title: Role of intestinal epithelial cells in the host secretory response to infection by invasive bacteria. Bacterial entry induces epithelial prostaglandin h synthase-2 expression and prostaglandin E2 and F2alpha production.
abstract: Increased intestinal fluid secretion is a protective host response after enteric infection with invasive bacteria that is initiated within hours after infection, and is mediated by prostaglandin H synthase (PGHS) products in animal models of infection. Intestinal epithelial cells are the first host cells to become infected with invasive bacteria, which enter and pass through these cells to initiate mucosal, and ultimately systemic, infection. The present studies characterized the role of intestinal epithelial cells in the host secretory response after infection with invasive bacteria. Infection of cultured human intestinal epithelial cell lines with invasive bacteria, but not noninvasive bacteria, is shown to induce the expression of one of the rate-limiting enzymes for prostaglandin formation, PGHS-2, and the production of PGE2 and PGF2alpha. Furthermore, increased PGHS-2 expression was observed in intestinal epithelial cells in vivo after infection with invasive bacteria, using a human intestinal xenograft model in SCID mice. In support of the physiologic importance of epithelial PGHS-2 expression, supernatants from bacteria-infected intestinal epithelial cells were shown to increase chloride secretion in an in vitro model using polarized epithelial cells, and this activity was accounted for by PGE2. These studies define a novel autocrine/paracrine function of mediators produced by intestinal epithelial cells in the rapid induction of increased fluid secretion in response to intestinal infection with invasive bacteria.
authors.affiliation: Department of Medicine, University of California, San Diego, La Jolla, California 92093-0623, USA. leckmann@popmail.ucsd.edu
authors.forename: L
authors.initials: L
authors.lastname: Eckmann
authors.forename: W F
authors.initials: WF
authors.lastname: Stenson
authors.forename: T C
authors.initials: TC
authors.lastname: Savidge
authors.forename: D C
authors.initials: DC
authors.lastname: Lowe
authors.forename: K E
authors.initials: KE
authors.lastname: Barrett
authors.forename: J
authors.initials: J
authors.lastname: Fierer
authors.forename: J R
authors.initials: JR
authors.lastname: Smith
authors.forename: M F
authors.initials: MF
authors.lastname: Kagnoff
mesh_terms: D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D001419:Bacteria / Q000472:pathogenicity*; D018407:Bacterial Physiological Phenomena; D002460:Cell Line; D015237:Dinoprost / Q000096:biosynthesis* / Q000378:metabolism; D015232:Dinoprostone / Q000096:biosynthesis* / Q000378:metabolism; D004756:Enterobacteriaceae Infections / Q000378:metabolism* / Q000382:microbiology; D015971:Gene Expression Regulation, Enzymologic; D019073:HT29 Cells; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology; D007421:Intestine, Small / Q000196:embryology / Q000637:transplantation; D051379:Mice; D016513:Mice, SCID; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D012475:Salmonella / Q000502:physiology; D012481:Salmonella Infections, Animal / Q000378:metabolism / Q000382:microbiology; D014183:Transplantation, Heterologous; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism / Q000494:pharmacology
chemical_list: D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D016718:Arachidonic Acid; D015237:Dinoprost; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone