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-Induced RANTES Gene Expression in Human Colonic Subepithelial Myofibroblasts1
Division of Gastroenterology, Shiga University of Medical Science, Otsu, Japan
IL-17 enhances the TNF-
-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- potently induced RANTES secretion, but IL-17 dose-dependently
inhibited the TNF--induced RANTES secretion. This was also observed
at the mRNA level. Even after pretreatment with TNF- for 12 h,
the inhibitory effect of IL-17 was detectable. IL-17 did not affect the
TNF--induced stability of the RANTES gene. IL-17 significantly
decreased the TNF--induced increase in RANTES promoter activity, and
IL-17 actually blocked the TNF--induced RANTES gene transcription.
EMSAs demonstrated that IL-17 did not modulate the TNF--induced
NF-
B DNA-binding activity, but markedly decreased TNF--induced
IFN regulatory factor-1 (IRF-1) DNA-binding activity. Because
cooperation between NF-B and IRF-1 is important in the
TNF--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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