Azimi Mojdeh Ghabaee Abdolreza Nasermoghadasi Maryam Izad ##submission.copyrightStatement## 2019-02-16 2019-02-16 1 11