Interleukin-17 augments tumor necrosis factor-α-induced granulocyte and granulocyte/macrophage colony-stimulating factor release from human colonic myofibroblasts
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- Andoh, A., Yasui, H., Inatomi, O. et al. J Gastroenterol (2005) 40: 802. doi:10.1007/s00535-005-1632-x
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Interleukin (IL)-17 is a newly identified T-cell-specific cytokine. In this study, we investigated the effects of IL-17 on colony-stimulating factor (CSF) release in human colonic subepithelial myofibroblasts (SEMFs).
CSF release and mRNA expression were determined by enzyme-linked immunosorbent assay (ELISA) and Northern blotting, respectively. Nuclear factor (NF)-κB- and activating protein (AP-1)-DNA binding activities were evaluated by electrophoretic gel mobility shift assays (EMSAs).
Unstimulated cells secreted a small amount of granulocyte G- and granulocyte/macrophage (GM)-CSF, and a considerable amount of M-CSF. IL-17 weakly enhanced G-CSF release, but did not affect GM- and M-CSF release. IL-17 selectively enhanced tumor necrosis factor (TNF)-α-induced G- and GM-CSF release. The combination of IL-17 plus TNF-α induced a marked increase in NF-κB- and AP-1-DNA binding activities. The adenovirus-mediated transfer of a stable form of IκBα and/or a dominant negative mutant of c-Jun markedly inhibited the IL-17 plus TNF-α-induced G- and GM-CSF mRNA expression. Furthermore, a stability study showed that IL-17 plus TNF-α markedly enhanced the stability of G- and GM-CSF mRNA.
IL-17 augments TNF-α-induced G- and GM-CSF release via transcriptional and posttranscriptional mechanisms.