Toll-Like Receptor 4 Signaling Integrates Intestinal Inflammation with Tumorigenesis: Lessons from the Murine Model of Colitis-Associated Cancer

Cancers

Yasmin Hernandez¹  John Sotolongo¹ 

[1] Department of Medicine, Division of Gastroenterology, University of Miami Miller School of Medicine, Miami, Florida 33101, USA;

关键词: colitis;    colitis-associated cancer;    bacteria;    toll-like receptor;    prostaglandin;    inflammation;    innate immunity;   

DOI  :  10.3390/cancers3033104

来源: mdpi

【 摘 要 】

Chronic inflammation has long been implicated as a predisposition for cancer, but the underlying mechanism for how this occurs has remained obscure. Ulcerative colitis (UC) is a chronic inflammatory disorder of the large intestine which is known to be highly linked to colorectal cancer. During chronic inflammation the intestinal mucosa is in a constant cycle of injury and repair resulting in aberrant epithelial proliferation, a process that increases the risk of neoplastic transformation. In particular, the coexistence of commensal flora in the intestine plays an important role in the regulation of mucosal restitution after epithelial injury. It has become apparent that signaling through toll-like receptors (TLRs), the receptor family recognizing pathogen-associated molecular patterns, is crucial to intestinal epithelial proliferation and mucosal restitution. We have recently described two important downstream pathways underlying TLR4-mediated epithelial proliferation in a mouse model of colitis-associated cancer; i.e., cyclooxygenase 2 (COX-2)-mediated production of prostaglandin E₂ (PGE₂), and induction of specific ligands for epidermal growth factor receptor (EGFR). These two pathways are closely involved with mucosal levels of PGE₂ and other prostanoids such as 15-deoxy-delta 12,14-prostaglandin-J2 (15d-PGJ2). Understanding the fine interplay between the TLR signaling and intestinal tumorigenesis in the setting of chronic inflammation can contribute to establishing a novel treatment strategy for inflammation-associated cancers.

【 授权许可】

CC BY   
© 2011 by the authors; licensee MDPI, Basel, Switzerland.