ROLE OF INTESTINAL EPITHELIAL-CELLS IN THE HOST SECRETORY RESPONSE TOINFECTION BY INVASIVE BACTERIA - BACTERIAL ENTRY INDUCES EPITHELIAL PROSTAGLANDIN-H SYNTHASE-2 EXPRESSION AND PROSTAGLANDIN E-2 AND F2-ALPHA PRODUCTION

Increased intestinal fluid secretion is a protective host response aft er enteric infection with invasive bacteria that is initiated within h ours after infection, and is mediated by prostaglandin H synthase (PGH S) products in animal models of infection. Intestinal epithelial cells are the first host cells to become infected with invasive bacteria, w hich enter and pass through these cells to initiate mucosal, and ultim ately systemic, infection. The present studies characterized the role of intestinal epithelial cells in the host secretory response after in fection with invasive bacteria. Infection of cultured human intestinal epithelial cell lines with invasive bacteria, but not noninvasive bac teria, is shown to induce the expression of one of the rate-limiting e nzymes for prostaglandin formation, PGHS-2, and the production of PGE( 2) and PGF(2 alpha). Furthermore, increased PGHS-2 expression was obse rved in intestinal epithelial cells in vivo after infection with invas ive bacteria, using a human intestinal xenograft model in SCID mice. I n support of the physiologic importance of epithelial PGHS-2 expressio n, supernatants from bacteria-infected intestinal epithelial cells wer e shown to increase chloride secretion in an in vitro model using pola rized epithelial cells, and this activity was accounted for by PGE(2). These studies define a novel autocrine/paracrine function of mediator s produced by intestinal epithelial cells in the rapid induction of in creased fluid secretion in response to intestinal infection with invas ive bacteria.