Transcription factors C/EBP-β and -δ regulate IL-6 production in IL-1β-stimulated human enterocytes

✍ Scribed by Eric S. Hungness; Guang-ju Luo; Timothy A. Pritts; Xiaoyan Sun; Bruce W. Robb; Dan Hershko; Per-Olof Hasselgren

• Publisher: John Wiley and Sons
• Year: 2002
• Tongue: English
• Weight: 141 KB
• Volume: 192
• Category: Article
• ISSN: 0021-9541
• DOI: 10.1002/jcp.10116

✦ Synopsis

Abstract

In recent studies, treatment with IL‐1β of cultured Caco‐2 cells, a human intestinal epithelial cell line, resulted in transcriptional upregulation of IL‐6 production. The role of C/EBP‐β and ‐δ in enterocyte IL‐6 production is not known. Stimulation with IL‐1β 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‐1β 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‐1β 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‐β and ‐δ in IL‐1β‐treated Caco‐2 cells resulted in a 10–12‐fold increase in IL‐6 production. The results suggest that the β and δ isoforms of the C/EBP family of transcription factors at least in part regulate IL‐6 production in human intestinal epithelial cells. © 2002 Wiley‐Liss, Inc.