Anti‐inflammatory properties of heat shock protein 70 and butyrate on Salmonella‐induced interleukin‐8 secretion in enterocyte‐like Caco‐2 cells

• Published in: Clinical and experimental immunology Vol. 141; no. 1; pp. 62 - 71
• Main Authors: Malago, J. J., Koninkx, J. F. J. G., Tooten, P. C. J., Van Liere, E. A., Van Dijk, J. E.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Science Ltd 01-07-2005; Blackwell; Oxford University Press; Blackwell Science Inc
• Subjects: Basic Immunology; Biological and medical sciences; butyrate; Butyrates - pharmacology; Caco-2 Cells; Dose-Response Relationship, Immunologic; Down-Regulation - drug effects; Enterocytes - drug effects; Enterocytes - immunology; Fundamental and applied biological sciences. Psychology; Fundamental immunology; heat shock; Heat-Shock Response - immunology; Histone Deacetylase Inhibitors; Hsp70; HSP70 Heat-Shock Proteins - biosynthesis; HSP70 Heat-Shock Proteins - immunology; Humans; Hydroxamic Acids; IL‐8; Immunity, Mucosal; Immunopathology; Interleukin-8 - metabolism; Intestinal Mucosa - immunology; Medical sciences; Salmonella enterica; Salmonella enteritidis; Salmonella Infections - immunology; Salmonella Infections - metabolism; Salmonella serovar Enteritidis; Shock; Salmonella enteritidis; Temperature; Angiogenic factor; Environmental factor; Butyrate; Hsp70; Immunology; Salmonella serovar Enteritidis; Heat shock protein; Bacteria; Heat shock protein 70; Salmonellosis; Interleukin 8; Enterobacteriaceae; Immunopathology; Digestive system; Secretion; Cytokine; Gut; Antiinflammatory agent; heat shock; IL-8; Infection; Heat; Bacteriosis; Enterocyte
• ISSN: 0009-9104; 1365-2249
• DOI: 10.1111/j.1365-2249.2005.02810.x

Summary
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°C, 6 h at 37°C) or without prior heat shock (37°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.