title: Anti-inflammatory properties of heat shock protein 70 and butyrate on Salmonella-induced interleukin-8 secretion in enterocyte-like Caco-2 cells.
abstract: Intestinal epithelial cells secrete the chemokine interleukin (IL)-8 in the course of inflammation. Because heat shock proteins (Hsps) and butyrate confer protection to enterocytes, we investigated whether they modulate Salmonella enterica serovar Enteritidis (S. serovar Enteritidis)-induced secretion of IL-8 in enterocyte-like Caco-2 cells. Caco-2 cells incubated with or without butyrate (0-20 m M, 48 h) were infected with S. serovar Enteritidis after (1 h at 42 degrees C, 6 h at 37 degrees C) or without prior heat shock (37 degrees C). Levels of Hsp70 production and IL-8 secretion were analysed using immunostaining of Western blots and enzyme-linked immunosorbent assay (ELISA), respectively. The cells secreted IL-8 in response to S. serovar Enteritidis and produced Hsp70 after heat shock or incubation with butyrate. The IL-8 secretion was inhibited by heat shock and butyrate concentrations as low as 0.2 m M for crypt-like and 1 m M for villous-like cells. In a dose-dependent manner, higher butyrate concentrations enhanced IL-8 secretion to maximal levels followed by a gradual but stable decline. This decline was associated with increasing production of Hsp70 and was more vivid in crypt-like cells. In addition, the higher concentrations abolished the heat shock inhibitory effect. Instead, they promoted the IL-8 production in heat-shocked cells even in the absence of S. serovar Enteritidis. We conclude that heat shock and low concentrations of butyrate inhibit IL-8 production by Caco-2 cells exposed to S. serovar Enteritidis. Higher butyrate concentrations stimulate the chemokine production and override the inhibitory effect of the heat shock. The IL-8 down-regulation could in part be mediated via production of Hsp70.
authors.affiliation: Department of Pathobiology, Division of Pathology, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands.
authors.forename: J J
authors.initials: JJ
authors.lastname: Malago
authors.forename: J F J G
authors.initials: JF
authors.lastname: Koninkx
authors.forename: P C J
authors.initials: PC
authors.lastname: Tooten
authors.forename: E A
authors.initials: EA
authors.lastname: van Liere
authors.forename: J E
authors.initials: JE
authors.lastname: van Dijk
mesh_terms: D002087:Butyrates / Q000494:pharmacology*; D018938:Caco-2 Cells; D004306:Dose-Response Relationship, Immunologic; D015536:Down-Regulation / Q000187:drug effects; D020895:Enterocytes / Q000187:drug effects / Q000276:immunology*; D018840:HSP70 Heat-Shock Proteins / Q000096:biosynthesis* / Q000276:immunology; D018869:Heat-Shock Response / Q000276:immunology; D056572:Histone Deacetylase Inhibitors; D006801:Humans; D006877:Hydroxamic Acids; D018928:Immunity, Mucosal; D016209:Interleukin-8 / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000276:immunology; D012480:Salmonella Infections / Q000276:immunology* / Q000378:metabolism; D012477:Salmonella enteritidis
chemical_list: D002087:Butyrates; D018840:HSP70 Heat-Shock Proteins; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D016209:Interleukin-8; C012589:trichostatin A