Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 10 3 2011 09 15 147 154 EN Maryam Adelipour Chemical Injury Research Center (CIRC), Baqiyatallah University of Medical Sciences, Tehran, Iran Abbas Ali Imani Fooladi Applied Microbiology Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran Samaneh Yazdani Chemical Injury Research Center (CIRC), Baqiyatallah University of Medical Sciences, Tehran, Iran Ensieh Vahedi Chemical Injury Research Center (CIRC), Baqiyatallah University of Medical Sciences, Tehran, Iran Mostafa Ghanei Chemical Injury Research Center (CIRC), Baqiyatallah University of Medical Sciences, Tehran, Iran Mohammad Reza Nourani Chemical Injury Research Center (CIRC), Baqiyatallah University of Medical Sciences, Tehran, Iran 2015 10 01 Airway remodelling is characterized by the thickening and reorganization of the airways seen in mustard  lung patients. Mustard lung is the  general description  for  the  chronic obstructive  pulmonary  disease induced  by  sulfur  mustard(SM). Pulmonary  disease was diagnosed as the most important  disorder in individuals that had been exposed to sulfur mustard. Sulfur mustard is a chemical warfare agent developed during Wars. Iraqi forces frequently used it against Iranian during Iran –Iraq in the 1980–1988. Peribronchial fibrosis result  from  airway remodeling  that  include  excess  of  collagen of  extracellular matrix deposition  in  the  airway wall. Some of  Smads families in  association with TGF-β  are involved in airway remodeling due to lung fibrosis. In the present study we compared the mRNA expression of Smad2, Smad3, and Smad4 and Smad7 genes in airway wall biopsies of chemical-injured patients with non-injured patients as control. We used airway wall biopsies of ten unexposed patients and fifteen SM-induced patients. Smads expression was evaluated by RT-PCR followed by bands densitometry. Expression levels of Smad3 and Smad4 in SM exposed patients were upregulated but Smad2 and Smad7 was not significantly altered. Our results revealed that Smad3, and 4 may be involved in airway remodeling process in SM induced  patients  by  activation of  TGF-β.  Smad pathway is  the  most  represented signaling mechanism for  airway remodeling and  peribronchial fibrosis. The  complex of Smads in the nucleus affects a series of genes that results in peribronchial fibrosis in SM- induced patients. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/305 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/305/305

Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 10 3 2011 09 15 155 161 EN Maryam Mohajeri Department of Cell & Mol. Biology, School of Biology, Faculty of Science, University of Tehran, Tehran, Iran Ali Farazmand Department of Cell & Mol. Biology, School of Biology, Faculty of Science, University of Tehran, Tehran, Iran Mandana Mohyeddin Bonab Molecular Immunology Research Center, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran Behrooz Nikbin Molecular Immunology Research Center, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran Alireza Minagar Department of Neurology, Louisiana State University Health Sciences Center, Shreveport, LA, USA 2015 10 01 Multiple Sclerosis (MS) is an inflammatory demyelinating and neurodegenerative disorder of  the  central  nervous  system (CNS), which mainly affects  young adults. Activated T lymphocytes promote the neuro-inflammatory cascade of MS by secreting pro-inflammatory cytokines and play a significant role in its pathogenesis. T  lymphocytes may trigger the inflammation, which in turn leads to axonal loss and neurodegeneration observed in the course of MS. Currently, there is no cure for MS, however, one of the most promising neuroprotective research tools consists of the use of bone marrow derived mesenchymal stem cells (MSC). This method promotes immune system regulation and possibly induces neurological repair and re-myelination of the damaged axons. Recent studies have shown that MSC exert an immune regulatory function  and induce T regulatory-cell proliferation, therefore,  it may serve as a potentially useful treatment for immune-mediated diseases such as MS. In this pilot study a group of MS patients underwent MSC therapy and we assayed the expression of an X-linked transcription factor, FoxP3, as a specific marker of T Regulatory cells in peripheral blood, prior to and after the treatment. Using q RT-PCR for measurement of expression of FoxP3 by peripheral blood mononuclear cells, we found that in all subjects, except for one, the expression of FoxP3 at 6 months after intrathecal injection of MSC was significantly higher than the levels prior to treatment. Such significant enhanced expression of FoxP3 associated with clinical stability. Findings from  this  pilot  study further  support  the  potential  of  bone  marrow  derived MSC for treatment of MS patients. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/306 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/306/306

Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 10 3 2011 09 15 163 170 EN Ghasem Mosayebi Molecular and Medicine Research Center, Department of Immunology, School of Medicine, Arak University of Medical Sciences, Arak, Iran AND Department of Immunology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran Seyed Mohammad Moazzeni Department of Immunology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran 2015 10 01 Dendritic cells (DCs) play an important role in induction of cellular immune responses. It seems that DCs that reside in different organs may be distinct in their ability to  induce immune responses. This study was done to address the differences between spleen and liver DCs in induction of immune response and/or tolerance. CD11c+  DCs were separated from the liver and spleen of C57BL/6 mice and pulsed with myelin oligodendrocyte glycoprotein (MOG) peptide 35-55. 6×105 MOG35-55 pulsed spleen or liver DCs were injected in foot pad of different groups of mice. Control groups received unpulsed DCs. After 5 days, the mononuclear cells (MNCs) of the regional lymph nodes were isolated from immunized mice for cytokine assays and lymphocyte transformation test. To study the immunologic or tolerogenic effects of DCs, three weeks after immunization of mice with MOG  pulsed liver or spleen DCs, experimental autoimmune encephalomyelitis (EAE)  was induced in DC-immunized mice by injection of MOG  along with complete Freund’s adjuvant. Our  results showed that spleen DCs were more potent  in stimulating lymph  node  T  cells as  illustrated in  lymphocyte transformation  test.  Moreover  IL-10 production was higher in mice immunized with liver DCs compared with those immunized with splenic DCs (p=0.017). However, no significant difference in IFN-γ  production  was observed  between  two  groups.  We also found  that  liver DCs+MOG  immunized mice displayed a significantly delayed disease onset compared with spleen DCs+MOG immunized mice and the control groups. The disease score was also milder in liver DCs immunized mice compared with other groups. It seems that the higher IL-10 production induced by the liver DCs may be one of the main factors in down regulation of immune responses in this organ. It can be concluded also that the liver DCs may inhibit the progress of EAE by shifting the cytokines profile. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/307 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/307/307

Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 10 3 2011 09 15 171 182 EN Yi Liu Department of Respiratory Medicine, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410011, China Gu-yi Wang Department of Respiratory Medicine, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410011, China Shao-kun Liu Department of Respiratory Medicine, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410011, China Mu-yi Yang Department of Respiratory Medicine, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410011, China Li-bing Ma Department of Respiratory Medicine, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410011, China Keng Li Department of Respiratory Medicine, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410011, China Su-bo Gong Department of Respiratory Medicine, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410011, China Li Zhang Department of Respiratory Medicine, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410011, China Ping Chen Department of Respiratory Medicine, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410011, China Xu-dong Xiang Department of Respiratory Medicine, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410011, China 2015 10 01 Allergic asthma is a complex and chronic inflammatory airway disease. Interleukin-17 is a pro-inflammatory cytokine which plays critical role in the pathogenesis of allergic asthma. It has been reported that β-arrestin2 regulated the development of allergic asthma at a proximal step in the inflammatory cascade. In this study, the influence of β-arrestin2 on Interleukin-17 production and expression of CD4+  T lymphocytes in a murine asthma model was investigated. Splenic CD4+   T lymphocytes from  wild-type mice and those  from  a murine asthma model were purified. CD4+  T lymphocytes from a murine asthma model were transfected with  siRNAs  targeting the  β-arrestin2  or  were pretreated  with  the  ERK1/2  inhibitor,PD98059.  After  stimulation,  the   protein   expression  of   β-arrestin2、phosphorylated- ERK1/2 and IL-17 were detection by Western blot; the mRNA expression of IL-17 were detected by real-time PCR; the accumulation of IL-17 in supernatants  were detected by ELISA. We found that β-arrestin2、phosphorylated-ERK1/2 and IL-17 expression in CD4+  T lymphocytes from a murine asthma model was increased compared with those from wild- type mice(p<0.01). Treatment of CD4+  T lymphocytes with siRNAs targeting the β-arrestin2 down-regulated phosphorylated-  ERK  1/2  and  IL-17 expression  (p <  0.01). PD98059 decreased IL-17 production  and expression in CD4+   T lymphocytes in a murine asthma model (p < 0.05). We conclude that β-arrestin2 stimulated IL-17 production  and expression of CD4+   T lymphocytes in a murine  asthma  model. The  effect  was partly mediated  by ERK  1/2 activation. Targeting β-arrestin2 biological activity could be a valid therapeutic approach for the treatment of allergic asthma. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/308 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/308/308

Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 10 3 2011 09 15 183 188 EN Giorgio Ciprandi Department of Internal Medicine, Azienda Ospedaliera Universitaria San Martino, Genoa, Italy Mara De Amici Pediatric Clinic- University of Pavia-Foundation IRCCS San Matteo, Pavia, Italy Mariangela Tosca Pneumology and Allergy Unit, Istituto Giannina Gaslini, Genoa, Italy Roberta Alesina Pneumology, Foundation IRCCS San Matteo, Pavia, Italy Gianluigi Marseglia Pediatric Clinic- University of Pavia-Foundation IRCCS San Matteo, Pavia, Italy Dietmar Fuchs Division of Biological Chemistry, Biocenter, Innsbruck Medical University, Innsbruck, Austria 2015 10 01 Allergic rhinitis (AR) is a very frequent disease which is not only characterized by nasal symptoms, but also with behavioural changes. This study evaluated the serum serotonin levels in patients with pollen-induced AR during and outside the pollen season. One-hundred-two  (56 females, 46 males, median age: 28.7 years) were included in this study: 56 with seasonal AR (SAR) evaluated outside the pollen season and so without allergic inflammation and symptoms, and 46 with SAR evaluated during the pollen season with symptoms. Blood specimens were collected to assess serum concentrations of serotonin and to compare results to scores of a Quality of Life (QoL) questionnaire which was performed in all subjects. Serotonin serum concentrations were higher in AR patients out of pollen season than in (p<0.01). There was a very strong direct relationship between QoL and serotonin concentrations. This preliminary study demonstrates that SAR influences serotonin concentrations and that serum serotonin could serve as a biomarker in AR patients with behavioural symptoms. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/309 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/309/309

Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 10 3 2011 09 15 189 194 EN Tahereh Mousavi Department of Immunology, Tehran University of Medical Sciences, Tehran, Iran AND Microbial Resistance Research Center, Tehran University of Medical Sciences, Tehran, Iran AND Immunology Research Center, Tehran University of Medical Sciences, Tehran, Iran Parisa Farnia Mycobacteriology Research Center (NRITLD), Massih Daneshvary Hospital, Tehran, Iran Nader Tajik Department of Immunology, Tehran University of Medical Sciences, Tehran, Iran AND Immunology Research Center, Tehran University of Medical Sciences, Tehran, Iran Mahbubeh Soofi Department of Microbiology, Ghom University of Medical Sciences, Ghom, Iran Farhad shahsavar Department of Immunology, Lorestan University of Medical Sciences, Khorram Abad, Iran 2015 10 01 Analysis of  receptor–ligand  interactions  in  the  context  of  diseases  necessitates  to understand how HLA–KIR genotypes function in diseases. Although CD56+  lymphocytes are derived from multiple lineages, they share a functional association with immunosurviellance and antimicrobial responses. The present study aimed to determine whether KIR phenotype in CD56 lymphocytes and corresponding  HLA-class 1 ligands are associated with multidrug resistance tuberculosis (MDR-TB). We compared the frequencies of HLA-C and HLA-BW4 genes, the expression of KIRs 2DL1/2DS1, 2DL2/2DL3, 3DL1, and 2DS4 and the combinations of HLA/KIR in 32 Nifamycin and Isoniazid-resistant TB with those in 68 drug non resistant (NR) sputum smear positive pulmonary TB patients. PCR-SSP and flow cytometry were performed for HLA and KIRs typing, respectively. We showed no significant differences between inhibitory or activating KIRs as well as HLA ligands in MDR TB patients compared with NR-TB . The combinations of inhibitory KIR-HLA ligands in MDR-TB were much more prevalent, but not statistically significant than in NR patients (p=0.07). The frequency of MDR patients with all HLA-C and HLA- BW4 ligands was higher  than  NR-TB  (p<0.009). Conversely, the  percentage  of  MDR patients having only one kind of HLA gene was significantly lower than NR-TB (p<0.01). We conclude that the expression of inhibitory KIRs with corresponding HLA ligands genes, and/or co-existence of three HLA class 1 ligands for inhibitory KIRs may be associated with drug resistance in pulmonary tuberculosis. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/310 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/310/310

Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 10 3 2011 09 15 195 205 EN Rafael Rojo-España Unit of Dermatology, University Hospital “Dr. Peset”, Valencia, Spain Lidia Tomas-Mallebrera Unit of Dermatology, University Hospital “Dr. Peset”, Valencia, Spain Natalia Gimeno-Clemente CIBER Epidemiology and Public Health (CIBERESP), Spain AND Unit of Public Health and Environmental Care, Department of Preventive Medicine, University of Valencia, Valencia, Spain Amparo Marquina-Vila Unit of Dermatology, University Hospital “Dr. Peset”, Valencia, Spain María Morales-Suárez-Varela CIBER Epidemiology and Public Health (CIBERESP), Spain 2015 10 01 Contact dermatitis is frequent skin pathology and eyelids are one of the more frequent locations of this pathology. The objective of the present work was to study the population distribution of periocular dermatitis, determine the allergens which most frequently indicate positive in patch tests and in provocative use tests, and analyse the clinical relevance of the positive tests. Patients with periocular dermatitis (N=93) underwent a thorough physical examination and a patch test with standard series. According to clinical suspicions, 76 patients underwent a patch test with specific series. Finally a provocative use test was done for 36 patients with suspected  products  that  the  patients  brought.  The  tests  were classified according their relevance. The most  frequently observed allergen in the  patch tests (with standard and specific series) was nickel followed by mercury, and anti-glaucoma drops in the provocative use tests with patients products. Patients’ sex, age, occupation, clinical status, presence of associated periocular symptoms, and presence of atopic or seborrheic dermatitis and/or rosacea did not relate with relevance. We conclude that  a clinical diagnosis may not  always be made with patch tests with standard and specific series due to lack of relevance. It is important to do provocative use tests with the products suspected as allergens in those cases where patch tests with standard and specific series indicated positive for more than one allergen. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/311 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/311/311

Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 10 3 2011 09 15 207 220 EN Yajuan Wang Zhejiang Respiratory Drugs Research Laboratory of State Food and Drug Administration of China, College of Medicine, Zhejiang University, Hangzhou 310058, China AND The Center of Function Experiment, Anhui College of Traditional Chinese Medicine, Hefei, 230038, China Yali Jiang Zhejiang Respiratory Drugs Research Laboratory of State Food and Drug Administration of China, College of Medicine, Zhejiang University, Hangzhou 310058, China Huifang Tang Zhejiang Respiratory Drugs Research Laboratory of State Food and Drug Administration of China, College of Medicine, Zhejiang University, Hangzhou 310058, China Xuefeng Wang Zhejiang Respiratory Drugs Research Laboratory of State Food and Drug Administration of China, College of Medicine, Zhejiang University, Hangzhou 310058, China Chunzhen Zhao Zhejiang Respiratory Drugs Research Laboratory of State Food and Drug Administration of China, College of Medicine, Zhejiang University, Hangzhou 310058, China Jiqiang Chen Zhejiang Respiratory Drugs Research Laboratory of State Food and Drug Administration of China, College of Medicine, Zhejiang University, Hangzhou 310058, China 2015 10 01 Phosphodiesterases  (PDE)  hydrolyse intracellular cAMP  and  cGMP  to  inactive  5’ monophosphates. Decreased level of cAMP is involved in the pathogenesis of asthma. We and others have shown that phosphodiesterases were upregulated in the lung of allergic rats, and Bacilli Calmette-Guérin (BCG) induced the production of cAMP in vitro. However, it is unclear how BCG’s effect asthma and whether it is related to PDEs. In  this  study,  BCG  was  intraperitoneally  injected  into  male  Sprague-Dawley rats sensitized and later the rats were challenged with ovabumin/pertusis. The inflammation in lungs was measured. Airway hyperresponsiveness was determined using MedLab software after intravenous methacholine challenge. Furthermore,  cAMP level and adenylate cyclase activity in lungs were analyzed by ELISA, phosphodiesterases activities were analyzed by HPLC, while PDEs mRNA levels in lungs was analyzed by reverse transcription-polymerase chain  reaction.  Administration  of  BCG  significantly attenuated  allergen-induced  lung inflammatory response  and  hyper  responsiveness  as  compared  with  vehicle treatment. Furthermore,  the  levels of  cAMP in lungs were significantly increased in  BCG-treated allergic rats. Interestingly, administration of BCG decreased the activity of cAMP-PDE, but not adenylyl cyclase (AC), activity in lungs of animals. Furthermore, pretreatment with BCG significantly decreased the mRNA levels of PDE4A, 4C, 5 and 8, which were induced in lungs of allergic rats. BCG  administration  attenuated  airway inflammatory  response  and  bronchial  hyper responsiveness in rats, which are the most important symptoms in asthma. The decreased PDEs  mRNA  and  inhibited cAMP-PDE  activities by BCG  contribute,  at least in part, prevention of allergen-induced airway inflammation and asthma in rats. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/312 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/312/312

Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 10 3 2011 09 15 221 226 EN Monireh Mokhtari Amirmajdi Department of Medical Mycoparasitology, Mashhad University of Medical Sciences, Mashhad, Iran Nemat Allah Mokhtari Amirmajdi Department of Otolaryngology, Ghaem Hospital, Mashhad University of Medical Sciences, Mashhad, Iran Iman Eftekharzadeh Mashhadi Department of Medical Mycoparasitology, Mashhad University of Medical Sciences, Mashhad, Iran Farahzad Jabari Azad Bu Ali Immunology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran Jalil Tavakol Afshari Bu Ali Immunology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran Mohammad-Taghi Shakeri Department of Biostatic, Mashhad University of Medical Sciences, Mashhad, Iran 2015 10 01 Inhalation of fungal spores is shown to participate in the development of allergic rhinitis symptoms. In this study, relation between presence of Alternaria in the human nasal cavity and allergic rhinitis is assessed. In a case-control study, 58 allergic rhinitis patients were compared with a well-matched control group of fifty healthy volunteers for sensitization to Alternaria (by skin prick test) and detection of Alternaria in their nasal mucous by conventional methods (microscopy with Methylene Blue stain and culture in Sabourad dextrose agar). Severity of the disease was determined according to  the ARIA classification. Pearson chi-square test was applied to compare the proportional difference between the study groups for detection of Alternaria in the nasal cavity, and sensitization to Alternaria. Relation between detection of Alternaria and allergic rhinitis was significant [OR = 18.18 (4.02-82.50)] In addition, sensitization to Alternaria showed a significant relation with the disease [OR  =  2.8 (2.1-3.8)]. There  was a significant relation between the  presence  of Alternaria in the nasal cavity and sensitization to Alternaria [OR =  10.4 (3.8-28.3)]. Both sensitization to  Alternaria and presence of Alternaria in the nasal cavity did not  have a significant relation with the severity of allergic rhinitis. This study suggests Alternaria as a major  allergen that  its  presence  in  the  nasal  cavity and  subsequent  development  of sensitization have significant role in the induction of allergic rhinitis. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/313 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/313/313

Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 10 3 2011 09 15 227 230 EN Zahra Alizadeh Immunology, Asthma & Allergy Research Institute, Tehran University of Medical Sciences, Tehran, Iran Mohammad Reza Fazlollahi Immunology, Asthma & Allergy Research Institute, Tehran University of Medical Sciences, Tehran, Iran Payman Eshghi Department of Pediatrics Department, Mofid Children Hospital, Shaheed Beheshti Medical University, Tehran, Iran Amir Ali Hamidieh Hematology-Oncology & SCT Research Centre, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran Zahra Pourpak Immunology, Asthma & Allergy Research Institute, Tehran University of Medical Sciences, Tehran, Iran Mohsen Ghadami Immunology, Asthma & Allergy Research Institute, Tehran University of Medical Sciences, Tehran, Iran 2015 10 01 Severe congenital neutropenia (SCN) is a rare primary immunodeficiency. Different genes are found to be associated with SCN, including ELA2, HAX1, WAS, GFI1, G-CSFR. Also, recently G6PC3 as a rare gene in SCN has been reported. Patients with G6PC3 often have cardiac and/or urogenital malformations. Two patients with   persistent   severe   neutropenia,   recurrent   infections   and   maturation   arrest   at promyelocyte-myelocyte stage in their bone marrow were assessed in this study. Both patients showed structural heart disease and one of them also showed urogenital anomaly. Sequence analyses of G6PC3 in 2 patients revealed two different homozygous mutations, one in exon 6 (Asn 313 fs), and the other in exon 3 (Ser 139 Met), the latter is a new mutation which has not been reported in previous studies. It  can be concluded that  G6PC3  is one of the responsible gene for SCN in Iranian patients. Based on the results, a new mutation in G6PC3 observed in one patient. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/314 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/314/314