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The FASEB Journal express article 10.1096/fj.03-1492fje. Published online May 20, 2004. IL-13 and IL-1β promote lung fibroblast growth through coordinated up-regulation of PDGF-AA and PDGF-Rα

By Jennifer L. Ingram, Annette B. Rice, Kristen Geisenhoffer, David K. Madtes and James C. Bonner

Abstract

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-Rα, showed no mitogenic response to IL-13. However, Patch cells did exhibit IL-13-induced STAT-6 phosphorylation. Stable transfection of the PDGF-Rα 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-1β enhanced IL-13-induced mitogenesis of rat lung fibroblasts through up-regulation o

Year: 2013
OAI identifier: oai:CiteSeerX.psu:10.1.1.319.6238
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