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

J J Malago, J F J G Koninkx, P C J Tooten, E A van Liere, J E van Dijk

    Research output: Contribution to journalArticleAcademicpeer-review


    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.

    Original languageEnglish
    Pages (from-to)62-71
    Number of pages10
    JournalClinical and Experimental Immunology
    Issue number1
    Publication statusPublished - Jul 2005


    • Butyrates
    • Caco-2 Cells
    • Dose-Response Relationship, Immunologic
    • Down-Regulation
    • Enterocytes
    • HSP70 Heat-Shock Proteins
    • Heat-Shock Response
    • Histone Deacetylase Inhibitors
    • Humans
    • Hydroxamic Acids
    • Immunity, Mucosal
    • Interleukin-8
    • Intestinal Mucosa
    • Salmonella Infections
    • Salmonella enteritidis


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