PROSTaGLaNDIN E2 SIGNaLING THROUGH THE EP4 RECEPTOR aLTERS HUMaN COLONIC EPITHELIaL BaRRIER FUNCTION

摘要

Prostaglandin E2 (PGE_2) is one of the important pro inflammatory molecules found in the gut and is produced in excess towards an inflammatory insult. In acute gastrointestinal inflammation, high output: PGE_2 levels are a hallmark of inflammatory bowel diseases and entero-invasive bacterial/parasitic diseases. The mechanism(s) whereby PGE_2 alter epithelial barrier function is not known. In this study, we investigated whether PGE_2 plays a role in disrupting epithelial barrier function through alteration of plasma membrane ion channels and tight junctions (TJV Monolayers of T84 human colonic epithelial cells treated with PGE] showed a concentration (8nM-lpM) and time-dependent precipitous decrease (5 minutes) in Trans Epithelial Resistance (TER) indicating a loss of epithelial cell integrity. Using highly specific inhibitors we derermined that both CFTR and Na+C1K co transporters were responsible tor the transcellular mode of decrease in TER.