This proposal aims to characterize the role of the Rho family of GTP- binding proteins in bacterial-induced chemoattractant release from polarized epithelial cells. Currently very little is known about the signal transduction pathway responsible for eliciting an immune response to pathogenic bacterial invasion of intestinal epithelium. Recent evidence suggests that proteins of the type III secretion apparatus interact with members of the Rho family and are responsible for membrane ruffling on non-polarized cells. Intestinal inflammation is characterized by epithelial orchestration of PMN movement and the subsequent effects of the recruited PMN on epithelial function. This proposal will also examine the role of the Rho family of proteins on the transepithelial migration of PMN. It will also seek to identify and characterize the PMN receptor for the recently identified apical chemoattractant, pathogen-elicited epithelial chemoattractant (PEEC). Additionally, the mechanism by which the PEEC is desensitized and desensitizes (cross-desensitization) other chemokine receptors will be explored.
| Hobert, Michael E; Sands, Kara A; Mrsny, Randal J et al. (2002) Cdc42 and Rac1 regulate late events in Salmonella typhimurium-induced interleukin-8 secretion from polarized epithelial cells. J Biol Chem 277:51025-32 |
| Reed, Katharine A; Hobert, Michael E; Kolenda, Claire E et al. (2002) The Salmonella typhimurium flagellar basal body protein FliE is required for flagellin production and to induce a proinflammatory response in epithelial cells. J Biol Chem 277:13346-53 |
