Scott E. Plevy, MD
Photo: Scott E. Plevy



Elected 2007
My laboratory studies how interactions between the immune system and the environment lead to the initiation and perpetuation of inflammation in inflammatory bowel disease (IBD). To address these questions, we utilize mouse models of IBD, as well as cells and tissue from IBD patients. The environmental factor that has attracted the most attention in the pathogenesis of IBD is the enteric microbial flora. Our laboratory is actively involved in many studies to determine at the molecular level how bacteria activate innate immune responses in the mucosal immune system. In particular, we have focused on the expression of interleukin (IL)-12 family members as central events in chronic inflammation. Understanding how bacteria activate pro-inflammatory pathways in the intestine, and understanding mechanisms through which these pathways can be inhibited, will lead to new insights into the pathogenesis of IBD, and will reveal new therapeutic targets. We are also interested in a second environmental factor that profoundly influences the course of IBD. It is well described in studies from numerous geographic populations that cigarette smoking is protective against the development of ulcerative colitis (UC). We have been studying the potent anti-inflammatory effects of a component of cigarette smoke, carbon monoxide (CO), in mouse models of IBD. Low level CO exposure in IL-10 deficient mice ameliorated chronic intestinal inflammation through a novel pathway that involves upregulation of the enzyme heme oxygenase-1 (HO-1). Further work in the laboratory focuses on molecular mechanisms through which CO and HO-1 exert anti-inflammatory effects.