TY - JOUR
T1 - Chitinase 3-like 1 regulates cellular and tissue responses via IL-13 receptor α2
AU - He, Chuan Hua
AU - Lee, Chun Geun
AU - DelaCruz, Charles S.
AU - Lee, Chang Min
AU - Zhou, Yang
AU - Ahangari, Farida
AU - Ma, Bing
AU - Herzog, Erica L.
AU - Rosenberg, Stephen A.
AU - Li, Yue
AU - Nour, Adel M.
AU - Parikh, Chirag R.
AU - Schmidt, Insa
AU - Modis, Yorgo
AU - Cantley, Lloyd
AU - Elias, Jack A.
N1 - Funding Information:
This work was supported by NIH grants (R01-HL-093017 and U01-HL-108638 to J.A.E.; P01 GM022778 and R01 GM102869 to Y.M.) and by a Burroughs Wellcome Investigator in the Pathogenesis of Infectious Disease Award to Y.M. The T100 Biacore instrumentation was supported by NIH award S10RR026992-0110.
PY - 2013/8/29
Y1 - 2013/8/29
N2 - 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 inantipathogen 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
AB - 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 inantipathogen 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
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U2 - 10.1016/j.celrep.2013.07.032
DO - 10.1016/j.celrep.2013.07.032
M3 - Article
C2 - 23972995
AN - SCOPUS:84883265444
SN - 2211-1247
VL - 4
SP - 830
EP - 841
JO - Cell Reports
JF - Cell Reports
IS - 4
ER -