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

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 (...

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Bibliographic Details
Published in:Clinical immunology (Orlando, Fla.) Fla.), 2011-09, Vol.140 (3), p.268-275
Main Authors: Chen, Chun-Chuan, Llado, Victoria, Eurich, Katrin, Tran, Hoa T, Mizoguchi, Emiko
Format: Article
Language:English
Subjects:
Allergy and Immunology
Amino Acid Motifs
Animals
Biological and medical sciences
Cell Line
Chitin-binding motifs
Chitinase-3-Like Protein 1
Chitinases
Colon - enzymology
Epithelial cells
Epithelial Cells - metabolism
Fundamental and applied biological sciences. Psychology
Fundamental immunology
Glycoproteins - metabolism
Humans
Interleukin-8 - biosynthesis
Mice
Proto-Oncogene Proteins c-akt - metabolism
Signal Transduction
Tumor Necrosis Factor-alpha - metabolism
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Summary: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.
ISSN:1521-6616
1521-7035
DOI:10.1016/j.clim.2011.04.007