Transforming growth factor-beta2 induces bronchial epithelial mucin expression in asthma.
The transforming growth factor (TGF)-beta family is important for tissue repair in pathological conditions including asthma. However, little is known about the impact of either TGF-beta1 or TGF-beta2 on asthmatic airway epithelial mucin expression. We evaluated bronchial epithelial TGF-beta1 and TGF-beta2 expression and their effects on mucin expression, and the role of TGF-beta1 or TGF-beta2 in interleukin (IL)-13-induced mucin expression. Epithelial TGF-beta1, TGF-beta2, and mucin expression were evaluated in endobronchial biopsies from asthmatics and normal subjects. The effects of TGF-beta1 or TGF-beta2 on mucin MUC5AC protein and mRNA expression, and the impact of IL-13 on epithelial TGF-beta1, TGF-beta2, and MUC5AC were determined in cultured bronchial epithelial cells from endobronchial brushings of both subject groups. In biopsy tissue, epithelial TGF-beta2 expression levels were higher than TGF-beta1 in both asthmatics and normals. TGF-beta2, but not TGF-beta1, was increased in asthmatics compared with normals, and significantly correlated with mucin expression. TGF-beta2, but not TGF-beta1, increased mucin expression in cultured epithelial cells from both subject groups. IL-13 increased the release of TGF-beta2, but not TGF-beta1, from epithelial cells. A neutralizing TGF-beta2 antibody partially inhibited IL-13-induced mucin expression. These data suggest that TGF-beta2 production by asthmatic bronchial epithelial cells may increase airway mucin expression. IL-13-induced mucin expression may occur in part through TGF-beta2 up-regulation.
Chu
Hong Wei
HW
Department of Medicine, National Jewish Medical and Research Center, D104, 1400 Jackson St., Denver, CO 80206, USA. chuhw@njc.org.
Balzar
Silvana
S
Seedorf
Gregory J
GJ
Westcott
Jay Y
JY
Trudeau
John B
JB
Silkoff
Phil
P
Wenzel
Sally E
SE
D000328:Adult; D001249:Asthma / Q000378:metabolism*; D001706:Biopsy; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D018793:Interleukin-13 / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D009077:Mucins / Q000096:biosynthesis* / Q000187:drug effects; D020545:Respiratory Mucosa / Q000187:drug effects / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000096:biosynthesis* / Q000187:drug effects / Q000494:pharmacology
D018793:Interleukin-13; D009077:Mucins; D016212:Transforming Growth Factor beta