Grant: Operating Grant

The enormous mucosal surface of gastrointestinal (GI) tract is continuously exposed to a large numbers of food and water-borne microbes and toxic stimuli and is clearly more susceptible to inflammation than any other organ in the body. However, despite this challenge, the gut is rarely overwhelmed by microbial pathogens, suggesting that the GI tract has effective defense system. GI tract contains the largest endocrine organ in the body, and interactions among immune, endocrine and nervous systems are considered to comprise an integrated network of host defense in gut. Hundreds of thousands of endocrine cells are present throughout the GI tract and react to changes in gut contents by releasing hormones. The best characterized subset of enteric endocrine cells is enterochromaffin (EC) cells, which synthesize and release serotonin (5-hydroxytryptamine, 5-HT). 5-HT contributes to gut physiology and is considered to be important in maintaining the integrity of gut. 5-HT has been implicated in a number of diseases including functional disorders like irritable bowel syndrome (IBS), inflammatory bowel disease (IBD), and in a number of GI infections. The association between alteration in 5-HT production and various GI diseases highly emphasizes the significance of 5-HT in intestinal pathophysiology. However, the mechanisms regulating the changes in EC cells/5-HT content during infection and inflammation, or the precise role of 5-HT in gut pathology and host defense is still not clear. This research proposal examines the mechanisms by which immune system regulate turnover of EC cells and 5-HT production and the role of 5-HT in gut pathology and host defense in enteric infection. Understanding the role of 5-HT in gut pathology and host defense will provide new insights into the mechanisms of gut function which may ultimately lead to improved therapeutic strategies in GI functional and inflammatory disorders.