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(American Journal of Pathology. 2004;165:1097-1106.)
© 2004 American Society for Investigative Pathology

Transforming Growth Factor-ß2 Induces Bronchial Epithelial Mucin Expression in Asthma

Hong Wei Chu^*, Silvana Balzar^*, Gregory J. Seedorf, Jay Y. Westcott^*, John B. Trudeau^*, Phil Silkoff^* and Sally E. Wenzel^*

From the Department of Medicine,^* National Jewish Medical and Research Center, Denver; and the University of Colorado Health Sciences Center, Denver, Colorado

The transforming growth factor (TGF)-ß family is important for tissue repair in pathological conditions including asthma. However, little is known about the impact of either TGF-ß1 or TGF-ß2 on asthmatic airway epithelial mucin expression. We evaluated bronchial epithelial TGF-ß1 and TGF-ß2 expression and their effects on mucin expression, and the role of TGF-ß1 or TGF-ß2 in interleukin (IL)-13-induced mucin expression. Epithelial TGF-ß1, TGF-ß2, and mucin expression were evaluated in endobronchial biopsies from asthmatics and normal subjects. The effects of TGF-ß1 or TGF-ß2 on mucin MUC5AC protein and mRNA expression, and the impact of IL-13 on epithelial TGF-ß1, TGF-ß2, and MUC5AC were determined in cultured bronchial epithelial cells from endobronchial brushings of both subject groups. In biopsy tissue, epithelial TGF-ß2 expression levels were higher than TGF-ß1 in both asthmatics and normals. TGF-ß2, but not TGF-ß1, was increased in asthmatics compared with normals, and significantly correlated with mucin expression. TGF-ß2, but not TGF-ß1, increased mucin expression in cultured epithelial cells from both subject groups. IL-13 increased the release of TGF-ß2, but not TGF-ß1, from epithelial cells. A neutralizing TGF-ß2 antibody partially inhibited IL-13-induced mucin expression. These data suggest that TGF-ß2 production by asthmatic bronchial epithelial cells may increase airway mucin expression. IL-13-induced mucin expression may occur in part through TGF-ß2 up-regulation.

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