title: Luminal bacterial flora determines physiological expression of intestinal epithelial cytoprotective heat shock proteins 25 and 72.
abstract: Heat shock proteins (HSP) 25 and 72 are expressed normally by surface colonocytes but not by small intestinal enterocytes. We hypothesized that luminal commensal microflora maintain the observed colonocyte HSP expression. The ability of the small intestine to respond to bacteria and their products and modulate HSPs has not been determined. The effects of luminal bacterial flora in surgically created midjejunal self-filling (SFL) vs. self-emptying (SEL) small-bowel blind loops on epithelial HSP expression were studied. HSP25 and HSP72 expression were assessed by immunoblot and immunohistochemistry. SFL were chronically colonized, whereas SEL contained levels of bacteria normal for the proximal small intestine. SFL creation significantly increased HSP25 and HSP72 expression relative to corresponding sections from SEL. Metronidazole treatment, which primarily affects anaerobic bacteria as well as a diet lacking fermentable fiber, significantly decreased SFL HSP expression. Small bowel incubation with butyrate ex vivo induced a sustained and significant upregulation of HSP25 and altered HSP72 expression, confirming the role of short-chain fatty acids. To determine whether HSPs induction altered responses to an injury, effects of the oxidant, monochloramine, on epithelial resistance and short-circuit current (I(sc)) responses to carbachol and glucose were compared. Increased SFL HSP expression was associated with protection against oxidant-induced decreases in transmural resistance and I(sc) responses to glucose, but not secretory responses to carbachol. In conclusion, luminal microflora and their metabolic byproducts direct expression of HSPs in gut epithelial cells, an effect that contributes to preservation of epithelial cell viability under conditions of stress.
authors.affiliation: Martin Boyer Professor of Medicine, The Univ. of Chicago, 5841 S. Maryland Ave. Rm. G705, MC 6084, Chicago, IL, 60637, USA.
authors.forename: Donna L
authors.initials: DL
authors.lastname: Arvans
authors.forename: Stephan R
authors.initials: SR
authors.lastname: Vavricka
authors.forename: Hongyu
authors.initials: H
authors.lastname: Ren
authors.forename: Mark W
authors.initials: MW
authors.lastname: Musch
authors.forename: Lisa
authors.initials: L
authors.lastname: Kang
authors.forename: Flavio G
authors.initials: FG
authors.lastname: Rocha
authors.forename: Alvaro
authors.initials: A
authors.lastname: Lucioni
authors.forename: Jerrold R
authors.initials: JR
authors.lastname: Turner
authors.forename: John
authors.initials: J
authors.lastname: Alverdy
authors.forename: Eugene B
authors.initials: EB
authors.lastname: Chang
mesh_terms: D000818:Animals; D018407:Bacterial Physiological Phenomena; D001692:Biological Transport / Q000187:drug effects; D002087:Butyrates / Q000494:pharmacology; D002700:Chloramines / Q000494:pharmacology; D019610:Cytoprotection; D004043:Dietary Fiber / Q000494:pharmacology; D005232:Fatty Acids, Volatile / Q000378:metabolism; D005285:Fermentation; D005766:Gastrointestinal Contents; D041981:Gastrointestinal Tract / Q000378:metabolism; D055551:HSP27 Heat-Shock Proteins; D050884:HSP72 Heat-Shock Proteins; D006360:Heat-Shock Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000382:microbiology*; D007421:Intestine, Small / Q000382:microbiology*; D007583:Jejunum / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D016877:Oxidants / Q000494:pharmacology; D010539:Permeability / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution
chemical_list: D002087:Butyrates; D002700:Chloramines; D004043:Dietary Fiber; D005232:Fatty Acids, Volatile; D055551:HSP27 Heat-Shock Proteins; D050884:HSP72 Heat-Shock Proteins; D006360:Heat-Shock Proteins; C486114:Hspb1 protein, rat; D009363:Neoplasm Proteins; D016877:Oxidants; C030816:chloramine