Eosinophil-associated TGF-beta(1) mRNA expression and airways fibrosis in bronchial asthma

被引:546
作者
Minshall, EM
Leung, DYM
Martin, RJ
Song, YL
Cameron, L
Ernst, P
Hamid, Q
机构
[1] MCGILL UNIV, MEAKINS CHRISTIE LABS, MONTREAL, PQ H3X 2P2, CANADA
[2] MCGILL UNIV, EPIDEMIOL UNIT, MONTREAL, PQ, CANADA
[3] NATL JEWISH CTR IMMUNOL & RESP MED, DEPT PEDIAT & MED, DENVER, CO 80206 USA
关键词
D O I
10.1165/ajrcmb.17.3.2733
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The histopathology of bronchial asthma is associated with structural changes within the airways, including subepithelial fibrosis, as well as chronic eosinophilic inflammation. The mechanisms responsible for this tissue remodeling, and in particular the role of inflammatory cells, remain to be established. Transforming growth factor-beta (TGF-beta) is a potent profibrotic cytokine which may contribute to the thickening of the reticular lamina by the deposition of collagen fibers, To investigate the molecular mechanisms underlying these structural changes, we have investigated the expression of TGF-beta(1) mRNA and immunoreactivity within the bronchial mucosa of mild to severe asthmatic individuals and normal control subjects using the techniques of in situ hybridization and immunocytochemistry. As eosinophils are prominent within the asthmatic airway and are known to synthesize pro-inflammatory cytokines, the presence of TGF-beta(1) mRNA and immunoreactive protein in eosinophils was also examined, Asthmatic individuals exhibited a greater expression of TGF-beta(1) mRNA and immunoreactivity in the airways submucosa than normal control subjects (P < 0.05), and these increases were directly related to the severity of the disorder. The extent of airways fibrosis, as detected histochemically, was also increased in asthmatics compared with normal control subjects (P < 0.005). In asthmatic subjects, the presence of subepithelial fibrosis was associated with the severity of the disease and correlated with the decline in forced expiratory volume in 1 s (r(2) = 0.78; P < 0.05). Within the asthmatic airways, EG2-positive eosinophils represented the major source of TGF-beta(1) mRNA and immunoreactivity. These results provide evidence that TGF-beta(1) may play a role in the fibrotic changes occurring within asthmatic airways and that activated eosinophils are a major source of this cytokine.
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页码:326 / 333
页数:8
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