IL-13 and IL-1beta promote lung fibroblast growth through coordinated up-regulation of PDGF-AA and PDGF-Ralpha.

Published

Journal Article

Peribronchiolar fibrosis is a prominent feature of airway remodeling in asthma and involves fibroblast growth and collagen deposition. Interleukin-13 (IL-13), a T-helper 2 cytokine, is a key mediator of airway remodeling in asthma, yet the mechanism through which IL-13 promotes fibroblast growth has not been investigated. In this study, we show that IL-13 stimulates the mitogenesis of mouse, rat, and human lung fibroblasts through release of a soluble mitogen that we identified as PDGF-AA. The IL-13-induced growth of human lung fibroblasts was attenuated by an anti-PDGF-AA neutralizing antibody, and IL-13 stimulated human lung fibroblasts to secrete PDGF-AA. Fibroblasts derived from mouse embryos possessing the lethal Patch mutation, which lack the PDGF-Ralpha, showed no mitogenic response to IL-13. However, Patch cells did exhibit IL-13-induced STAT-6 phosphorylation. Stable transfection of the PDGF-Ralpha into Patch cells restored the growth response to PDGF-AA and IL-13. Through the use of lung fibroblasts from STAT-6-deficient mice, we showed that IL-13-induced PDGF-AA release is STAT-6 dependent, but PDGF-AA-induced growth is STAT-6 independent. Finally, we showed that IL-1beta enhanced IL-13-induced mitogenesis of rat lung fibroblasts through up-regulation of the PDGF-Ralpha. Our findings indicate that IL-13 acts in synergy with IL-1beta to stimulate growth by coordinately up-regulating PDGF-AA and the PDGF-Ralpha, respectively.

Full Text

Duke Authors

Cited Authors

  • Ingram, JL; Rice, AB; Geisenhoffer, K; Madtes, DK; Bonner, JC

Published Date

  • July 1, 2004

Published In

Volume / Issue

  • 18 / 10

Start / End Page

  • 1132 - 1134

PubMed ID

  • 15155567

Pubmed Central ID

  • 15155567

Electronic International Standard Serial Number (EISSN)

  • 1530-6860

Digital Object Identifier (DOI)

  • 10.1096/fj.03-1492fje

Language

  • eng

Conference Location

  • United States