IL-17 Selectively Down-Regulates TNF-α-Induced RANTES Gene Expression in Human Colonic Subepithelial Myofibroblasts | Zendy

Akira Andoh | Zendy; Sanae Fujino | Zendy; Shigeki Bamba | Zendy; Yoshio Araki | Zendy; Takafumi Okuno | Zendy; Tadao Bamba | Zendy; Yoshihide Fujiyama | Zendy

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IL-17 Selectively Down-Regulates TNF-α-Induced RANTES Gene Expression in Human Colonic Subepithelial Myofibroblasts

Author(s) -

Akira Andoh,

Sanae Fujino,

Shigeki Bamba,

Yoshio Araki,

Takafumi Okuno,

Tadao Bamba,

Yoshihide Fujiyama

Publication year - 2002

Publication title -

the journal of immunology

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 2.737

H-Index - 372

eISSN - 1550-6606

pISSN - 0022-1767

DOI - 10.4049/jimmunol.169.4.1683

Subject(s) - tumor necrosis factor alpha , secretion , microbiology and biotechnology , gene expression , chemistry , alpha (finance) , gene , biology , endocrinology , medicine , biochemistry , construct validity , nursing , patient satisfaction

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.

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