Interleukin-8 in gastrointestinal inflammation and malignancy: induction and clinical consequences

Abstract

Interleukin-8 in gastrointestinal inflammation and malignancy: induction and clinical consequences James A Cotton,1 Jaye M Platnich,1 Daniel A Muruve,1 Humberto B Jijon,1 Andre G Buret,2 Paul L Beck,1 1Department of Medicine, 2Department of Biological Sciences, University of Calgary, Calgary, AB, Canada Abstract: Owing to its immense surface area, the mucosal surface of the gastrointestinal (GI) tract is continually subject to numerous endogenous and exogenous antigens capable of inducing an inflammatory response in the appropriate setting. In certain individuals, these inflammatory responses may also become dysregulated and result in the development of chronic GI inflammation, such as inflammatory bowel disease. Furthermore, gastric and colonic malignant processes are extremely common and, to date, still have high mortality rates. As a result, continuing research has focused on elucidating potential molecular mechanisms involved in these processes in an attempt to understand the pathophysiology of these diseases and, potentially, aid in the development of novel therapeutics. Interleukin-8 (CXCL8) is a small molecular weight chemokine identified almost 30 years ago. Ongoing research has demonstrated that this factor contributes to a multitude of pathophysiological processes within the GI tract, including chronic GI inflammatory states, such as inflammatory bowel disease, and gastric and colonic carcinomas. This review highlights the role of CXCL8 in GI inflammation and malignancy. It describes molecular mechanisms involved in promoting and restraining CXCL8 production in GI cells and how CXCL8 contributes to the pathophysiology of a variety of GI inflammatory processes. Finally, this review describes a variety of mechanisms by which CXCL8–CXCL1/2 signaling may contribute to GI malignancy. Keywords: CXCL8, inflammatory bowel disease, IBD, colon cancer, IL-8, Crohn’s disease, ulcerative colitis