Regulation of nuclear factor-kappaB in intestinal epithelial cells in a cell model of inflammation.
BACKGROUND
Interleukin-1 (IL-1), an inflammatory cytokine whose levels are elevated in inflamed mucosa, causes part of its effect on intestinal epithelial cells (IEC) through inducing ceramide production.


OBJECTIVE
To study the role of nuclear factor-kappaB (NF-kappaB), a pro-inflammatory and anti-apoptotic factor, in IL-1-treated IEC.


METHODS
NF-kappaB activity and levels of apoptotic proteins were assessed by electrophoretic mobility shift assay and RNA-protection assay, respectively.


RESULTS
IL-1 and ceramide, which have been shown to partially mediate IL-1 effects on IEC, activated NF-kappaB levels significantly. This activation was due to a decrease in IkappaB-alpha and IkappaB-beta protein levels. Moreover, the ratio of mRNA levels of anti-apoptotic to pro-apoptotic proteins was significantly increased in IL-1-treated IEC.


CONCLUSIONS
NF-kappaB may play a key role in the regulation of the expression of pro-inflammatory and/or apoptotic genes in inflammatory bowel disease, making this protein an attractive target for therapeutic intervention.
Homaidan
Fadia R
FR
Department of Physiology, American University of Beirut, Faculty of Medicine, Beirut, Lebanon. fh01@aub.edu.lb
Chakroun
Iman
I
El-Sabban
Marwan E
ME
D000818:Animals; D017209:Apoptosis / Q000276:immunology; D051017:Apoptosis Regulatory Proteins; D002460:Cell Line; D002518:Ceramides / Q000494:pharmacology; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D004751:Enteritis / Q000378:metabolism* / Q000473:pathology; D004847:Epithelial Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D020672:I-kappa B Proteins / Q000378:metabolism; D007375:Interleukin-1 / Q000494:pharmacology; D007413:Intestinal Mucosa / Q000166:cytology* / Q000276:immunology*; D007976:Leupeptins / Q000494:pharmacology; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism*; D011506:Proteins / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D051020:bcl-X Protein
D051017:Apoptosis Regulatory Proteins; C491073:BCL2L2 protein, human; D002518:Ceramides; D015853:Cysteine Proteinase Inhibitors; C083487:I kappa B beta protein; D020672:I-kappa B Proteins; D007375:Interleukin-1; D007976:Leupeptins; D016328:NF-kappa B; C000606204:NFKBIA protein, human; C105627:NFKBIE protein, human; C000606205:Nfkbia protein, mouse; C491366:Nfkbie protein, mouse; D011506:Proteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D051020:bcl-X Protein; D000072000:NF-KappaB Inhibitor alpha; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde