Journal
JOURNAL OF CELLULAR BIOCHEMISTRY
Volume 91, Issue 5, Pages 951-961Publisher
WILEY
DOI: 10.1002/jcb.20014
Keywords
enterocytes; cytokines; protein synthesis inhibitors; cell signaling; transcription factors
Categories
Funding
- NIDDK NIH HHS [R01 DK60546] Funding Source: Medline
Ask authors/readers for more resources
Protein synthesis inhibitors paradoxically increase the expression of early-gene products, including various cytokines, through a process known as superinduction. Superinduction is cell-specific and the mechanisms involved are not fully understood but are usually attributed to decreased mRNA degradation. There is, however, increasing evidence that activation of signaling cascades and increased transcriptional activation may be involved as well. Recent studies suggest that IL-6 production in the intestinal mucosa is particularly important due to its anti-inflammatory and protective effects. The effect of protein synthesis inhibitors on IL-6 production in enterocytes, however, is unknown. Treatment of Caco-2 cells with cycloheximide (10 mug/ml) increased IL-6 mRNA and protein levels in IL-1beta-treated cells and this was associated with increased mRNA stabilization. In addition, cycloheximide suppressed IkappaBalpha resynthesis and prolonged p38MAP kinase activation and these changes were associated with sustained activation of the transcription factor NF-kappaB. NF-kappaB activation, in turn, was prevented by the specific p38MAP kinase inhibitor SB208350. Our results suggest that superinduction of IL-6 by cycloheximide in enterocytes results from both increased mRNA stabilization and upregulated transcriptional activity mediated by prolonged activation of the p38 MAP kinase and NF-kappaB. (C) 2004 Wiley-Liss, Inc.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available