Transforming growth factor-beta2 induces bronchial epithelial mucin expression in asthma

Am J Pathol. 2004 Oct;165(4):1097-106. doi: 10.1016/s0002-9440(10)63371-8.

Abstract

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Asthma / metabolism*
  • Biopsy
  • Cells, Cultured
  • Female
  • Humans
  • Interleukin-13 / pharmacology
  • Male
  • Middle Aged
  • Mucins / biosynthesis*
  • Mucins / drug effects
  • Respiratory Mucosa / drug effects
  • Respiratory Mucosa / metabolism*
  • Transforming Growth Factor beta / biosynthesis*
  • Transforming Growth Factor beta / drug effects
  • Transforming Growth Factor beta / pharmacology

Substances

  • Interleukin-13
  • Mucins
  • Transforming Growth Factor beta