The role of NF-kappaB in mediating the anti-inflammatory effects of IL-10 in intestinal epithelial cells.
In inflammatory bowel disease, cells that infiltrate the mucosa regulate intestinal epithelial cell function partly through release of pro- and anti-inflammatory cytokines. The aim of this study is to evaluate the role of the anti-inflammatory cytokine, IL-10, on normal mouse intestinal epithelial cells (Mode-K) in the absence or presence of IL-1. Western blotting assays and immunocytochemistry were used to identify the presence of IL-1 and IL-10 receptors on Mode-K cells; and electrophoretic mobility shift assays were used to study the activation of NF-kappaB transcription factor. Stimulation of Mode-K cells with IL-1 or IL-10 did not modify IL-1 and IL-10 receptor expression levels. IL-1 induced the synthesis of the enzyme cyclooxygenase-2 (COX-2) through the activation and translocation of p65 subunit of NF-kappaB. Inhibition of translocated p65 binding to DNA, inhibited COX-2 production and induced apoptosis. IL-10 inhibited IL-1-induced effects on IKB-alpha and IKB-beta proteins through stabilizing these proteins; subsequently causing inhibition of NF-kappaB translocation to the nucleus and any subsequent induction of COX-2. These data support a role for IL-10 in the regulation of IEC function under inflammatory conditions and the involvement of COX-2 in inhibiting apoptosis in mouse intestinal epithelial cells.
Al-Ashy
Randa
R
Department of Physiology, Faculty of Medicine, American University of Beirut, Beirut, Lebanon.
Chakroun
Iman
I
El-Sabban
M E
ME
Homaidan
Fadia R
FR
D000818:Animals; D002478:Cells, Cultured; D051546:Cyclooxygenase 2 / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism*; D051550:I-kappa B Kinase / Q000378:metabolism; D007249:Inflammation / Q000378:metabolism; D007375:Interleukin-1 / Q000494:pharmacology; D016753:Interleukin-10 / Q000494:pharmacology*; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000187:drug effects*; D051379:Mice; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism*; D017472:Receptors, Interleukin-1 / Q000378:metabolism; D053701:Receptors, Interleukin-10 / Q000378:metabolism
D007375:Interleukin-1; D016328:NF-kappa B; D017472:Receptors, Interleukin-1; D053701:Receptors, Interleukin-10; D016753:Interleukin-10; D051546:Cyclooxygenase 2; D051550:I-kappa B Kinase; D015232:Dinoprostone