Heting Dong; Yinying Ren; Yiyi Song; Wei Ji; Yongdong Yan; Canhong Zhu; Li Huang; Meijuan Wang; Wenjing Gu; Xinxing Zhang; Huiming Sun; Chuangli Hao; Zhengrong Chen
Abstract
Background: Neutrophilic asthma is characterized by the predominant infiltration of neutrophils in airway inflammation.Objective: To explore the therapeutic potential of an antibody against the inducible T cell co-stimulator ligand (ICOSL) in a mouse model of neutrophilic asthma.Methods: Female BALB/c ...
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Background: Neutrophilic asthma is characterized by the predominant infiltration of neutrophils in airway inflammation.Objective: To explore the therapeutic potential of an antibody against the inducible T cell co-stimulator ligand (ICOSL) in a mouse model of neutrophilic asthma.Methods: Female BALB/c mice were randomly assigned to different groups. They were then injected with ovalbumin (OVA)/lipopolysaccharides (LPS) to induce neutrophilic asthma. The mice were then treated with either anti-ICOSL (the I group), control IgG (the G group), or no treatment (the N group). Additionally, a control group of mice received vehicle PBS and was labeled as the C group (n=6 per group). One day after the last allergen exposure, cytokine levels were measured in plasma and bronchoalveolar lavage fluid (BALF) using ELISA. After analyzing and categorizing BALF cells, the lung tissues were examined histologically and immunohistochemically.Results: Administering anti-ICOSL resulted in a significant decrease in the total number of inflammatory infiltrates and neutrophils found in BALF. Moreover, it led to a decrease in the levels of interleukin (IL)-6, IL-13, and IL-17 in both BALF and plasma. Additionally, there was an increase in IFN-γ levels in the BALF of asthmatic mice (p<0.05 for all). Treatment with anti-ICOSL also reduced lung interstitial inflammation, mucus secretion, and ICOSL expression in asthmatic mice.Conclusion: The treatment of anti-ICOSL effectively improved lung interstitial inflammation and mucus secretion in mice with neutrophilic asthma by restoring the balance of Th1/Th2/Th17 responses. These findings indicate that blocking the ICOS/ICOSL signaling could be an effective way to manage neutrophilic asthma.
Shole Daneshvar-ghahfarokhi; Amir Rahnama; Vahid Mohammadi-Shahrokhi
Abstract
Background: One of the inflammatory diseases of the respiratory system is asthma. Teucrium polium (TP) has anti-inflammatory and anti-allergic properties and its anti-asthmatic effects have not been investigated yet. RORγt is an inflammatory transcription factor for Th17 differentiation. By secreting ...
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Background: One of the inflammatory diseases of the respiratory system is asthma. Teucrium polium (TP) has anti-inflammatory and anti-allergic properties and its anti-asthmatic effects have not been investigated yet. RORγt is an inflammatory transcription factor for Th17 differentiation. By secreting IL-17, Th17 leads to neutrophilic inflammation in the lungs. As an anti-inflammatory cytokine, IL-10 reduces the dissemination of inflammatory elements in the airways.Objective: To evaluate the effect of TP extract in asthma treatment.Methods: Thirty female Balb/c mice were distributed into 5 groups (n=6) including the control, treated with ovalbumin (OVA), and OVA+ various doses of TP (50, 150, and 300 mg/kg). All groups except the control group were sensitized to OVA solution on days 0, 7, and 14 by subcutaneous injection. The challenge was performed on days 18 to 21 by the inhalation of 1% OVA and the treatment was done with TP extract in the treatment groups, half an hour before the challenge. On day 22, the serum and spleen samples were collected to determine IL-10 serum levels and RORγt gene expression, respectively.Results: In the treatment groups, the expression of RORγt significantly decreased when using OVA+ Tp extract (150 mg/kg and 300 mg/kg), and IL-10 serum levels significantly increased when using OVA+ TP extract (150 mg/kg) compared with the OVA group.Conclusion: It is possible that TP extract can be effective in improving asthma by reducing inflammation.
Yien Yao; Xiaoju Chen; Caicheng Qin; Jianlin Huang; Siyue Xu; Chaoqian Li
Abstract
Background Dysregulation of the balance between different T cell populations is believed to be an important basis for asthma.Objective To observe the changes in γδT subtypes in transgenic asthmatic mice after aerosol inhalation of Mycobacterium vaccae, and to further investigate the mechanism ...
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Background Dysregulation of the balance between different T cell populations is believed to be an important basis for asthma.Objective To observe the changes in γδT subtypes in transgenic asthmatic mice after aerosol inhalation of Mycobacterium vaccae, and to further investigate the mechanism of M. vaccae in asthmatic mice and its relationship with γδT cells.Methods TCR-β-/- mice were exposed to atomized normal saline or M. vaccae for 5 days and the γδT cells from the lung tissues were isolated. Changes in γδT17 and γδTreg populations were detected. Asthma was induced in BALB/c mice using ovalbumin, which was then transplanted with control or M. vaccae-primed γδT cells. First we analyzed the content of γδT cells that secrete IL-17 (IL-17 γδT cells) and Foxp3+ γδT cells in lung tissues and then measured the content of IL-17 in the bronchoalveolar lavage fluid (BALF) by ELISA.Results Exposure to M. vaccae increased and decreased the relative proportions of Foxp3+ γδT cells and IL-17+ γδT cells, respectively, thereby decreasing airway reactivity and inflammation levels in asthmatic mice, and significantly decreasing IL-17 levels in BALF. Furthermore, mice treated with these primed T cells showed a decrease in IL-17+ γδT cells, and a concomitant increase in Foxp3+ γδT cells in their lung tissues. Furthermore, adoptive transfer of M. vaccae-primed γδT cells decreased GATA3 and NICD and increased T-bet in lung.Conclusions The M. vaccae-primed γδT cells alleviated the symptoms of asthma by reversing Th2 polarization in the lungs and inhibiting the Notch/GATA3 pathway.
Zhangqiao Cai; Xuxia He; Jing Yang
Abstract
Background: Allergic asthma is believed to be a T helper 2 cell (Th2) preponderant response caused by airway hyper-responsiveness. Interleukin-35 (IL-35) is a newly discovered anti-inflammatory cytokine. Objective: To determine whether the expression of IL-35 is associated with type-2 inflammation in ...
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Background: Allergic asthma is believed to be a T helper 2 cell (Th2) preponderant response caused by airway hyper-responsiveness. Interleukin-35 (IL-35) is a newly discovered anti-inflammatory cytokine. Objective: To determine whether the expression of IL-35 is associated with type-2 inflammation in children with asthma exacerbations. Methods: Thirty children (6-12 years old) with acute allergic asthma and twenty healthy controls were enrolled. Sputum was collected from lower airways. IL-35 and type 2 cytokines expression from serum and sputum were measured at mRNA and protein level by real-time PCR and enzyme-linked immunosorbent assay (ELISA), respectively. The sampling and the test were repeated eight weeks after the asthma exacerbation. Results: At the time of exacerbation, IL-35 expression decreased significantly in induced sputum and serum than in the controls. The expression of IL-35 was negatively correlated with IL-4, IL-5 and IL-13 expression. The IL-35 from induced sputum increased significantly, whereas type-2 cytokines decreased significantly eight weeks after the exacerbation. Conclusion: Our results showed that decreased IL-35 was associated with type-2 cytokines in asthma exacerbations in children, suggesting that IL-35 may be a potential future drug target for asthma exacerbations.
Soheila Alyasin; Reza Amin; Ali Fazel; Mohammad Hossein Karimi; Seyed Hesamedin Nabavizadeh; Hossein Esmaeilzadeh; Maryam Babaei
Volume 14, Issue 1 , March 2017, , Pages 73-80
Abstract
Background: Asthma is the chronic inflammation of airways characterized by eosinophilic infiltration, mucus overproduction, airway hyper-responsiveness and airway remodeling. These changes are induced mostly by cytokines which are produced by T helper (Th) 2 cells. Recently, the role of interleukin-23 ...
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Background: Asthma is the chronic inflammation of airways characterized by eosinophilic infiltration, mucus overproduction, airway hyper-responsiveness and airway remodeling. These changes are induced mostly by cytokines which are produced by T helper (Th) 2 cells. Recently, the role of interleukin-23 (IL-23) in the pathogenesis of adultallergic asthma has been studied. Objective: To explore IL-23 serum levels and its expression in persistent asthma compared with healthy children younger than five years old. Method: Blood samples of 40 children with mild and severe persistent asthma were compared to 34 healthy children regarding IL-23 serum levels and gene expression using enzyme-linked immunosorbentassay (ELISA) and real time quantitative polymerase chain reaction (PCR). Results: The IL-23 gene expression level was significantly different in the 25 children with mild persistent asthma and the 15 children with severe persistent asthma compared to the control group (p=0.001).There was no significant difference in IL-23 gene expression level between the two groups of patients with mild and severe persistent asthma. A significant difference was seen in IL-23 serum levels between the 25 children with persistent asthma and control group (p=0.002).Conclusion: For pre-school children with history and physical exam in favor of asthma which cannot be tested by spirometry, IL-23 serum levels may be an auxiliary biomarker for the diagnosis of asthma.
Magdy Mohamed Zedan; Amal Mohamed Osman; Wafaa Nabil Laimon; Mohamed Magdy Zedan; Nermin Youssef Abo-elkheir; Ahmed Zaki
Volume 13, Issue 2 , June 2016, , Pages 70-88
Abstract
Asthma is a heterogeneous disease, in which asthmatic patients present with different clinical phenotypes, variable endotypes, and different response to asthma medicines. Thus, we are faced with an asthma paradox; asthma is diagnosed subjectively by clinical history and treated with biologically active ...
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Asthma is a heterogeneous disease, in which asthmatic patients present with different clinical phenotypes, variable endotypes, and different response to asthma medicines. Thus, we are faced with an asthma paradox; asthma is diagnosed subjectively by clinical history and treated with biologically active drugs. To solve this paradox, we need objective airway biomarkers to tailor the proper medications to the proper patient. Biomarkers should have one or more of the following characteristics: 1) could differentiate poor symptoms perceivers from over-perceivers, 2) could predict disease activity and hence disease outcome, 3) could clarify asthma phenotype responders from non-responders, and finally 4) could characterize different clinical asthma phenotypes. Therefore, we have conducted a review of literature trying to apply those four parameters to different airway inflammatory biomarkers. We found that FeNO fulfilled the four proposed clinical parameters of airway inflammatory biomarkers whereas; serum periostin was the single best systemic biomarker of airway luminal and tissue eosinophilia in severe uncontrolled TH2 asthma phenotype. Thus, this may be considered a trial towards tailoring the proper medication to the proper patient. However, application of biomarkers in clinical practice requires easier and cheaper techniques together with standardized methods for sample collection and analysis.
Masooma Abdullahi; Reza Ranjbaran; Soheaila Alyasin; Zeinab Keshavarz; Amin Ramezani; Abbas Behzad-Behbahani; Sedigheh Sharifzadeh
Volume 13, Issue 1 , March 2016, , Pages 27-36
Abstract
Background: Asthma is very common in children and its diagnosis is based on clinical manifestations, which can be misdiagnosed as other respiratory diseases with similar signs and symptoms. Objective: To analyze the expression of ST2L and CD203c in the diagnosis of pediatric asthma. Methods: Basophils ...
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Background: Asthma is very common in children and its diagnosis is based on clinical manifestations, which can be misdiagnosed as other respiratory diseases with similar signs and symptoms. Objective: To analyze the expression of ST2L and CD203c in the diagnosis of pediatric asthma. Methods: Basophils were purified from whole blood samples of patients and healthy controls using Ficol-Paque gradient and Basophil Isolation Kit. RNA extraction was done by RNX-Plus solution and after synthesis of cDNA, the gene expression was analyzed by means of real time PCR. Results: Patients expressed significantly higher levels of CD203c than healthy controls (p=0.01). Although there was an increase in the transcription level of ST2L gene in patients, the results were not statistically significant compared to those obtained from the healthy controls (p>0.05). A Specificity of 60% and a sensitivity of 73% were foundusing ROC curve for CD203c expression. Patients with positive family history of asthma exhibited more CD203c and ST2L expression (p<0.05). Conclusion: It is proposed that determining CD203c expression by real time PCR may be an effective technique for diagnosis of pediatric asthma.
Mahendra Narain Mishra; Puja Dudeja; Rakesh Kumar Gupta
Volume 11, Issue 1 , March 2014, , Pages 21-28
Abstract
Background: Pediatric bronchial asthma is associated with considerable morbidity. The study was carried out to examine the association of Human Leukocyte Antigen (HLA)- Class II with the disease as we found no similar study on Asian Indian population. Objective: To define the HLA-Class II antigens in ...
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Background: Pediatric bronchial asthma is associated with considerable morbidity. The study was carried out to examine the association of Human Leukocyte Antigen (HLA)- Class II with the disease as we found no similar study on Asian Indian population. Objective: To define the HLA-Class II antigens in Asian Indian pediatric patients with asthma. Methods: A total of 103 children with asthma and 152 controls were analysed for HLA Class II (DRB1, DQB1and DPB1) by PCR-SSP (Sequence Specific Primers) method. Total serum IgE levels were determined by ELISA assay. Results: A positive family history was recorded in 59 patients (57%) and 13 (8.5%) of healthy controls. Serum IgE levels were more than normal range in 72% of the patients and 33% of healthy subjects with mean values of 4877 and 627 IU/ml, respectively. DRB1*04 and DQB1*03 showed significant positive relations while DRB1*15 showed a negative association with asthma. DQB1*02 was more common in healthy individuals but was not statistically significant. Conclusions: A positive association of the DR4/DQB1*03 and a negative association of DRB1*15 was seen with extrinsic bronchial asthma. However, more studies are required on larger populations to confirm the association of HLA Class II alleles in Indians before a particular allele can be labeled as being protective or causative for asthma.
Javad Ghaffari; Mohammad KHademloo; Mohammadjafar Saffar; Alireza Rafiei; Farzad Masiha
Volume 7, Issue 4 , December 2010, , Pages 234-239
Abstract
Background: Asthma and allergic rhinitis are among the most common diseases in the world. Objective: The aim of this study was to detect, by skin prick test, aeroallergens in allergic patients in Sari, Mazandaran in north of Iran. Methods: This is a prospective study of skin prick test of aeroallergens ...
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Background: Asthma and allergic rhinitis are among the most common diseases in the world. Objective: The aim of this study was to detect, by skin prick test, aeroallergens in allergic patients in Sari, Mazandaran in north of Iran. Methods: This is a prospective study of skin prick test of aeroallergens in asthma, allergic rhinitis and their combination with clinical diagnosis. Three hundred and seventy five cases aged between 5 to 50 years, were referred to Tooba and Boo-Ali allergic centers of Mazandaran University of Medical Sciences between December 2006 and July 2009. The aeroallergens studied included house dust mites (Dermatophagoides farinae, Dermatophagoides pteronyssinus), cockroaches, feather, aspergillus, Alternaria, pigweed, nettle, oak and maple. Results: Of the studied individuals, 175 cases were males (46.7%) and 200 were females (53.3%), of which 156 (n=41.5%) reacted to allergen extracts. In asthma, allergic rhinitis and their combination, the respective positive percentages were 26.6%, 22.9%, and 32.6% for Dermatophagoides farinae; 26.6%, 25.3%, and 23.3% for Dermatophagoides pteronyssinus; 12.7%, 17.4%, and 11.6% for cockroaches and 16.5%, 4.7%, and 7.0% for the feather. Other allergens were positive up to 5 percent. Total IgE levels were elevated in 56.4%, 53% and 60.5% of asthmatic, allergic rhinitis and the combination group, respectively. Eosinophils count was elevated in 40.5%, 33.2% and 37.2% of the same groups, respectively. Conclusion: The hypersensitivity to house dust mites is very common in north of Iran which may be attributed to the warm and humid weather of this area.
Tahereh Mousavi; Alireza Salek Moghadam; Reza Falak
Volume 5, Issue 1 , March 2008, , Pages 57-63
Abstract
Background: There are many therapeutic methods for allergic conditions. CpG oli-gonucleotides play a critical role in immunity via the augmentation of Th1 and suppres-sion of Th2 responses. Objective: In the present study we aimed to estimate the effec-tiveness of intranasal administration of CpG ODN ...
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Background: There are many therapeutic methods for allergic conditions. CpG oli-gonucleotides play a critical role in immunity via the augmentation of Th1 and suppres-sion of Th2 responses. Objective: In the present study we aimed to estimate the effec-tiveness of intranasal administration of CpG ODN plus Chenopodium album allergen in allergic asthma compared with the administration of allergen alone and to find out how CpG ODN therapy is useful in the treatment of allergen induced asthma. Methods: BALB/c Mice were intraperitoneally and intranasally sensitized with allergenic extract precipitated on aluminum hydroxide. Therapy with CpG/Ag was performed intrana-sally. After antigenic challenge, a number of Immunologic variables such as serum IgE and IgG, systemic and local IL-10 and IFN-γ were studied in splenocytes, and lung tis-sue culture supernatants, respectively. Results: Our study indicated that intranasal ad-ministration of CpG/Ag had significant increases in both systemic and local levels of IL-10 and IFN-γ (p≤ 0.001), but showed no significant effect on the levels of IgE, IgG2a, and IgG1 in serum (p= 0.06). This study demonstrated that CpG ODN has thera-peutic effects not only on splenocytes but also on nasal lymphocytes to produce IFN-γ as a Th1 cytokine, and IL-10 as a regulatory cytokine. Conclusion: According to these data from the mouse model, we conclude that intranasal administration of CpG motifs before allergen exposure may be useful for the control of allergic asthma. Therefore, further investigations on humans using CpG motifs are recommended in order to modu-late the allergic effects of Chenopodium album as well as other regional allergens.
Alireza Salek Moghaddam; Mohammad Shabani; Farahdokht Fateminasab; Mohammad Reza Khakzad
Volume 2, Issue 2 , June 2005, , Pages 103-110
Abstract
Background: Asthma is a chronic inflammatory disease with multifactorial and complicated mechanisms. Elevated level of exhaled Nitric Oxide (NO) in asthma and other inflammatory lung diseases has led to many studies examining NO as a potential marker of airway inflammation. Objective: This study was ...
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Background: Asthma is a chronic inflammatory disease with multifactorial and complicated mechanisms. Elevated level of exhaled Nitric Oxide (NO) in asthma and other inflammatory lung diseases has led to many studies examining NO as a potential marker of airway inflammation. Objective: This study was designed to determine the level of NO in Bronchoalveolar Lavage (BAL) fluid during early and late stages of asthmatic attack in mouse model. Methods: In this study male BALB/c mice were used. The level of NO was determined in BAL fluid of asthmatic mice five minutes, six and sixteen hours after challenge with methacholine, as irritant and smoke and 5% ovalbumin as allergens, using colorimetric assay. Results: The level of NO increased upon exposure to all three irritants used in this study (52.3 μM for smoke and 49.5 μ Mfor methacholine) as compared to 22.8 μM for the baseline. Our results showed that NO levels were increased during early phase of asthmatic condition and reached to its maximum level after six hours and decreased at the late stage of asthma (16hrs) possibly by activating a feedback regulatory loop. In addition, high level of NO led to the hypertrophy of smooth muscle that can account for the pathological changes associated with asthma. Conclusion: Thus, NO is an inflammatory marker in asthma and its measurement, as a non-invasive method during asthmatic attack is suggested. A careful development of specific inhibitors for iNOS enzyme during asthmatic attack is also necessary.
