Title: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
Volume: 13
Issue: 7
Author(s): A. Kamba, I.-A. Lee and E. Mizoguchi
Affiliation:
Keywords:
Autoimmunity, chitinase, colitis-associated cancer, mammalian inflammation, microbiota.
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.
