IL-13 signaling through the IL-13alpha2 receptor is involved in induction of TGF-beta1 production and fibrosis - PubMed (original) (raw)

doi: 10.1038/nm1332. Epub 2005 Dec 4.

Affiliations

PMID: 16327802
DOI: 10.1038/nm1332

IL-13 signaling through the IL-13alpha2 receptor is involved in induction of TGF-beta1 production and fibrosis

Stefan Fichtner-Feigl et al. Nat Med. 2006 Jan.

Abstract

Interleukin (IL)-13 is a major inducer of fibrosis in many chronic infectious and autoimmune diseases. In studies of the mechanisms underlying such induction, we found that IL-13 induces transforming growth factor (TGF)-beta(1) in macrophages through a two-stage process involving, first, the induction of a receptor formerly considered to function only as a decoy receptor, IL-13Ralpha(2). Such induction requires IL-13 (or IL-4) and tumor necrosis factor (TNF)-alpha. Second, it involves IL-13 signaling through IL-13Ralpha(2) to activate an AP-1 variant containing c-jun and Fra-2, which then activates the TGFB1 promoter. In vivo, we found that prevention of IL-13Ralpha(2) expression reduced production of TGF-beta(1) in oxazolone-induced colitis and that prevention of IL-13Ralpha(2) expression, Il13ra2 gene silencing or blockade of IL-13Ralpha(2) signaling led to marked downregulation of TGF-beta(1) production and collagen deposition in bleomycin-induced lung fibrosis. These data suggest that IL-13Ralpha(2) signaling during prolonged inflammation is an important therapeutic target for the prevention of TGF-beta(1)-mediated fibrosis.

PubMed Disclaimer

Comment in

Decoy receptor springs to life and eases fibrosis.
MacDonald TT. MacDonald TT. Nat Med. 2006 Jan;12(1):13-4. doi: 10.1038/nm0106-13. Nat Med. 2006. PMID: 16397542 No abstract available.

IL-13 signaling through the IL-13alpha2 receptor is involved in induction of TGF-beta1 production and fibrosis - PubMed (original) (raw)