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Potential Association Between TLR4 and Chitinase 3-Like 1 (CHI3L1/YKL-40) Signaling on Colonic Epithelial Cells in Inflammatory Bowel Disease and Colitis-Associated Cancer

[ Vol. 13 , Issue. 7 ]

Author(s):

A. Kamba, I.-A. Lee and E. Mizoguchi   Pages 1110 - 1121 ( 12 )

Abstract:


Inflammatory bowel disease (IBD) is a group of inflammatory disorders in the small and large intestines. Several studies have proved that persistent and disregulated host/microbial interactions are required for the development of IBD. It is well known that chronic IBD is strongly associated with an increased risk of developing colorectal cancer by 0.5-1% annually, 8-10 years after the initial diagnosis. To detect the tiny dysplasia or early stage of cancer in chronic IBD patients, a tremendous amount of effort is currently directed for improving colonoscopic technology and noninvasive serological marker development. However, there is only a limited amount of data available to understand the exact mechanism of how long term chronic colitis is connected to the development of colorectal tumors. Recently, our group has identified significantly increased expression of chitinase 3-like 1 (CHI3L1) molecule in non-dysplastic mucosa from patients with IBD and remote dysplasia/cancer, compared to patients with IBD without dysplasia or healthy controls. CHI3L1 seems to contribute to the proliferation, migration, and neoplastic progression of colonic epithelial cells (CECs) under inflammatory conditions. Furthermore, the TLR4-mediated intracellular signaling cascade is likely to interact with CHI3L1 signaling in CECs. In this review article, we have concisely summarized the cellular and molecular mechanisms underlining the development of IBD and colitis-associated cancer, with particular focus on the TLR4- and CHI3L1-signaling pathways in CECs.

Keywords:

Autoimmunity, chitinase, colitis-associated cancer, mammalian inflammation, microbiota.

Affiliation:

Harvard Medical School, Massachusetts General Hospital, GRJ 825D, 55 Fruit Street, Boston, MA 02114, USA.



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