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1.
Laurie S Davis Sumit Bhutani Sherry Ridz Barnett David A Khan 《Clinical and molecular allergy : CMA》2011,9(1):1-10
Background
Allergic rhinitis (AR) affects up to 80% of children with asthma and increases asthma severity. Thymic stromal lymphopoietin (TSLP) is a key mediator of allergic inflammation. The role of the TSLP gene (TSLP) in the pathogenesis of AR has not been studied.Objective
To test for associations between variants in TSLP, TSLP -related genes, and AR in children with asthma.Methods
We genotyped 15 single nucleotide polymorphisms (SNPs) in TSLP, OX40L, IL7R, and RXRα in three independent cohorts: 592 asthmatic Costa Rican children and their parents, 422 nuclear families of North American children with asthma, and 239 Swedish children with asthma. We tested for associations between these SNPs and AR. As we previously reported sex-specific effects for TSLP, we performed overall and sex-stratified analyses. We additionally performed secondary analyses for gene-by-gene interactions.Results
Across the three cohorts, the T allele of TSLP SNP rs1837253 was undertransmitted in boys with AR and asthma as compared to boys with asthma alone. The SNP was associated with reduced odds for AR (odds ratios ranging from 0.56 to 0.63, with corresponding Fisher's combined P value of 1.2 × 10-4). Our findings were significant after accounting for multiple comparisons. SNPs in OX40L, IL7R, and RXRα were not consistently associated with AR in children with asthma. There were nominally significant interactions between gene pairs.Conclusions
TSLP SNP rs1837253 is associated with reduced odds for AR in boys with asthma. Our findings support a role for TSLP in the pathogenesis of AR in children with asthma. 相似文献2.
Baye TM Butsch Kovacic M Biagini Myers JM Martin LJ Lindsey M Patterson TL He H Ericksen MB Gupta J Tsoras AM Lindsley A Rothenberg ME Wills-Karp M Eissa NT Borish L Khurana Hershey GK 《PloS one》2011,6(2):e16522
Background
Candidate gene case-control studies have identified several single nucleotide polymorphisms (SNPs) that are associated with asthma susceptibility. Most of these studies have been restricted to evaluations of specific SNPs within a single gene and within populations from European ancestry. Recently, there is increasing interest in understanding racial differences in genetic risk associated with childhood asthma. Our aim was to compare association patterns of asthma candidate genes between children of European and African ancestry.Methodology/Principal Findings
Using a custom-designed Illumina SNP array, we genotyped 1,485 children within the Greater Cincinnati Pediatric Clinic Repository and Cincinnati Genomic Control Cohort for 259 SNPs in 28 genes and evaluated their associations with asthma. We identified 14 SNPs located in 6 genes that were significantly associated (p-values <0.05) with childhood asthma in African Americans. Among Caucasians, 13 SNPs in 5 genes were associated with childhood asthma. Two SNPs in IL4 were associated with asthma in both races (p-values <0.05). Gene-gene interaction studies identified race specific sets of genes that best discriminate between asthmatic children and non-allergic controls.Conclusions/Significance
We identified IL4 as having a role in asthma susceptibility in both African American and Caucasian children. However, while IL4 SNPs were associated with asthma in asthmatic children with European and African ancestry, the relative contributions of the most replicated asthma-associated SNPs varied by ancestry. These data provides valuable insights into the pathways that may predispose to asthma in individuals with European vs. African ancestry. 相似文献3.
Background
Decreased epinephrine (EPI) is an important underlying factor of bronchoconstriction in asthma. Exogenous β2-adrenergic receptor agonist is one of the preferred options to treat asthma. We previously showed that this phenomenon involved adrenal medullary chromaffin cell (AMCC) transformation to a neuron phenotype. However, the underlying molecular mechanism is not fully understood. To further explore this, an asthmatic model with unilateral adrenalectomy was established in this study.Methodology/Principal Findings
Thirty-two rats were randomly into four groups (n = 8 each) control rats (controls), unilateral adrenalectomy rats (surgery-control, s-control), asthmatic rats (asthma), unilateral adrenalectomy asthmatic rats (surgery-induced asthma, s-asthma). Asthmatic rats and s-asthmatic rats were sensitized and challenged with ovalbumin (OVA). The pathological changes in adrenal medulla tissues were observed under microscopy. EPI and its rate-limiting enzyme, phenylethanolamine N-methyl transferase (PNMT), were measured. Peripherin, a type III intermediate filament protein, was also detected in each group. The asthmatic rats presented with decreased chromaffin granules and swollen mitochondria in AMCCs, and the s-asthmatic rats presented more serious pathological changes than those in asthmatic rats and s-control rats. The expressions of EPI and PNMT in asthmatic rats were significantly decreased, as compared with levels in controls (P<0.05), and a further decline was observed in s-asthmatic rats (P<0.05). The expression of peripherin was higher in the asthmatic rats than in the controls, and the highest level was found in the s-asthmatic rats (P<0.05).Conclusion/Significance
Compared with asthmatic rats and s-control rats, the transformation tendency of AMCCs to neurons is more obvious in the s-asthmatic rats. Moreover, this phenotype alteration in the asthmatic rats is accompanied by reduced EPI and PNMT, and increased peripherin expression. This result provides further evidence to support the notion that phenotype alteration of AMCCs contributes to asthma pathogenesis. 相似文献4.
Amandine Vargas Roxane Boivin Patricia Cano Yoana Murcia Isabelle Bazin Jean-Pierre Lavoie 《Respiratory research》2017,18(1):207
Background
Severe neutrophilic asthma is poorly responsive to glucocorticosteroids (GC). Neutrophil extracellular traps (NETs) within the lungs have been associated with the severity of airway obstruction and inflammation in asthma, and were found to be unaffected by GC in vitro. As IL-17 is overexpressed in neutrophilic asthma and contributes to steroid insensitivity in different cell types, we hypothesized that NETs formation in asthmatic airways would be resistant to GC through an IL-17 mediated pathway.Methods
Six neutrophilic severe asthmatic horses and six healthy controls were studied while being treated with dexamethasone. Lung function, bronchoalveolar lavage fluid (BALF) cytology and NETs formation, as well as the expression of CD11b and CD13 by blood and airway neutrophils were evaluated. The expression of IL-17 and its role in NETs formation were also studied.Results
Airway neutrophils from asthmatic horses, as opposed to blood neutrophils, enhanced NETs formation, which was then decreased by GC. GC also tended to decrease the expression of CD11b in blood neutrophils, but not in airway neutrophils. IL-17 mRNA was increased in BALF cells of asthmatic horses and was unaffected by GC. However, both GC and IL-17 inhibited NETs formation in vitro.Conclusion
GC decreased NETs formation in vitro and also in vivo in the lungs of asthmatic horses. However, airway neutrophil activation during asthmatic inflammation was otherwise relatively insensitive to GC. The contribution of IL-17 to these responses requires further study.5.
Kovacic MB Myers JM Wang N Martin LJ Lindsey M Ericksen MB He H Patterson TL Baye TM Torgerson D Roth LA Gupta J Sivaprasad U Gibson AM Tsoras AM Hu D Eng C Chapela R Rodríguez-Santana JR Rodríguez-Cintrón W Avila PC Beckman K Seibold MA Gignoux C Musaad SM Chen W Burchard EG Hershey GK 《PloS one》2011,6(8):e23714
Background
Asthma is a chronic inflammatory disease with a strong genetic predisposition. A major challenge for candidate gene association studies in asthma is the selection of biologically relevant genes.Methodology/Principal Findings
Using epithelial RNA expression arrays, HapMap allele frequency variation, and the literature, we identified six possible candidate susceptibility genes for childhood asthma including ADCY2, DNAH5, KIF3A, PDE4B, PLAU, SPRR2B. To evaluate these genes, we compared the genotypes of 194 predominantly tagging SNPs in 790 asthmatic, allergic and non-allergic children. We found that SNPs in all six genes were nominally associated with asthma (p<0.05) in our discovery cohort and in three independent cohorts at either the SNP or gene level (p<0.05). Further, we determined that our selection approach was superior to random selection of genes either differentially expressed in asthmatics compared to controls (p = 0.0049) or selected based on the literature alone (p = 0.0049), substantiating the validity of our gene selection approach. Importantly, we observed that 7 of 9 SNPs in the KIF3A gene more than doubled the odds of asthma (OR = 2.3, p<0.0001) and increased the odds of allergic disease (OR = 1.8, p<0.008). Our data indicate that KIF3A rs7737031 (T-allele) has an asthma population attributable risk of 18.5%. The association between KIF3A rs7737031 and asthma was validated in 3 independent populations, further substantiating the validity of our gene selection approach.Conclusions/Significance
Our study demonstrates that KIF3A, a member of the kinesin superfamily of microtubule associated motors that are important in the transport of protein complexes within cilia, is a novel candidate gene for childhood asthma. Polymorphisms in KIF3A may in part be responsible for poor mucus and/or allergen clearance from the airways. Furthermore, our study provides a promising framework for the identification and evaluation of novel candidate susceptibility genes. 相似文献6.
7.
Background
Hypersecretion of cytokines and serine proteinases has been observed in asthma. Since protease-activated receptors (PARs) are receptors of several serine proteinases and airway epithelial cells are a major source of cytokines, the influence of serine proteinases and PARs on interleukin (IL)-8 secretion and gene expression in cultured A549 cells was examined. 相似文献8.
Background
Osteopontin (OPN) is a member of the small integrin-binding ligand N-linked glycoprotein (SIBLING) family and a cytokine with diverse biologic roles. OPN undergoes extensive post-translational modifications, including polymerization and proteolytic fragmentation, which alters its biologic activity. Recent studies suggest that OPN may contribute to the pathogenesis of asthma.Methodology
To determine whether secreted OPN (sOPN) is polymerized in human airways and whether it is qualitatively different in asthma, we used immunoblotting to examine sOPN in bronchoalveolar lavage (BAL) fluid samples from 12 healthy and 21 asthmatic subjects (and in sputum samples from 27 healthy and 21 asthmatic subjects). All asthmatic subjects had mild to moderate asthma and abstained from corticosteroids during the study. Furthermore, we examined the relationship between airway sOPN and cellular inflammation.Principal Findings
We found that sOPN in BAL fluid and sputum exists in polymeric, monomeric, and cleaved forms, with most of it in polymeric form. Compared to healthy subjects, asthmatic subjects had proportionately less polymeric sOPN and more monomeric and cleaved sOPN. Polymeric sOPN in BAL fluid was associated with increased alveolar macrophage counts in airways in all subjects.Conclusions
These results suggest that sOPN in human airways (1) undergoes extensive post-translational modification by polymerization and proteolytic fragmentation, (2) is more fragmented and less polymerized in subjects with mild to moderate asthma, and (3) may contribute to recruitment or survival of alveolar macrophages. 相似文献9.
Wendy A Neveu Jenna L Allard Danielle M Raymond Lorraine M Bourassa Stephanie M Burns Janice Y Bunn Charles G Irvin David A Kaminsky Mercedes Rincon 《Respiratory research》2010,11(1):28
Background
Asthma is a chronic inflammatory disease of the airway that is characterized by a Th2-type of immune response with increasing evidence for involvement of Th17 cells. The role of IL-6 in promoting effector T cell subsets suggest that IL-6 may play a functional role in asthma. Classically IL-6 has been viewed as an inflammatory marker, along with TNFα and IL-1β, rather than as regulatory cytokine.Objective
To investigate the potential relationship between IL-6 and other proinflammatory cytokines, Th2/Th17 cytokines and lung function in allergic asthma, and thus evaluate the potential role of IL-6 in this disease.Methods
Cytokine levels in induced sputum and lung function were measured in 16 healthy control and 18 mild-moderate allergic asthmatic subjects.Results
The levels of the proinflammatory biomarkers TNFα and IL-1β were not different between the control and asthmatic group. In contrast, IL-6 levels were specifically elevated in asthmatic subjects compared with healthy controls (p < 0.01). Hierarchical regression analysis in the total study cohort indicates that the relationship between asthma and lung function could be mediated by IL-6. Among Th2 cytokines only IL-13 (p < 0.05) was also elevated in the asthmatic group, and positively correlated with IL-6 levels (rS = 0.53, p < 0.05).Conclusions
In mild-moderate asthma, IL-6 dissociates from other proinflammatory biomarkers, but correlates with IL-13 levels. Furthermore, IL-6 may contribute to impaired lung function in allergic asthma. 相似文献10.
Dottorini T Sole G Nunziangeli L Baldracchini F Senin N Mazzoleni G Proietti C Balaci L Crisanti A 《PloS one》2011,6(8):e22319
Background
Epidemiological evidence indicates that atopic asthma correlates with high serum IgE levels though the contribution of allergen specific IgE to the pathogenesis and the severity of the disease is still unclear.Methods
We developed a microarray immunoassay containing 103 allergens to study the IgE reactivity profiles of 485 asthmatic and 342 non-asthmatic individuals belonging to families whose members have a documented history of asthma and atopy. We employed k-means clustering, to investigate whether a particular IgE reactivity profile correlated with asthma and other atopic conditions such as rhinitis, conjunctivitis and eczema.Results
Both case-control and parent-to-siblings analyses demonstrated that while the presence of specific IgE against individual allergens correlated poorly with pathological conditions, particular reactivity profiles were significantly associated with asthma (p<10E-09). An artificial neural network (ANN)-based algorithm, calibrated with the profile reactivity data, correctly classified as asthmatic or non-asthmatic 78% of the individual examined. Multivariate statistical analysis demonstrated that the familiar relationships of the study population did not affect the observed correlations.Conclusions
These findings indicate that asthma is a higher-order phenomenon related to patterns of IgE reactivity rather than to single antibody reactions. This notion sheds new light on the pathogenesis of the disease and can be readily employed to distinguish asthmatic and non-asthmatic individuals on the basis of their serum reactivity profile. 相似文献11.
Martin LJ Gupta J Jyothula SS Butsch Kovacic M Biagini Myers JM Patterson TL Ericksen MB He H Gibson AM Baye TM Amirisetty S Tsoras AM Sha Y Eissa NT Hershey GK 《PloS one》2012,7(4):e33454
Rationale and Objective
Autophagy is a cellular process directed at eliminating or recycling cellular proteins. Recently, the autophagy pathway has been implicated in immune dysfunction, the pathogenesis of inflammatory disorders, and response to viral infection. Associations between two genes in the autophagy pathway, ATG5 and ATG7, with childhood asthma were investigated.Methods
Using genetic and experimental approaches, we examined the association of 13 HapMap-derived tagging SNPs in ATG5 and ATG7 with childhood asthma in 312 asthmatic and 246 non-allergic control children. We confirmed our findings by using independent cohorts and imputation analysis. Finally, we evaluated the functional relevance of a disease associated SNP.Measurements and Main Results
We demonstrated that ATG5 single nucleotide polymorphisms rs12201458 and rs510432 were associated with asthma (p = 0.00085 and 0.0025, respectively). In three independent cohorts, additional variants in ATG5 in the same LD block were associated with asthma (p<0.05). We found that rs510432 was functionally relevant and conferred significantly increased promotor activity. Furthermore, Atg5 expression was increased in nasal epithelium of acute asthmatics compared to stable asthmatics and non-asthmatic controls.Conclusion
Genetic variants in ATG5, including a functional promotor variant, are associated with childhood asthma. These results provide novel evidence for a role for ATG5 in childhood asthma. 相似文献12.
Fabio Bucchieri Antonella Marino Gammazza Alessandro Pitruzzella Alberto Fucarino Felicia Farina Peter Howarth Stephen T. Holgate Giovanni Zummo Donna E. Davies 《PloS one》2015,10(3)
Background
Epidemiologic studies have demonstrated important links between air pollution and asthma. Amongst these pollutants, environmental cigarette smoke is a risk factor both for asthma pathogenesis and exacerbation. As the barrier to the inhaled environment, the bronchial epithelium is a key structure that is exposed to cigarette smoke.Objectives
Since primary bronchial epithelial cells (PBECs) from asthmatic donors are more susceptible to oxidant-induced apoptosis, we hypothesized that they would be susceptible to cigarette smoke-induced cell death.Methods
PBECs from normal and asthmatic donors were exposed to cigarette smoke extract (CSE); cell survival and apoptosis were assessed by fluorescence-activated cell sorting, and protective effects of antioxidants evaluated. The mechanism of cell death was evaluated using caspase inhibitors and immunofluorescent staining for apoptosis-inducing factor (AIF).Results
Exposure of PBEC cultures to CSE resulted in a dose-dependent increase in cell death. At 20% CSE, PBECs from asthmatic donors exhibited significantly more apoptosis than cells from non-asthmatic controls. Reduced glutathione (GSH), but not ascorbic acid (AA), protected against CSE-induced apoptosis. To investigate mechanisms of CSE-induced apoptosis, caspase-3 or -9 inhibitors were tested, but these failed to prevent apoptosis; in contrast, CSE promoted nuclear translocation of AIF from the mitochondria. GSH reduced the number of nuclear-AIF positive cells whereas AA was ineffective.Conclusion
Our results show that PBECs from asthmatic donors are more susceptible to CSE-induced apoptosis. This response involves AIF, which has been implicated in DNA damage and ROS-mediated cell-death. Epithelial susceptibility to CSE may contribute to the impact of environmental tobacco smoke in asthma. 相似文献13.
Mohsen Tehrani Abdol-Reza Varasteh Mohammad Reza Khakzad Majid Mirsadraee Mojtaba Sankian 《Reports of Biochemistry & Molecular Biology》2012,1(1):30-36
Background:
Recently, reports have indicated a role for the membrane form of Toll-like Receptor 2 (TLR2) in asthma pathogenesis. In this study we examined soluble TLR2 levels in serum and sputum of asthmatic and healthy subjects.Methods:
Serum and sputum samples were obtained from 33 asthmatic and 19 healthy subjects. The asthmatics were classified into four groups according to the Global Initiative for Asthma. A sandwich ELISA was developed to measure soluble TLR2 (sTLR2) in serum and sputum. TLR2 mRNA expression was determined by semi-quantitative RT-PCR of all sputum samples.Results:
The mean sTLR2 levels from serum and sputum of asthmatics were significantly lower than those from healthy subjects. Moreover, sTLR2 concentration decreased concomitantly with asthma severity. The differences observed, however, were not statistically significant. TLR2/GAPDH mRNA of sputum leukocytes was also significantly lower in asthmatics than in healthy subjects.Conclusion:
This study demonstrated for the first time thatsTLR2 levels are lower in serum and sputum samples from asthmatic than from healthy subjects, and this could be an indicator of TLR2 expression. We also found that sTLR2 concentration in serum decreased concomitantly with an increase of asthma severity clinical score. Key Words: Asthma, Expression, TLR2 mRNA, Soluble Toll-like receptor 相似文献14.
Matthew J Loza Susan Foster Eugene R Bleecker Stephen P Peters Raymond B Penn 《Respiratory research》2010,11(1):103
Background
The "Th2 hypothesis for asthma" asserts that an increased ratio of Th2:Th1 cytokine production plays an important pathogenic role in asthma. Although widely embraced, the hypothesis has been challenged by various empirical observations and has been described as overly simplistic. We sought to establish whether CD3+CD28-mediated and antigen-independent accumulation of type 1 and type 2 T cells differs significantly between nonasthmatic and asthmatic populations.Methods
An ex vivo system was used to characterize the regulation of IFN-γ-producing (type 1) and IL-13-producing (type 2) T cell accumulation in response to CD3+CD28 and IL-2 stimulation by flow cytometry.Results
IL-13-producing T cells increased in greater numbers in response to antigen-independent stimulation in peripheral blood lymphocytes from female atopic asthmatic subjects compared with male asthmatics and both male and female atopic non-asthmatic subjects. IFN-γ+ T cells increased in greater numbers in response to either antigen-independent or CD3+CD28-mediated stimulation in peripheral blood lymphocytes from atopic asthmatic subjects compared to non-asthmatic subjects, regardless of gender.Conclusions
We demonstrate that T cells from asthmatics are programmed for increased accumulation of both type 2 and type 1 T cells. Gender had a profound effect on the regulation of type 2 T cells, thus providing a mechanism for the higher frequency of adult asthma in females. 相似文献15.
M. S. Magnoni M. Caminati G. W. Canonica F. Arpinelli A. Rizzi G. Senna 《Clinical and molecular allergy : CMA》2017,15(1):11
Background
In Europe more than 50% of asthmatic treated patients have not well-controlled asthma. Asthma affects about 2.5 million of patients in Italy.Aims and objectives
The present survey aims at investigating how Italian allergists approach asthmatic patients, in order to highlight pitfalls and unmet needs concerning real-life asthma management.Methods
An anonymous 16 item web questionnaire was available (April–October 2015) to all allergists who visited the web site of SIAAIC (Società Italiana di Allergologia, Asma Immunologia Clinica). Those who wished to give their contribution had the opportunity to answer about epidemiology, risk factors, treatment approaches, and adherence to therapy.Results
One hundred and seventy four allergists answered the survey. 54% of them reported up to 10 patient visits per week and 35.3% between 10 and 30. The most frequent reasons of follow up visits are routine check-up (56.5% of allergists), and worsening of symptoms (41% of allergists). Nocturnal apnoeas, gastro-esophageal reflux and obesity are the most important comorbidities/risk factors of poorly controlled asthma. Bronchial hyper-responsiveness, increased NO levels and reduced exercise tolerance are the most important indicators of asthma severity. Concerning therapy, ICS combined with LABA is the treatment of choice suitable for the majority of patients. A rapid onset of action and a flexible ICS dosage are indicated as the optimal characteristics for achieving the therapeutic goals. Poor adherence to therapy is an important reason for symptom worsening for the majority of allergists. Complex dosage regimens and economic aspects are considered the most important factors impacting on adherence.Conclusions
Allergists are involved in the management of asthma, regularly seeing their patients. Co-morbidities are frequent in asthmatic patients and may impact negatively on disease control, thus identifying patients who need a more careful and strict monitoring. Airway hyper-responsiveness to methacholine challenge test and nitric oxide are considered important indicators of asthma severity. The combination of LABA and inhaled steroids is considered the treatment of choice for most asthmatic patients, in keeping with broad evidence indicating that the combination therapy is more effective and rapid in gaining asthma control than inhaled corticosteroids alone. Adherence to medication regimens is considered of essence to achieve the therapeutic goals.16.
Yu-Kuei Teng Jing-Long Huang Kuo-Wei Yeh Lin-Shien Fu Chia-Huei Lin Wei-Fen Ma Shin-Da Lee Li-Chi Chiang 《PloS one》2014,9(12)
Purpose
Little research has been reported concerning insufficient physical activity in Taiwanese adolescents with asthma. The aims of this paper are to compare the amount of physical activity between asthmatic and non-asthmatic adolescents in Taiwan, as well as to investigate the influential factors associated with insufficient physical activity in asthmatic adolescents.Methods
Self-reporting structured questionnaires (socio-economic status, scale of family support for physical activity, amount of physical activity) and peak expiratory flow were assessed from 286 adolescents with asthma and 588 non-asthmatic adolescents in a cross-sectional design. Insufficient amount of physical activity was based on less than 300 minutes per week of moderate and vigorous physical activity.Results
Adolescents with asthma have a greater amount of physical activity and a higher level of family support than those who are non-asthmatic. In Taiwan, adolescents with asthma, girls relative to boys, obesity relative to average weight, and low family support relative to high family support were found to be associated with insufficient physical activity.Conclusion
Physical activity in adolescents with asthma is insufficient especially in girls, in asthmatics with obesity, and in those with low family support. We suggest that physical activity programs should be applied to Taiwan adolescents with asthma in order to match the criteria of 300 minutes per week of moderate and vigorous physical activity, especially for girls, the obese and those with a low level of family support. 相似文献17.
Ziemowit Zietkowski Roman Skiepko Maria M Tomasiak Anna Bodzenta-Lukaszyk 《Respiratory research》2007,8(1):76-9
Background
Exercise-induced bronchoconstriction (EIB) is a highly prevalent condition, whose pathophysiology is not well understood. Endothelins are proinflammatory, profibrotic, broncho- and vasoconstrictive peptides which play an important role in the development of airway inflammation and remodeling in asthma. The aim of the study was to evaluate the changes in endothelin-1 levels in exhaled breath condensate following intensive exercise in asthmatic patients.Methods
The study was conducted in a group of 19 asthmatic patients (11 with EIB, 8 without EIB) and 7 healthy volunteers. Changes induced by intensive exercise in the concentrations of endothelin-1 (ET-1) in exhaled breath condensate (EBC) during 24 hours after an exercise challenge test were determined. Moreover, the possible correlations of these measurements with the results of other tests commonly associated with asthma and with the changes of airway inflammation after exercise were observed.Results
In asthmatic patients with EIB a statistically significant increase in the concentration of ET-1 in EBC collected between 10 minutes and 6 hours after an exercise test was observed. The concentration of ET-1 had returned to its initial level 24 hours after exercise. No effects of the exercise test on changes in the concentrations of ET-1 in EBC in either asthmatic patients without EIB or healthy volunteers were observed. A statistically significant correlation between the maximum increase in ET-1 concentrations in EBC after exercise and either baseline FENO and the increase in FENO or BHR to histamine 24 hours after exercise in the groups of asthmatics with EIB was revealed.Conclusion
The release of ET-1 from bronchial epithelium through the influence of many inflammatory cells essential in asthma and interactions with other cytokines, may play an important role in increase of airway inflammation which was observed after postexercise bronchoconstriction in asthmatic patients. 相似文献18.
Lionel Loubaki Ikhlass Hadj-Salem Raouia Fakhfakh Eric Jacques Sophie Plante Marc Boisvert Fawzi Aoudjit Jamila Chakir 《PloS one》2013,8(12)
Background
Airway inflammation is an important characteristic of asthma and has been associated with airway remodelling and bronchial hyperreactivity. The mucosal microenvironment composed of structural cells and highly specialised extracellular matrix is able to amplify and promote inflammation. This microenvironment leads to the development and maintenance of a specific adaptive response characterized by Th2 and Th17. Bronchial fibroblasts produce multiple mediators that may play a role in maintaining and amplifying this response in asthma.Objective
To investigate the role of bronchial fibroblasts obtained from asthmatic subjects and healthy controls in regulating Th17 response by creating a local micro-environment that promotes this response in the airways.Methods
Human bronchial fibroblasts and CD4+T cells were isolated from atopic asthmatics and non-atopic healthy controls. CD4+T were co-cultured with bronchial fibroblasts of asthmatic subjects and healthy controls. RORc gene expression was detected by qPCR. Phosphorylated STAT-3 and RORγt were evaluated by western blots. Th17 phenotype was measured by flow cytometry. IL-22, IL17, IL-6 TGF-β and IL1-β were assessed by qPCR and ELISA.Results
Co-culture of CD4+T cells with bronchial fibroblasts significantly stimulated RORc expression and induced a significant increase in Th17 cells as characterized by the percentage of IL-17+/CCR6+ staining in asthmatic conditions. IL-17 and IL-22 were increased in both normal and asthmatic conditions with a significantly higher amount in asthmatics compared to controls. IL-6, IL-1β, TGF-β and IL-23 were significantly elevated in fibroblasts from asthmatic subjects upon co-culture with CD4+T cells. IL-23 stimulates IL-6 and IL-1β expression by bronchial fibroblasts.Conclusion
Interaction between bronchial fibroblasts and T cells seems to promote specifically Th17 cells profile in asthma. These results suggest that cellular interaction particularly between T cells and fibroblasts may play a pivotal role in the regulation of the inflammatory response in asthma. 相似文献19.
Comhair SA Gaston BM Ricci KS Hammel J Dweik RA Teague WG Meyers D Ampleford EJ Bleecker ER Busse WW Calhoun WJ Castro M Chung KF Curran-Everett D Israel E Jarjour WN Moore W Peters SP Wenzel S Hazen SL Erzurum SC;National Heart Lung Blood Institute Severe Asthma Research Program 《PloS one》2011,6(5):e18574
Background
Environmental tobacco smoke (ETS) has adverse effects on the health of asthmatics, however the harmful consequences of ETS in relation to asthma severity are unknown.Methods
In a multicenter study of severe asthma, we assessed the impact of ETS exposure on morbidity, health care utilization and lung functions; and activity of systemic superoxide dismutase (SOD), a potential oxidative target of ETS that is negatively associated with asthma severity.Findings
From 2002–2006, 654 asthmatics (non-severe 366, severe 288) were enrolled, among whom 109 non-severe and 67 severe asthmatics were routinely exposed to ETS as ascertained by history and validated by urine cotinine levels. ETS-exposure was associated with lower quality of life scores; greater rescue inhaler use; lower lung function; greater bronchodilator responsiveness; and greater risk for emergency room visits, hospitalization and intensive care unit admission. ETS-exposure was associated with lower levels of serum SOD activity, particularly in asthmatic women of African heritage.Interpretation
ETS-exposure of asthmatic individuals is associated with worse lung function, higher acuity of exacerbations, more health care utilization, and greater bronchial hyperreactivity. The association of diminished systemic SOD activity to ETS exposure provides for the first time a specific oxidant mechanism by which ETS may adversely affect patients with asthma. 相似文献20.
Gerald B. Lee Eric B. Brandt Chang Xiao Aaron M. Gibson Timothy D. Le Cras Lou Ann S. Brown Anne M. Fitzpatrick Gurjit K. Khurana Hershey 《PloS one》2013,8(3)