IL-17 selectively down-regulates TNF-alpha-induced RANTES gene expression in human colonic subepithelial myofibroblasts

IL-17 enhances the TNF-alpha-induced IL-6 and IL-8 secretion in human colonic subepithelial myofibroblasts. In this study, we investigated how IL-17 modulates RANTES secretion in these cells. TNF-alpha potently induced RANTES secretion, but IL-17 dose-dependently inhibited the TNF-alpha-induced RANT...

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Bibliographic Details
Published in:The Journal of immunology (1950) 2002-08, Vol.169 (4), p.1683-1687
Main Authors: Andoh, Akira, Fujino, Sanae, Bamba, Shigeki, Araki, Yoshio, Okuno, Takafumi, Bamba, Tadao, Fujiyama, Yoshihide
Format: Article
Language:English
Subjects:
Base Sequence
Cells, Cultured
Chemokine CCL5 - genetics
Chemokine CCL5 - metabolism
Colon - cytology
Colon - drug effects
Colon - immunology
Colon - metabolism
DNA - genetics
DNA - metabolism
DNA-Binding Proteins - metabolism
Down-Regulation - drug effects
Fibroblasts - drug effects
Fibroblasts - immunology
Fibroblasts - metabolism
Humans
Interferon Regulatory Factor-1
Interleukin-17 - pharmacology
NF-kappa B - metabolism
Phosphoproteins - metabolism
Promoter Regions, Genetic - drug effects
RNA Stability
RNA, Messenger - genetics
RNA, Messenger - metabolism
Transcription, Genetic - drug effects
Tumor Necrosis Factor-alpha - pharmacology
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Summary:IL-17 enhances the TNF-alpha-induced IL-6 and IL-8 secretion in human colonic subepithelial myofibroblasts. In this study, we investigated how IL-17 modulates RANTES secretion in these cells. TNF-alpha potently induced RANTES secretion, but IL-17 dose-dependently inhibited the TNF-alpha-induced RANTES secretion. This was also observed at the mRNA level. Even after pretreatment with TNF-alpha for 12 h, the inhibitory effect of IL-17 was detectable. IL-17 did not affect the TNF-alpha-induced stability of the RANTES gene. IL-17 significantly decreased the TNF-alpha-induced increase in RANTES promoter activity, and IL-17 actually blocked the TNF-alpha-induced RANTES gene transcription. EMSAs demonstrated that IL-17 did not modulate the TNF-alpha-induced NF-kappaB DNA-binding activity, but markedly decreased TNF-alpha-induced IFN regulatory factor-1 (IRF-1) DNA-binding activity. Because cooperation between NF-kappaB and IRF-1 is important in the TNF-alpha-induced RANTES gene expression, the major mechanism mediating the inhibitory effect of IL-17 may be achieved by the inhibition of IRF-1 DNA-binding activity.
ISSN:0022-1767
1550-6606
DOI:10.4049/jimmunol.169.4.1683