Interleukin-1beta and tumor necrosis factor-alpha upregulate interleukin-23 subunit p19 gene expression in human colonic subepithelial myofibroblasts.
The recently identified cytokine interleukin-23 (IL-23) consists of p19 and p40 subunits. The major cellular source of IL-23 is dendritic cells and/or macrophages. We investigated the expression of IL-23 p19 mRNA in human colonic subepithelial myofibroblasts (SEMFs). p19 mRNA was not expressed in unstimulated SEMFs, but IL-1beta and TNF-alpha strongly induced p19 mRNA expression in these cells. The effects of IL-1beta were much stronger than those of TNF-alpha. These responses were observed in both a dose- and time-dependent manner. Furthermore, these cytokines acted synergistically when used in combination. A blockade of NF-kappaB activation by the overexpression of a stable form of IkappaBalpha completely blocked these responses, indicating that the induction of p19 mRNA expression by IL-1beta and TNF-alpha was mediated by the NF-kappaB activation pathway. In conclusion, this is the first report demonstrating that IL-23 p19 mRNA is inducible in colonic myofibroblasts by IL-1beta and TNF-alpha. The p19 expression in these cells might play a role in mucosal immune responses.
Zhang
Zhuobin
Z
Department of Internal Medicine, Shiga University of Medical Science, Seta-Tukinowa, Otsu 520-2192, Japan.
Andoh
Akira
A
Yasui
Hirofumi
H
Inatomi
Osamu
O
Hata
Kazunori
K
Tsujikawa
Tomoyuki
T
Kitoh
Katsuyuki
K
Takayanagi
Atsushi
A
Shimizu
Nobuyoshi
N
Fujiyama
Yoshihide
Y
D002478:Cells, Cultured; D003106:Colon / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism*; D005347:Fibroblasts; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D053759:Interleukin-23; D053760:Interleukin-23 Subunit p19; D007378:Interleukins / Q000235:genetics*; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism; D021122:Protein Subunits / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D015854:Up-Regulation / Q000187:drug effects
C508840:IL23A protein, human; D007375:Interleukin-1; D053759:Interleukin-23; D053760:Interleukin-23 Subunit p19; D007378:Interleukins; D016328:NF-kappa B; D021122:Protein Subunits; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha