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 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.
Andoh
Akira
A
Division of Gastroenterology, Shiga University of Medical Science, Otsu, Japan. andoh@belle.shiga-med.ac.jp
Fujino
Sanae
S
Bamba
Shigeki
S
Araki
Yoshio
Y
Okuno
Takafumi
T
Bamba
Tadao
T
Fujiyama
Yoshihide
Y
D001483:Base Sequence; D002478:Cells, Cultured; D018946:Chemokine CCL5 / Q000235:genetics* / Q000378:metabolism; D003106:Colon / Q000166:cytology / Q000187:drug effects* / Q000276:immunology* / Q000378:metabolism; D004247:DNA / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D005347:Fibroblasts / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D006801:Humans; D050856:Interferon Regulatory Factor-1; D020381:Interleukin-17 / Q000494:pharmacology*; D016328:NF-kappa B / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000187:drug effects; D020871:RNA Stability; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D018946:Chemokine CCL5; D004268:DNA-Binding Proteins; C494257:IRF1 protein, human; D050856:Interferon Regulatory Factor-1; D020381:Interleukin-17; D016328:NF-kappa B; D010750:Phosphoproteins; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D004247:DNA