Effects of Proinflammtory Cytokines on the Expression of an Apical Bile Acid Transporter Involved in Nectrotizing Entercolitis

Abstract

Necrotizing enterocolitis (NEC) is a severe pediatric gastrointestinal disease that occurs almost exclusively in premature infants, with death rate estimated at 25% . The disease is characterized by inflammation and necrosis of the lower small intestine; however, the pathogenesis of NEC is unknown, making it an important topic for study. Previous studies have shown that during development of NEC, bile acids (compounds secreted by the liver and necessary for nutrient absorption), are increased, as well as the apical membrane transport protein, ASBT, responsible for bile acid reuptake. It is bile acid accumulation inside the cell that is believed to initiate the cellular damage observed in this disease. It has been shown that, in systems where ASBT levels are normally expressed, proinflammatory cytokines and inflammation decrease ASBT promoter activity, but it still remains to be investigated what effect inflammatory cytokines have on ASBT expression under conditions found in NEC. This project will investigate the effects, if any, that proinflammatory cytokines IL‐18 and TNF‐α have on the expression of ASBT in a neonatal rat intestinal cell line that over‐expresses ASBT. The model used will be a tetracycline‐inducible recombinant IEC‐6 cell line, to replicate elevated ASBT expression found in NEC.