IL-13 signaling through the IL-132 receptor is involved in induction of TGF-1 production and fibrosis (Nat Med, 2006, 12:99-106)

報告日期: 2006/04/11
報告時間: 17:10/18:00
報告學生: 陳威宇 (英文報告)
講評老師: 凌斌
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IL-13 signaling through the IL-13a2 receptor is involved in induction of TGF-b1 production and fibrosis.

Nat Med. 2006 Jan;12(1):99-106.

Speaker: Wei-Yu Chen 陳威宇          2006/4/11 pm 5:00-6:00

Commentator: Pin Ling 凌斌 老師                Room 602

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, the authors found that IL-13 induces transforming growth factor (TGF)-b1 in macrophages through a two-stage process involving, first, the induction of a receptor formerly considered to function only as a decoy receptor, IL-13Ra2. Such induction requires IL-13 (or IL-4) and tumor necrosis factor (TNF)-a. Second, it involves IL-13 signaling through IL-13Ra2 to activate an AP-1 variant containing c-jun and Fra-2, which then activates the TGFB1 promoter. In vivo, they found that prevention of IL-13Ra2 expression reduced production of TGF-b1 in oxazolone-induced colitis. They also found that prevention of IL-13Ra2 expression, Il13ra2 gene silencing or blockade of IL-13Ra2 signaling led to marked downregulation of TGF-b1 production and collagen deposition in bleomycin-induced lung fibrosis. These data suggest that IL-13Ra2 signaling during prolonged inflammation is an important therapeutic target for the prevention of TGF-b1-mediated fibrosis.

References

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