Transcription factors C/EBP-beta and -delta regulate IL-6 production in IL-1beta-stimulated human enterocytes.
In recent studies, treatment with IL-1beta of cultured Caco-2 cells, a human intestinal epithelial cell line, resulted in transcriptional upregulation of IL-6 production. The role of C/EBP-beta and -delta in enterocyte IL-6 production is not known. Stimulation with IL-1beta of Caco-2 cells transiently transfected with a luciferase reporter plasmid containing a wild-type IL-6 promoter resulted in an approximately 3.5-fold increase in luciferase activity. This effect of IL-1beta was reduced by approximately 30% when the C/EBP binding site in the IL-6 promoter was mutated, supporting a role of C/EBP in the regulation of IL-6 production. When Caco-2 cells were treated with IL-1beta in the presence of the MAPK inhibitor, PD-98059, IL-6 mRNA and protein levels were reduced by the same concentrations of PD-98059 that inhibited C/EBP DNA binding activity in previous studies. Finally, overexpression of C/EBP-beta and -delta in IL-1beta-treated Caco-2 cells resulted in a 10-12-fold increase in IL-6 production. The results suggest that the beta and delta isoforms of the C/EBP family of transcription factors at least in part regulate IL-6 production in human intestinal epithelial cells.
Department of Surgery, University of Cincinnati, Cincinnati, Ohio 45267-0558, USA.
Eric S
ES
Hungness
Guang-Ju
GJ
Luo
Timothy A
TA
Pritts
Xiaoyan
X
Sun
Bruce W
BW
Robb
Dan
D
Hershko
Per-Olof
PO
Hasselgren
D022782:CCAAT-Enhancer-Binding Protein-beta / Q000502:physiology*; D051743:CCAAT-Enhancer-Binding Protein-delta; D022762:CCAAT-Enhancer-Binding Proteins / Q000502:physiology*; D018938:Caco-2 Cells; D020895:Enterocytes / Q000187:drug effects* / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D015850:Interleukin-6 / Q000096:biosynthesis* / Q000235:genetics; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors; D009154:Mutation; D011401:Promoter Regions, Genetic / Q000235:genetics; D012333:RNA, Messenger / Q000037:antagonists & inhibitors; D014157:Transcription Factors; D000093242:Interleukin-6 Inhibitors
D022782:CCAAT-Enhancer-Binding Protein-beta; D051743:CCAAT-Enhancer-Binding Protein-delta; D022762:CCAAT-Enhancer-Binding Proteins; D004791:Enzyme Inhibitors; D005419:Flavonoids; D007375:Interleukin-1; D015850:Interleukin-6; D020928:Mitogen-Activated Protein Kinases; D012333:RNA, Messenger; D014157:Transcription Factors; D000093242:Interleukin-6 Inhibitors; C497252:CEBPD protein, human; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one