• Decrease font size
  • Return font size to normal
  • Increase font size
U.S. Department of Health and Human Services

Scientific Publications by FDA Staff

  • Print
  • Share
  • E-mail

Search Publications



Starting Date

Ending Date

Order by

Entry Details

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

IL-13 signaling through the IL-13alpha(2) receptor is involved in induction of TGF-beta(1) production and fibrosis.

Fichtner-Feigl S, Strober W, Kawakami K, Puri RK, Kitani A

Strober W, NIAID, NIH, Mucosal Immun Sect, Lab Host Def, Bldg 10-CRC 5W3864,10 Ctr Dr, Bethesda, MD 20892 USA NIAID, NIH, Mucosal Immun Sect, Lab Host Def, Bethesda, MD 20892 USA Univ Regensburg, Dept Surg, Med Ctr, D-93053 Regensburg, Germany US FDA, Lab Mol Tumor Biol, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res,NIH, Bethesda, MD 20892 USA


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.

Category: Journal Article
PubMed ID: #16327802
Includes FDA Authors from Scientific Area(s): Biologics
Entry Created: 2011-10-04 Entry Last Modified: 2012-08-29