Hyperthermia-induced heat shock activates the transcription factor c/EBP-beta and augments IL-6 production in human intestinal epithelial cells.
BACKGROUND
Interleukin (IL)-6 production is increased in gut mucosa during sepsis and endotoxemia. The heat shock response augments IL-6 production under these conditions, but the mechanism is not known. We hypothesized that heat shock stimulates IL-6 production in enterocytes by increasing expression and activity of the transcription factor C/EBB.


METHODS
Cultured Caco-2 cells, a human intestinal epithelial cell line, underwent induction of the heat shock response by hyperthermia (43 degrees C for 1 hour). Other cells were kept at 37 degrees C. Cells were then treated with 0.5 ng/mL human recombinant IL-1beta for 4 hours. C/EBP-beta and delta DNA binding activity was determined by electrophoretic mobility shift assay and supershift analysis. In additional experiments, Caco-2 cells were transfected with expression plasmids for C/EBP-beta and delta, after which cells were subjected to hyperthermia and treatment with IL-1beta.


RESULTS
C/EBP-beta, but not delta, protein levels and DNA binding activity were increased in Caco-2 cells expressing the heat shock response. Induction of the heat shock response augmented IL-6 production in IL-1beta-treated cells overexpressing C/EBP-beta, but not delta.


CONCLUSIONS
Increased IL-6 production in IL-1beta-treated enterocytes expressing the heat shock response might be caused by upregulated expression and activity of CIEBP-beta. Because recent studies suggest that IL-6 might be an antiinflammatory cytokine and might exert protective effects in gut mucosa and enterocytes, understanding mechanisms by which the heat shock response augments IL-6 production might have important clinical implications.
Hungness
Eric S
ES
Department of Surgery, University of Cincinnati, OH, USA.
Robb
Bruce W
BW
Luo
Guang-Ju
GJ
Hershko
Dan D
DD
Hasselgren
Per-Olof
PO
D022762:CCAAT-Enhancer-Binding Proteins / Q000276:immunology*; D018938:Caco-2 Cells; D020895:Enterocytes / Q000276:immunology*; D018869:Heat-Shock Response / Q000276:immunology*; D006801:Humans; D006979:Hyperthermia, Induced; D007375:Interleukin-1 / Q000276:immunology*; D015850:Interleukin-6 / Q000276:immunology*; D051742:Transcription Factor CHOP; D014157:Transcription Factors / Q000276:immunology*; D014162:Transfection; D015854:Up-Regulation / Q000276:immunology
D022762:CCAAT-Enhancer-Binding Proteins; C497249:DDIT3 protein, human; D007375:Interleukin-1; D015850:Interleukin-6; D014157:Transcription Factors; D051742:Transcription Factor CHOP