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Cell Rep. 2013 Aug 29;4(4):830-41. doi: 10.1016/j.celrep.2013.07.032. Epub 2013 Aug 22.

Chitinase 3-like 1 regulates cellular and tissue responses via IL-13 receptor α2.

Author information

  • 1Section of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, Yale University School of Medicine, 300 Cedar Street, New Haven, CT 06520-8057, USA.

Erratum in

  • Cell Rep. 2015 Mar 3;10(8):1433.
  • Cell Rep. 2013 Nov 27;5(4):1156.

Abstract

Members of the 18 glycosyl hydrolase (GH 18) gene family have been conserved over species and time and are dysregulated in inflammatory, infectious, remodeling, and neoplastic disorders. This is particularly striking for the prototypic chitinase-like protein chitinase 3-like 1 (Chi3l1), which plays a critical role in antipathogen responses where it augments bacterial killing while stimulating disease tolerance by controlling cell death, inflammation, and remodeling. However, receptors that mediate the effects of GH 18 moieties have not been defined. Here, we demonstrate that Chi3l1 binds to interleukin-13 receptor α2 (IL-13Rα2) and that Chi3l1, IL-13Rα2, and IL-13 are in a multimeric complex. We also demonstrate that Chi3l1 activates macrophage mitogen-activated protein kinase, protein kinase B/AKT, and Wnt/β-catenin signaling and regulates oxidant injury, apoptosis, pyroptosis, inflammasome activation, antibacterial responses, melanoma metastasis, and TGF-β1 production via IL-13Rα2-dependent mechanisms. Thus, IL-13Rα2 is a GH 18 receptor that plays a critical role in Chi3l1 effector responses.

Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

PMID:
23972995
[PubMed - indexed for MEDLINE]
PMCID:
PMC3988532
Free PMC Article
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