Carbohydrate-binding motif in chitinase 3-like 1 (CHI3L1/YKL-40) specifically activates Akt signaling pathway in colonic epithelial cells

Chun Chuan Chen, Victoria Llado, Katrin Eurich, Hoa T. Tran, Emiko Mizoguchi

Research output: Contribution to journalArticlepeer-review

76 Scopus citations

Abstract

Host-microbial interactions play a key role during the development of colitis. We have previously shown that chinase 3-like 1 (CHI3L1) is an inducible molecule overexpressed in colonic epithelial cells (CECs) under inflammatory conditions.In this study, we found that chitin-binding motif (CBM) of CHI3L1 is specifically associated with the CHI3L1-mediated activation of the Akt-signaling in CEC by transfecting the CBM-mutant CHI3L1 vectors in SW480 CECs. Downstream, CHI3L1 enhanced the secretion of IL-8 and TNFα in a dose-dependent manner. We previously show that 325 through 339 amino-acids in CBM are crucial for the biological function of CHI3L1. Here we demonstrated that 325th-339th residues of CBM in CHI3L1 is a critical region for the activation of Akt, IL-8 production, and for a specific cellular localization of CHI3L1.In conclusion, CBM region of CHI3L1 is critical in activating Akt signaling in CECs, and the activation may be associated with the development of chronic colitis.

Original languageEnglish (US)
Pages (from-to)268-275
Number of pages8
JournalClinical Immunology
Volume140
Issue number3
DOIs
StatePublished - Sep 2011
Externally publishedYes

Keywords

  • Chitin-binding motifs
  • Chitinases
  • Epithelial cells
  • Signal transduction

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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