title: IL-1beta activates C/EBP-beta and delta in human enterocytes through a mitogen-activated protein kinase signaling pathway.
abstract: The enterocyte is an active participant in the inflammatory and metabolic response to sepsis, endotoxemia and other critical illnesses and is the site for cytokine and acute phase protein production in these conditions. The role of the CCAAT/enhancer binding protein (C/EBP) family of transcription factors in the response to inflammatory stimuli in the enterocyte is not well understood. In the present study, we treated Caco-2 cells with IL-1beta and determined C/EBP DNA binding activity by electrophoretic mobility shift assay. The involvement of the alpha, beta, and delta isoforms was determined by supershift analysis and Western blot analysis of proteins from the nuclear fraction. The role of the mitogen-activated protein kinase (MAPK) signaling pathway was assessed by treating cells with the MAPK inhibitor PD-98059. Treatment of the Caco-2 cells with IL-1beta resulted in increased CCAAT/enhancer binding protein DNA binding activity. Supershift analysis and Western blotting indicated that this response to IL-1beta mainly reflected the delta isoform, and to a lesser degree the beta isoform. Treatment of the cells with PD-98059 inhibited the IL-1beta-induced increase in beta and delta activity. The results suggest that members of the CCAAT/enhancer binding protein family of transcription factors are activated in enterocytes during inflammatory conditions characterized by high levels of IL-1beta.
authors.affiliation: Department of Surgery, University of Cincinnati, 231 Bethesda Avenue, Mail Location 0558, Cincinnati, OH 45267-0558, USA.
authors.forename: Eric S
authors.initials: ES
authors.lastname: Hungness
authors.forename: Timothy A
authors.initials: TA
authors.lastname: Pritts
authors.forename: Guang Ju
authors.initials: GJ
authors.lastname: Luo
authors.forename: Dan D
authors.initials: DD
authors.lastname: Hershko
authors.forename: Bruce W
authors.initials: BW
authors.lastname: Robb
authors.forename: Per Olof
authors.initials: PO
authors.lastname: Hasselgren
mesh_terms: D022782:CCAAT-Enhancer-Binding Protein-beta / Q000235:genetics / Q000378:metabolism*; D051743:CCAAT-Enhancer-Binding Protein-delta; D022762:CCAAT-Enhancer-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D018938:Caco-2 Cells; D002467:Cell Nucleus / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D015536:Down-Regulation; D020895:Enterocytes / Q000187:drug effects / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011485:Protein Binding; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors; D015854:Up-Regulation
chemical_list: D022782:CCAAT-Enhancer-Binding Protein-beta; D022762:CCAAT-Enhancer-Binding Proteins; C497252:CEBPD protein, human; D004791:Enzyme Inhibitors; D005419:Flavonoids; D007375:Interleukin-1; D020033:Protein Isoforms; D014157:Transcription Factors; D051743:CCAAT-Enhancer-Binding Protein-delta; D004247:DNA; D020928:Mitogen-Activated Protein Kinases; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one