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The Journal of Immunology, 2002, 169: 1683-1687.
Copyright © 2002 by The American Association of Immunologists

IL-17 Selectively Down-Regulates TNF-{alpha}-Induced RANTES Gene Expression in Human Colonic Subepithelial Myofibroblasts1

Akira Andoh2, Sanae Fujino, Shigeki Bamba, Yoshio Araki, Takafumi Okuno, Tadao Bamba and Yoshihide Fujiyama

Division of Gastroenterology, Shiga University of Medical Science, Otsu, Japan

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-{kappa}B DNA-binding activity, but markedly decreased TNF-{alpha}-induced IFN regulatory factor-1 (IRF-1) DNA-binding activity. Because cooperation between NF-{kappa}B 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.




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