Hyperthermia-induced heat shock activates the transcription factor C/EBP-β and augments IL-6 production in human intestinal epithelial cells

Eric S. Hungness, Bruce Robb, Guang Ju Luo, Dan D. Hershko, Per Olof Hasselgren

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

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/EBP. STUDY DESIGN: Cultured Caco-2 cells, a human intestinal epithelial cell line, underwent induction of the heat shock response by hyperthermia (43°C for 1 hour). Other cells were kept at 37°C. Cells were then treated with 0.5 ng/mL human recombinant IL-1β for 4 hours. C/EBP-β and δ 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-β and δ, after which cells were subjected to hyperthermia and treatment with IL-1β. RESULTS: C/EBP-β, but not δ, 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-1β-treated cells overexpressing C/EBP-β, but not δ. CONCLUSIONS: Increased IL-6 production in IL-1β-treated enterocytes expressing the heat shock response might be caused by upregulated expression and activity of C/EBP-β. 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.

Original languageEnglish (US)
Pages (from-to)619-626
Number of pages8
JournalJournal of the American College of Surgeons
Volume195
Issue number5
DOIs
StatePublished - Nov 1 2002
Externally publishedYes

Fingerprint

Induced Hyperthermia
Heat-Shock Response
Interleukin-6
Epithelial Cells
Interleukin-1
Caco-2 Cells
Enterocytes
Mucous Membrane
Fever
CCAAT-Enhancer-Binding Proteins
Endotoxemia
DNA
Electrophoretic Mobility Shift Assay
heat shock transcription factor
Interleukin-4
Cultured Cells
Shock
Sepsis
Plasmids
Anti-Inflammatory Agents

ASJC Scopus subject areas

  • Surgery

Cite this

Hyperthermia-induced heat shock activates the transcription factor C/EBP-β and augments IL-6 production in human intestinal epithelial cells. / Hungness, Eric S.; Robb, Bruce; Luo, Guang Ju; Hershko, Dan D.; Hasselgren, Per Olof.

In: Journal of the American College of Surgeons, Vol. 195, No. 5, 01.11.2002, p. 619-626.

Research output: Contribution to journalArticle

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abstract = "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/EBP. STUDY DESIGN: Cultured Caco-2 cells, a human intestinal epithelial cell line, underwent induction of the heat shock response by hyperthermia (43°C for 1 hour). Other cells were kept at 37°C. Cells were then treated with 0.5 ng/mL human recombinant IL-1β for 4 hours. C/EBP-β and δ 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-β and δ, after which cells were subjected to hyperthermia and treatment with IL-1β. RESULTS: C/EBP-β, but not δ, 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-1β-treated cells overexpressing C/EBP-β, but not δ. CONCLUSIONS: Increased IL-6 production in IL-1β-treated enterocytes expressing the heat shock response might be caused by upregulated expression and activity of C/EBP-β. 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.",
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AU - Hershko, Dan D.

AU - Hasselgren, Per Olof

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N2 - 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/EBP. STUDY DESIGN: Cultured Caco-2 cells, a human intestinal epithelial cell line, underwent induction of the heat shock response by hyperthermia (43°C for 1 hour). Other cells were kept at 37°C. Cells were then treated with 0.5 ng/mL human recombinant IL-1β for 4 hours. C/EBP-β and δ 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-β and δ, after which cells were subjected to hyperthermia and treatment with IL-1β. RESULTS: C/EBP-β, but not δ, 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-1β-treated cells overexpressing C/EBP-β, but not δ. CONCLUSIONS: Increased IL-6 production in IL-1β-treated enterocytes expressing the heat shock response might be caused by upregulated expression and activity of C/EBP-β. 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.

AB - 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/EBP. STUDY DESIGN: Cultured Caco-2 cells, a human intestinal epithelial cell line, underwent induction of the heat shock response by hyperthermia (43°C for 1 hour). Other cells were kept at 37°C. Cells were then treated with 0.5 ng/mL human recombinant IL-1β for 4 hours. C/EBP-β and δ 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-β and δ, after which cells were subjected to hyperthermia and treatment with IL-1β. RESULTS: C/EBP-β, but not δ, 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-1β-treated cells overexpressing C/EBP-β, but not δ. CONCLUSIONS: Increased IL-6 production in IL-1β-treated enterocytes expressing the heat shock response might be caused by upregulated expression and activity of C/EBP-β. 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.

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