Abstract:
RATIONALE:Airway remodeling is an important feature of chronic asthma that causes irreversible airflow obstruction. Although asthma is considered to be a Th2 disease, the role of T-bet and GATA-3, the key transcription factors for differentiation toward Th1 and Th2 cells, in the pathogenesis of airway remodeling is poorly understood. OBJECTIVES:We therefore examined the effects of GATA-3 or T-bet induction of Th1/Th2 bias on the development of airway remodeling in mice. METHODS:The development of airway remodeling after repeated allergen challenges was analyzed using transgenic mice overexpressing either GATA-3 or T-bet. MAIN RESULTS:The degrees of subepithelial fibrosis and airway smooth muscle hyperplasia after repeated allergen exposure were significantly enhanced in mice overexpressing GATA-3, compared with wild-type mice. Allergen-induced goblet cell hyperplasia and mucus hypersecretion were significantly lower in mice overexpressing T-bet than in wild-type mice. Eosinophilic airway inflammation increased in mice overexpressing GATA-3, but decreased in mice overexpressing T-bet after repeated allergen exposure. Cytokine analysis revealed that the Th1/Th2 cytokine balance shifted to Th2 in lung homogenates and lung T cells of mice overexpressing GATA-3, whereas this balance shifted to Th1 in those of mice overexpressing T-bet after allergen exposure. Lung transforming growth factor-beta and eotaxin levels were associated with the degree of subepithelial fibrosis and eosinophilic airway inflammation, respectively. CONCLUSIONS:Overall, the results indicate that development of airway remodeling is regulated by the lung Th1/Th2 bias induced by GATA-3 and T-bet.
journal_name
Am J Respir Crit Care Medauthors
Kiwamoto T,Ishii Y,Morishima Y,Yoh K,Maeda A,Ishizaki K,Iizuka T,Hegab AE,Matsuno Y,Homma S,Nomura A,Sakamoto T,Takahashi S,Sekizawa Kdoi
10.1164/rccm.200601-079OCsubject
Has Abstractpub_date
2006-07-15 00:00:00pages
142-51issue
2eissn
1073-449Xissn
1535-4970pii
200601-079OCjournal_volume
174pub_type
杂志文章abstract::Epidemiologic investigation has established an association between exposure to particulate matter (PM) and human health in the Utah Valley. Reduction of particle mass during the temporary closure of a local steel mill was associated with diminished morbidity and mortality. We tested the hypothesis that the biologic ef...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
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