Fichtner-Feigl, Stefan and Strober, Warren and Kawakami, Koji and Puri, Raj K. and Kitani, Atsushi (2006) IL-13 signaling through the IL-13 alpha 2 receptor is involved in induction of TGF-beta 1 production and fibrosis. NATURE MEDICINE, 12 (1). pp. 99-106. ISSN 1078-8956, 1546-170X
Full text not available from this repository. (Request a copy)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-13R alpha(2). Such induction requires IL-13 (or IL-4) and tumor necrosis factor (TNF)-alpha. Second, it involves IL-13 signaling through IL-13R alpha(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-13R alpha(2) expression reduced production of TGF-beta(1) in oxazolone-induced colitis and that prevention of IL-13Ra2 expression, Il13ra2 gene silencing or blockade of IL-13R alpha(2) signaling led to marked downregulation of TGF-beta(1) production and collagen deposition in bleomycin-induced lung fibrosis. These data suggest that IL-13R alpha(2) signaling during prolonged inflammation is an important therapeutic target for the prevention of TGF-beta(1)-mediated fibrosis.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | GROWTH FACTOR-BETA-1 GENE; NK-T-CELLS; PULMONARY-FIBROSIS; ULCERATIVE-COLITIS; OXAZOLONE COLITIS; TISSUE FIBROSIS; ALPHA-2 CHAIN; IN-VIVO; MICE; INTERLEUKIN-13; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Chirurgie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 03 Mar 2021 07:42 |
| Last Modified: | 03 Mar 2021 07:43 |
| URI: | https://pred.uni-regensburg.de/id/eprint/35231 |
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