title: Bacterial superantigen-treated intestinal epithelial cells upregulate heat shock proteins 25 and 72 and are resistant to oxidant cytotoxicity.
abstract: While the pathological events evoked by infection are commonly described, effective host responses to bacteria and their products should primarily be protective. Heat shock protein (Hsp) expression is upregulated by many stimuli and serves to maintain intracellular protein integrity. The ability of the prototypic superantigen, Staphylococcus aureus enterotoxin B (SEB) to induce Hsps was investigated with BALB/c mice and by in vitro addition to the murine small intestinal epithelial cell line MSIE. SEB-treated (5 or 100 microg intraperitoneally) mice revealed increased Hsp25 and Hsp72, but not Hsc73, in jejunal lymphocytes and epithelial cells. A similar Hsp response to SEB occurred in MSIE cells and was preceded by activation of the ERK1/2 and p38 mitogen-activated protein kinases but not the SAPK/JNK pathway; pharmacological inhibition of ERK1/2, but not p38, significantly reduced SEB-induced Hsps. Moreover, SEB-treated MSIE cells were protected against oxidant-induced cytotoxicity (measured by 51Cr release) and F-actin depolymerization. Thus, SEB exposure results in a rapid induction of the Hsp25 and Hsp72 in intestinal epithelial cells, both directly and through lymphocyte activation, and we suggest that this event is important in protecting the gut from damage by Staphylococcus infection or in the reparatory process and may be a generalized response to lumen-derived bacterial toxins.
authors.affiliation: The Inflammatory Bowel Disease Research Center, Department of Medicine, The University of Chicago, Chicago, Illinois 60637, USA.
authors.forename: Mark W
authors.initials: MW
authors.lastname: Musch
authors.forename: Elaine O
authors.initials: EO
authors.lastname: Petrof
authors.forename: Keishi
authors.initials: K
authors.lastname: Kojima
authors.forename: Hongyu
authors.initials: H
authors.lastname: Ren
authors.forename: Derek M
authors.initials: DM
authors.lastname: McKay
authors.forename: Eugene B
authors.initials: EB
authors.lastname: Chang
mesh_terms: D000818:Animals; D002460:Cell Line; D002700:Chloramines / Q000633:toxicity; D004768:Enterotoxins / Q000276:immunology / Q000494:pharmacology*; D004847:Epithelial Cells / Q000187:drug effects / Q000276:immunology; D050884:HSP72 Heat-Shock Proteins; D006360:Heat-Shock Proteins / Q000378:metabolism*; D007421:Intestine, Small / Q000166:cytology / Q000187:drug effects*; D007583:Jejunum / Q000166:cytology / Q000276:immunology; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018832:Molecular Chaperones; D009363:Neoplasm Proteins / Q000378:metabolism*; D016877:Oxidants / Q000633:toxicity; D013211:Staphylococcus aureus / Q000276:immunology; D018089:Superantigens / Q000276:immunology / Q000494:pharmacology*; D015854:Up-Regulation
chemical_list: D002700:Chloramines; D004768:Enterotoxins; D050884:HSP72 Heat-Shock Proteins; D006360:Heat-Shock Proteins; C486113:Hsbp1 protein, mouse; D018832:Molecular Chaperones; D009363:Neoplasm Proteins; D016877:Oxidants; D018089:Superantigens; C031818:enterotoxin B, staphylococcal