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COVID-19, caused by SARS-CoV-2, requires new approaches to control the disease. Programmed cell death protein (PD-1) and cytotoxic T-lymphocyte–associated protein 4 (CTLA4) play important roles in T-cell exhaustion in severe COVID-19. This study evaluated the frequency of whole blood lymphocytes expressing PD-1 and CTLA-4 in COVID-19 patients upon admission to the intensive care unit (ICU) (i.e., severe) or infection ward (i.e., moderate) and after 7 days of antiviral therapy. COVID-19 patients were treated with either favipiravir or Kaletra (FK group, 11 severe and 11 moderate) or dexamethasone plus remdesivir (DR group, 7 severe and 10 moderate) for 7 days in a pilot study. Eight healthy control subjects were also enrolled. The frequency of PD-1 + and CTLA4 + lymphocytes in whole blood was evaluated by flow cytometry. Patients on DR therapy had shorter hospital stays than those on FK therapy. The frequency of PD-1 + lymphocytes in the FK group at baseline differed between COVID-19 patients and healthy controls, while the frequency of both PD-1 + and CTLA-4 + cells increased significantly 7 days of FK therapy. The response was similar in both moderate and severe patients. In contrast, the frequency of PD-1 + and CTLA-4 + lymphocytes varied significantly between patients and healthy controls before DR treatment. DR therapy enhanced PD-1 + but not the CTLA-4 + frequency of these cells after 7 days. We show that the frequency of PD-1 and CTAL-4-bearing lymphocytes during hospitalization was increased in Iranian ICU COVID-19 patients who received FK treatment, but that the frequency of CTLA-4 + cells was higher at baseline and did not increase in patients who received DR. The effectiveness of DR treatment may reflect differences in T-cell activation or exhaustion status, particularly in CTLA-4-expressing cells. [ABSTRACT FROM AUTHOR]

The cytokine storm and lymphopenia are reported in coronavirus disease 2019 (COVID-19). Myeloid-derived suppressive cells (MDSCs) exist in two different forms, granulocyte (G-MDSCs) and monocytic (M-MDSCs), that both suppress T-cell function. In COVID-19, the role of chemokines such as interleukin (IL)-8 in recruiting MDSCs is unclear. A recent report has correlated IL-8 and MDSCs with poor clinical outcomes in melanoma patients. In the current study, we evaluated the frequency of MDSCs and their correlation with serum IL-8 levels in severe COVID-19 patients from Iran. Thirty-seven severe patients (8 on ventilation, 29 without ventilation), thirteen moderate COVID-19 patients, and eight healthy subjects participated in this study between 10th April 2020 and 9th March 2021. Clinical and biochemical features, serum, and whole blood were obtained. CD14, CD15, CD11b, and HLA-DR expression on MDSCs was measured by flow cytometry. COVID-19 patients compared to healthy subjects had a greater frequency of M-MDSCs (12.7±13.3% vs 0.19±0.20%,), G-MDSCs (15.8±12.6% vs 0.35±0.40%,) and total-MDSCs (27.5±17.3% vs 0.55±0.41%,). M-MDSC (16.8±15.8% vs 5.4±4.8%,) and total-MDSC (33.3±18.5% vs 17.3±13.3%) frequency was higher in non- ventilated compared to moderate COVID-19 subjects. Serum IL-8 levels were higher in patients with COVID-19 than in normal healthy subjects (6.4±7.8 vs. 0.10±00 pg/mL). Ventilated patients (15.7±6.7 pg/mL), non-ventilated patients (5.7±2.7 pg/mL) and moderate patients (2.8±3.0 pg/mL) had significantly different levels of IL-8.  A negative correlation was found between the frequency of G-MDSCs and the international normalized ratio (INR) test (r=-0.39), and between the frequency of total-MDSCs and oxygen saturation (%) (r=-0.39). COVID-19 patients with severe non-ventilated disease had the highest levels of M-MDSCs. In addition to systemic MDSCs, lung, serum IL-8, and other inflammatory biomarkers should be measured. [ABSTRACT FROM AUTHOR]

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Tuberculosis (TB) remains a major threat to human health. Understanding the strategies mycobacteria take to overcome immune defense is important in order to control the infection. Micro (mi)RNAs are master regulators of most pathways in the human body.  Infection with mycobacterium impacts upon the host metabolic pathways as they are subverted to obtain the nutrition for intracellular TB survival. In this study, we aimed to investigate the effect of Bacillus Calmette-Guérin (BCG) infection on the expression of three miRNAs (miR-1224, -484 and -425), which are important in infection and in the regulation of metabolic pathways. Peripheral blood monocyte-derived macrophage (MDM) cultures were prepared and infected with BCG at a multiplicity of infection (MOI)=10 or left uninfected as a control. 72h post-infection, RNA was extracted from the cultured cells and cDNA synthesis and real-time PCR performed. Expression levels miRNAs were normalized to the levels of U6 snRNA (Rnu6) using the 2-ΔΔCt method. Infection with BCG resulted in a highly significant increase in miR-1224 expression (24.4±3.8-fold induction) in human MDMs. The induction of miR-484 (1.8±0.3-fold increase) and of miR-425 (1.2±0.2-fold increase) was less increased compared to miR-1224. Mycobacterium tolerates a hostile microenvironment by escaping from lysosomal degradation and providing a lipid-rich niche by trigger with and re-pattering host metabolism. This study highlighted the potential roles of miRNAs in host responses upon mycobacterium infection. [ABSTRACT FROM AUTHOR]

Nontuberculous mycobacteria (NTM) are categorized as one of the large and diverse groups of environmental organisms which are abundant in water and soil.  NTM cause a variety of diseases in humans that mainly affect the lung. A predisposition to pulmonary NTM is evident in patients with parenchymal structural diseases including bronchiectasis, emphysema, tuberculosis (TB), cystic fibrosis (CF), rheumatologic lung diseases and other chronic diseases with pulmonary manifestations. Lung infections are not the only consequences of being infected by NTM as they can also infect skin and soft tissue and may also cause lymphadenitis (predominantly in young children) and disseminated disease in human immunodeficiency virus (HIV)-infected patients or those with severely compromised immune system. NTM are also found in many subjects without any known risk factors.  Although the recent advances in imaging and microbiologic techniques including gene sequencing have provided a better view of the problems caused by NTM and has enhanced our understanding of the disease, many uncertainties regarding the immunologic response to NTM still exist. There is also limited data on the immunogenetics of NTM infection. Here, the authors reviewed the main immunogenetic defects as well as other immunological conditions which are associated with an increased the risk of NTM infections. [ABSTRACT FROM AUTHOR]

Inflammation is an important component of numerous cancers and chronic diseases and many inflammatory mediators have been shown to have potential prognostic roles. Tumor-infiltrating mast cells can promote tumor growth and angiogenesis, but the mechanism of mast cell activation is unclear. Early studies have shown that immunoglobulin free light chains (FLC) can trigger mast cell activation in an antigen-specific manner. Increased expression of FLC is observed within the stroma of many human cancers including those of breast, colon, lung, pancreas, kidney, and skin. These overexpressed FLCs are co-localized to areas of mast cell infiltration. Importantly, FLC expression is associated with basal-like cancers with an aggressive phenotype. Moreover, FLC is expressed in areas of inflammatory cell infiltration and its expression is significantly associated with poor clinical outcome. In addition, serum and bronchoalveolar fluid FLC concentrations are increased in patients with idiopathic pulmonary fibrosis (IPF) and hypersensitivity pneumonitis (HP) compared to control subjects. In this review, we provide an update on the role of FLC in the pathogenesis of several lung disorders and indicate how this may contribute to new therapeutic opportunities. [ABSTRACT FROM AUTHOR]

Asthma is a complex, heterogeneous and chronic airway inflammatory disease with different clinical phenotypes caused by diverse triggers and pathophysiological mechanisms. Asthma heritability has been established in many genetic studies but it is evident that only genetic elements are not responsible for the development of asthma. Increasing rate of asthma incidence during past decades has implicated the role of epigenetics in development of asthma. Environmental factors perform as initiator signals through epigenetic mechanisms. Three epigenetic mechanisms have been identified, including DNA methylation, histone modifications, and small noncoding RNAs. These mechanisms regulate the immune responses and inflammatory genes expression in asthma and allergy. This review explains the role of epigenetic modifications in controlling Th2 response and IgE production in asthma and also briefly overviews the role of environmental factors such as pollutions, allergens, prenatal exposures and diet in developing asthma. Recognizing environmental risk factors and their effects on epigenetic mechanisms would be of great interest for prognostic and preventive aspect in treatment of asthma. [ABSTRACT FROM AUTHOR]

Inflammatory responses and innate immunologic reactions play an important role in the respiratory system. Ex vivo lung perfusion (EVLP) is considered a novel method in the evaluation and reconditioning of donor lungs prior to transplantation. However, EVLP's effect on inflammatory and metabolic markers of human lung tissue is unknown.  This study investigated how the performance of EVLP on brain-dead (BD) donor lungs affects the production and release of inflammatory cytokines (IL-6, IL-8, and TNF-a), inflammatory cells and toll-like receptors (TLR) -2, 4. This study was conducted with an animal subject for qualification of EVLP team and then EVLP was performed on 4 human cases referred to Masih Daneshvari Hospital (Tehran,Iran), from May 2013 to July 2015. Two of these cases, who had acceptable lung function parameters, were enrolled in this study for immunologic investigations. Bronchoalveolar lavages (BAL) were taken before and after EVLP. Cytokines were quantitatively measured before lung retrieval, at the end of the lung removal, at the start of EVLP, and at the end of the each hour of EVLP. TLR expression was measured on the cells obtained by flow cytometry. TNF-a, IL-6 and IL-8 decreased in each stage of washing perfusate in both cases, and the level of cytokines in serum was in the normal range. Flow cytometry analysis revealed a decreasing expression of CD3, CD4/8, CD19, and CD16+56, as well as TLR-2 and TLR-4 in both cases. Intra-capillary pools of pro-inflammatory cytokines (IL-6, IL-8, and TNF-a) were determined to contribute to the lung injury during prolonged lung perfusion. This raises the possibility that EVLP donor lungs could be less immunogenic than standard lungs. However, to assess EVLP's effects on lung grafts and optimize recipient outcomes, further studies with a sufficient number of lungs are required. [ABSTRACT FROM AUTHOR]

Sarcoidosis is a systemic granulomatous disorder of unidentified etiology, with a heterogeneous clinical presentation. It is characterized by a reduced delayed-type hypersensitivity to tuberculin and common antigens. The balance between Th1, Th17 and Regulatory T(Treg) cells controls T-cell proliferation and activation.The Th17/Treg ratio in the peripheral blood and bronchoalveolar lavage fluidis increased in patients with active sarcoidosis. Amplified IL-17A expression in granulomas and the presence of IL-17A+, IL-17A+IL-4+ and IL-17A+IFN-γ+ memory T helper cells in the circulation and BAL indicate Th17 cell involvement in granuloma induction and/or maintenance in sarcoidosis. Sarcoidosis should therefore be considered as a Th1/Th17 multisystem disorder and anti-IL-17/Th17 approaches that control and reduce IL-17Amay be an option, therefore, for the treatment of sarcoidosis.Here we provide a short overview as to the role of Th17 cells as critical cells in the pathogenesis of sarcoidosis. [ABSTRACT FROM AUTHOR]

Tuberculosis (TB) and tobacco use are two major alarming global health issues posing immense threats to human populations. Mycobacterium tuberculosis (MTB) by activation of macrophages could induce the sequences of cells activation and releases of inflammatory cytokines such as CXCL-8, Il-12 and TNF-α which in turn induces the immune system network. However no information is available on other activity of cells by MTB and smoking. In the current study we aimed to investigate the serum levels TNF-a, CXCL-8 and phagocytosis capacity in tuberculosis patients with and without smoking. 103 subjects entered the study including 61 new diagnosed pulmonary TB patients (23 smokers and 38 nonsmokers) and 42 control healthy subjects. The phagocytosis of fluorescein isothiocyanate dextran (FITC-dextran) in blood monocytes/macrophages through flowcytometry was assessed. Serum levels of TNF-a and CXCL-8 were analyzed by ELISA methods. A lower percentage of cells from TB patients who smoked [50.29% (43.4-57.2), p<0.01] took up FITC-dextran after 2h compared to non-smoking TB subjects [71.62% (69.2-74.1)] and healthy cases [97.45% (95.9-99.1). Phagocytic capacity was inversely correlated with cigarette smoking as measured by pack years (r=-0.73, p<0.001). The serum levels of TNF-a and CXCL-8 were significantly higher in the TB patients who smoked compared to the TB non-smoker group (p<0.001, p<0.01 respectively). Blood monocytes/macrophages from TB patients have reduced phagocytic capacity which is further reduced in TB patients who smoke. Smoking enhanced serum levels of TNF-a and CXCL-8 suggesting a greater imbalance between the proinflammatory and anti-inflammatory factors in these patients. [ABSTRACT FROM AUTHOR]

The authors focus on epigenetic similarities between obstructive lung diseases (COPD), severe asthma, and treatment unresponsive sarcoidosis. They mention evidence suggesting that epigenetic mechanisms are involved in inflammation and immune cell function control in cancer and reflects on diseases associated with mesenchymal and epithelial cell remodeling within the alveoli and airways. They comment on the association of acetylated histone marks deposited by histone acetyltransferases with enhanced immune and inflammatory gene expression.

Innate lymphoid cells (ILCs) are identified as novel population of hematopoietic cells which protect the body by coordinating the innate immune response against a wide range of threats including infections, tissue damages and homeostatic disturbances. ILCs, particularly ILC2 cells, are found throughout the body including the brain. ILCs are morphologically similar to lymphocytes, express and release high levels of T-helper (Th)1, Th2 and Th17 cytokines but do not express classical cell-surface markers that are associated with other immune cell lineages. Three types of ILCs (ILC1, 2 & 3) have been reported depending upon the cytokines produced. ILC1 cells encompass natural killer (NK) cells and interferon (IFN)-g releasing cells; ILC2 cells release the Th2 cytokines, IL-5, IL-9 and IL-13 in response to IL-25 and IL-33; and ILC3 cells which release IL-17 and IL-22. ILC2 cells have been implicated inmucosal reactions occurring in animal models of allergic asthma and virus-induced lung disorders resulting in the regulation of airway remodeling and tissue homeostasis. There is evidence for increased ILC2 cell numbers in allergic responses in man but little is known about the role of ILCs in chronic obstructive pulmonary disease (COPD). Further understanding of the characteristics of ILCs such as their origin, location and phenotypes and function would help to clarify the role of these cells in the pathogenesis of various lung diseases. In this review we will focus on the role of ILC2 cells and consider their origin, function,location and possible role in the pathogenesis of the chronic inflammatory disorders such as asthma and COPD. [ABSTRACT FROM AUTHOR]

The immunopathology of sarcoidosis remains elusive despite years of research into this multiorgan disease.However, recent studies have provided new insights into the genetics and immune components involved in the clinical manifestation of the disease. Granulomatous inflammation is due to the host immune response to a persistent poorly degradable unknown antigen.Mycobacterium tuberculosis (MTB) is the major disease driver in many patients. The immune mechanisms that cause this disease start with the antigenic stimulus, followed by T-cell, macrophage and dendritic cell activation via a classic MHC II-mediated pathway. In addition, the profile of immune mediators reported in sarcoidosis indicates that the inflammasome pathway plays a critical role in disease pathogenesis. Increased understanding of the signal transductions pathways involved in the induction of inflammatory processes in sarcoidosis could give rise to new therapeutic approaches in future. [ABSTRACT FROM AUTHOR]

Objectives: Tetrameric Ig are produced and secreted by plasma cells, but they also produce and secrete Ig-free light chains (FLC κandυ). Studies in animal models of allergic disease suggest the existence of an IgE-independent hypersensitivity response involving antigen-induced mast cell activation mediated by FLCs. FLCs are increased during mucosal immune responses and are possibly involved in the pathogenesis of various atopic and non-atopic diseases. We aimed to explore the relation between serum FLC and IgE in patients with high levels of specific IgE for food and respiratory allergens. Material and Methods: 37 subjects with food allergy, 27 subjects with respiratory allergy and controls were selected and serum was collected for determination of κand υFLCs, total IgE by ELISA. Specific food and respiratory allergens were detected using Improvio C Blotting. Results: Serum FLCs were found significantly increased in respiratory and food allergic patients. In cow's milk allergic patients, no increase in specific IgE was detected, while serum FLCs were found increased. No correlation between FLC and total serum IgE was found. Conclusions: We show that FLCs are significantly augmented in patients with high total and allergen-specific IgE. No significant correlation between FLC and allergen-specific IgE was found indicating an IgE-independent production of FLCs. Interestingly; total FLC levels in cow's milk allergic subjects are raised even in the absence of elevated allergen-specific IgE, which suggests that detection of FLC may be a complementary biomarker for allergy. [ABSTRACT FROM AUTHOR]

Objective: Mendelian susceptibility to mycobacterial disease (MSMD) is a rare congenital disorder characterized by susceptibility to clinical disease caused by poorly virulent mycobacteria, such as Bacillus Calmette-Gu erin (BCG) or nontuberculous mycobacteria (NTM). Known genetic etiologies of MSMD affect the IL-12-interferon (IFN)-γ immunological circuit, with mutations in six genes. Furthermore, germline mutations in the (IFNGR1 IFNGR2 STAT1 IL12B, IL12RB1 and NEMO). CYBB and in the IRF8 have been recently identified as the genes, which are responsible for MSMD. The occurrence of MSMD in patients born to consanguineous parents and in siblings strongly suggested that most cases followed an autosomal recessive (AR) mode of inheritance. Functional and mutation analysis was evaluated in suspected patients to MSMD. Material and Methods: This study was performed on 23 cases at age 5-28 years old, which had mycobacterial Tuberculosis or NTM infections and suspected MSMD. Whole blood cell culture was performed in presence of rIFN-γ, rIL-12 and LPS for 24 and 48 h. The supernatants were assayed for IFN-γ, IL-12p40 by ELISA method. QF-T also has been done to all the patients. Flow cytometry for analysis of IFN-γsubunits has been conducted. Results: All patients presented with complications of BCG vaccine in the form of localized lymphadenitis or disseminated BCG infection and chronic osteomyelitis. In-vitro studies showed that 3 cases had impaired response to IL-12. The adult patients had partial defects in IL-12 signaling. One patient mostly at age 5-8 had defects in IFN-γ signaling. In all cases mutation assays for defect loop of IL-12 and IFN-γ has been examined. Conclusion: It is concluded that partial defects of IL-12/IFN-γloop demonstrated at adult rather than pediatrics and mutation analysis with functional assays in combination with flow cytometry could give precise diagnosis of MSMD. [ABSTRACT FROM AUTHOR]

Objective: Poly lactic-co-glycolic acid (PLGA), a biodegradable polymer, can effectively protect encapsulated peptides from enzymatic degradation. PLGA was approved by FDA as a safe drug delivery system suitable for inhalation administration. Vasoactive intestinal peptide (VIP), a 28-amino-acid peptide, displays anti-inflammatory and anti-spasmodic effects, which can be considered as a new therapeutic option to control and treat asthma. Because of in vivo enzymatic degradation of VIP including in the lung, there is a need for an applicable delivery system. Material and Methods: In light of this, the purpose of this study was to prepare VIP-loaded PLGA microspheres as a drug delivery system, assuming that the newly-introduced model has the ability to persist for a longer time in respiratory tracts. The PLGA microsphere was produced, and loaded with VIP as an applicable nanodrug system. A series of physiochemical properties were determined, including the morphological characteristics, average size of nanoparticles, electric charge distribution, FTIR spectroscopy absorption, and loading and releasing percentage of the nanodrug. Results: VIP loaded PLGA exhibited an average size of approximately 550±50 nm. Additionally, the produced microsphere showed 78 % VIP release after 10 h at the pH value corresponding to bronchioalveolar microenvironment (approximately 6.5). Conclusion: In the present study, PLGA was formulated and used as a delivery system for VIP. Taken together, the newly introduced nanodrug seems to be helpful for the clinical treatment of allergic asthma. PLGA nanoparticles can be considered as a potential efficient delivery system for VIP in the respiratory system. [ABSTRACT FROM AUTHOR]

Different phenotypes of asthma from mild to severe are categorized based on diverse clinical features. A guideline for the recognition and treatment of asthma has been provided by Global Initiative for Asthma (GINA). To control symptoms and prevent asthma exacerbation in most patients combinational therapy with inhaled corticosteroids (ICS) and a long acting B2-adrenreceptor agonist (LABA) are recommended. Understanding asthma phenotypes would be helpful to improve asthma diagnosis and treatment. The aim of this study was to verify glucocorticoid receptor glcococorticoid receptor (GR) nuclear translocation in CD4 T cells treated with fluticasone furoate (FF), vilanterol (V) and FF/V combination in severe asthmatic patients compare to patients with moderate asthma and healthy controls using Immunocytochemistry (ICC). After taking blood and separating PBMCs from each subject, CD4 T cells were isolated from PBMCs using CD4+ T cell isolation kit. Isolated CD4 T cells were cultured in presence of FF, V and FF/V combination for 1 hour and after cytocentrifugation, cells were incubated with anti GR-antibody and subsequently stained with FITC bound secondary antibody and GR nuclear translocation was observed under microscope. The results showed significant increasing in GR nuclear translocation in treated CD4 T cells from patients with moderate asthma and controls compare to those severe asthmatic patients, along with treating cells with FF/V combination no significant GR nuclear translocation was observed compare to that of using mono treatment of cells with FF and V. Based on our findings, it can be concluded different mechanisms are responsible for severe asthma and moderate asthma. [ABSTRACT FROM AUTHOR]

Fibrosing pneumonia (FP) is classified into usual interstitial pneumonia (UIP) and nonspecific interstitial pneumonia (NSIP), each having its own etiology and prognosis. Both types of FP are progressive and chronic conditions with distinct etiologies. Cytokines and inflammatory mediators play critical roles in the pathogenesis of FP. Among them, the role of transforming growth factor beta-1 (TGF-β1) and modulators triggering fibrosis are not well understood. In this study, the expression of triggering receptor expressed on myeloid cells-1 (TREM-1) as a stimulator for the production of TGF-β1 and also CD4+CD25+Foxp3+ regulatory cells were investigted in FP patients. Sixteen UIP, 14 NSIP and 4 pulmonary fibrosis following Mycobacterium tuberculosis (TB) infection patients, were compared with 12 healthy controls. The frequency of blood CD14+TGF-β1+ and CD14+TREM1+-gated monocytes and CD4+CD25+Foxp3+ regulatory T cells (Treg), as well as the plasma levels of TGF-β1 and IL-10 were measured. Fibrosis patients compared to healthy controls had a greater frequency of CD14+TGF-β1+ [15.9 (0.2-88.2) vs. 0.6 (0.2-11.0)] and CD14+TREM1+ [21.1 (2.3-91.2) vs. 10.3 (3.1-28.6)]-gated monocytes, and CD4+CD25+Foxp3+ [1.2 (0.3-3.6) vs. 0.2 (0.1-0.4)]-gated lymphocytes. Plasma TGF-β1 were also significantly increased in patients with fibrosis compared to healthy controls [9316.2 (±5554.4) vs. 3787.5 (±2255.6)]. These results confirm the importance of TGF-β1 and TREM1 in pulmonary fibrosis. It seems that this reciprocal cycle in healthy people is modulated by the production of IL-10 by Treg cells, thus limiting fibrosis, as observed in patients following TB infection. Further investigations are recommended to evaluate possible immunomodulatory mechanisms defects in pulmonary fibrosis. [ABSTRACT FROM AUTHOR]

Cystic fibrosis (CF) is the most common lethal autosomal recessive disease in white Caucasians. It affects many organs including the lung, pancreas, and liver. Whilst CF is a monogenic disease, several studies revealed a complex relationship between genotype and clinical phenotype of diseases. We examined the expression of human leukocyte antigen (HLA) class II alleles among Iranian CF patients with disease-related microbial infection. This study was conducted on 50 hospitalized CF patients (27 males, 23 females aged 15.5±6.5 years), and 50 healthy age- and gender-matched control subjects. 5ml whole blood was harvested and after isolation of genomic DNA, HLA-DRB1 subtypes were determined by single specific primer polymerase chain reaction methods. HLA-DRB1*10 was less frequent and HLA-DRB1*04 and HLA-DRB1*11 was the most frequent allele in CF patients, but none reached significance. HLA-DRB1*04 allele was frequently seen among16 CF patients with high serum IgE levels (430.25±219.7 IU/mL) and 27 CF patients that were positive for Pseudomonas aeruginosa colonization. A total of 31 CF patients had candida Albicans colonization in whom HLA-DRB1*11 was mostly seen. A total of 3 CF patients had allergic bronchopulmonary aspergillosis and two were diabetic. The DR4 and DR11 serotypes that recognize the HLA-DRB1*04 and HLA-DRB1*11 gene products respectively are not significantly enriched in the Iranian CF population. Further research should be conducted on DR4 and DR11 in CF patients to understand their possible role in infection and IgE expression. [ABSTRACT FROM AUTHOR]

In this study, we first tried to determine whether the expression level of 9 miRNAs in the peripheral blood CD8+ T cells of asthmatic patients varies from that of controls, and secondly, we investigated the effects of fluticasone furoate and vilanterol on the expression level of these miRNAs. Fifteen subjects including 8 healthy individuals and 7 asthmatic patients were included in this study. CD8+T cells were isolated from participants' peripheral blood by a negative selection method using magnetic-activated cell sorting (MACS). The expression of 9 miRNAs was examined between the healthy individuals and asthmatic patients. Then the expression level of 9 miRNAs before and after treatment with the drugs was examined by quantitative real-time PCR. No significant changes in the expression level of 9 miRNAs were observed in asthmatic patients compared to the healthy controls. Fluticasone and vilanterol, in combination, had the greatest effect on miRNA expression. MiR-150 and miR-106a were the most and the least miRNAs, respectively, present in CD8+ T cells of patients and controls. MiR-106a and miR-126 had a positive correlation in CD8+ cells of asthmatic patients. Although no significant difference in the expression level of studies miRNAs was observed, the correlations among miRNAs were significant. Therefore, we suggest that the correlation between miRNAs would be a very important factor in physiological and pathological conditions in healthy individuals and asthmatic patients. Such a miRNA-miRNA correlation network can be even more critical than any changes in the variation of their expression in the CD8+ T cells. [ABSTRACT FROM AUTHOR]

Objective: Mast cells are connective tissue cells that mostly known for their role in allergic and other inflammatory disease. They play important role in immediate allergic reactions and inflammatory responses. There are evidences illustrating the involvement of these cells in other numerous physiological and pathophysiological reactions. The aim of the present study was to establish a simple and affordable method for the differentiation and culture of murine mast cells from rat bone marrow. Materials and Methods: Mast cells were generated from bone marrow of 10-15 weeked aged male mice based on a modified method change of the tissue culture flasks from 75-cm2 to 25-cm2 via supernatant of the spleen cell culture medium. The granularity of the mast cells was determined using toluidine blue staining. Mast cells were characterized and analyzed using Mast Cell Tryptase Antibody and CD 117, CD 34. Tryptase activity was present only in mast cell. It is helpful method to distinguish the activation of mast cell from other cells as neutrophils. Results: Mast cells were generated from bone marrow of male rat. The cells were positive for Mast cell-related antigens for each of CD117 and Tryptase, and negative for CD34. Conclusions: In the present study change of the tissue culture flasks from 75-cm2 to 25-cm2 ended up more dense arrangement of the cells and subsequently the effect of the secreting factors like IL4, IL3 and SCF was enhanced and improved. [ABSTRACT FROM AUTHOR]

The underlying mechanisms of how nicotine affects cord umbilical cells remain largely elusive. Nicotine rapidly crosses the blood-brain barrier (10 to 20 s) and binds to nicotinic acetylcholine receptors (nAChRs). Nicotine considered as a major compound found in cigarette smoke and the mechanism of nicotine action in immune response is not well understood. Cigarette smoke well known by activation of toll like receptors (TLRs) especially TLR4 and 9 which stimulates the immune response by induction of releases of cytokines mainly CXCL-8 which in turn triggers lungs reactions specially induction of neutrophils recruitments. In this study we isolated human umbilical mononuclear cells (UCBMC) from umbilical cord blood and exposed to the nicotine for detection any cytokines and TLRs modulation. We have found that nicotine (at concentration 0.01μM) induced release of TNF-α and IL-6 but not CXCL-8 production. Besides we have shown that nicotine did not effect on TLR4 surface expression however up-regulated the TLR2 surface expression. Moreover expression of CD11a and CXCR4 after nicotine incubation was upregulated as demonstrated by flow cytometry analysis, These data indicated that nicotine by stimulation of inflammatory cytokines induces immune response. The present study provides evidence that nicotine selectively regulates the release of cytokines and expression of TLRs. Further studies are needed to exploring details of its effects and signaling. [ABSTRACT FROM AUTHOR]

Objective: Asthma is a chronic respiratory disease characterized by airway inflammation, bronchoconstriction, airway hyperresponsiveness and recurring attacks of impaired breathing. Vasoactive intestinal peptide (VIP) has been proposed as a novel anti-asthma drug due to its effects on airway smooth muscle relaxation, bronchodilation and vasodilation along with its immunomodulatory and anti-inflammatory properties. Material and Methods: In the current study, we investigated the therapeutic effects of VIP when conjugated with α-alumina nanoparticle (α-AN) to prevent enzymatic degradation of VIP in the respiratory tract. VIP was conjugated with α- AN. Balb/c mice were sensitized and challenges with ovalbumin (OVA) or PBS and were divided in four groups; VIP-treated, α-ANtreated, α-AN-VIP-treated and beclomethasone-treated as a positive control group. Specific and total IgE level, airway hyperresponsiveness (AHR), bronchial cytokine expression, and lung histology were measured. Results: α-ANVIP significantly reduced the number of eosinophil (Eos), serum IgE level, Th2 cytokines and AHR. These effects of α-AN-VIP were more pronounced than that seen with beclomethasone or VIP alone (P<0.05). Conclusion: The current data indicate that α-AN-VIP can be considered as an effective nano-drug for the treatment of asthma. [ABSTRACT FROM AUTHOR]