The role of p38 mitogen-activated protein kinase in the pathogenesis of inflammatory bowel disease

Abstract

Inflammatory bowel disease (IBD) includes ulcerative colitis and Crohn's disease which is characterized by the recurrent intestinal inflammation and overactive immune responses. The signaling pathways of p38 mitogen-activated protein kinase (MAPK) play an important role in bowel inflammation. The inhibition of p38 MAPK can effectively suppress the expression of inflammatory mediators. However, due to the obvious preclinical and clinical side effects, p38 inhibitors are unacceptable in safety profiles and cannot be applied in the treatment of IBD. MAPK-activated protein kinase 2 (MK2), as the direct substrate of p38α and p38β, is a multifunctional signaling protein in the progression of inflammation and several lines of evidence demonstrate that the inhibition of MK2 may produce the same beneficial effect as the inhibition of p38 MAPK. Hence, MK2 is likely to be a potential drug target for the treatment of IBD. © 2011 The Authors. Journal of Digestive Diseases © 2011 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and Blackwell Publishing Asia Pty Ltd.