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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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Published in: | The Journal of immunology (1950) 2002-08, Vol.169 (4), p.1683-1687 |
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container_title | The Journal of immunology (1950) |
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creator | Andoh, Akira Fujino, Sanae Bamba, Shigeki Araki, Yoshio Okuno, Takafumi Bamba, Tadao Fujiyama, Yoshihide |
description | 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. |
doi_str_mv | 10.4049/jimmunol.169.4.1683 |
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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.</description><identifier>ISSN: 0022-1767</identifier><identifier>EISSN: 1550-6606</identifier><identifier>DOI: 10.4049/jimmunol.169.4.1683</identifier><identifier>PMID: 12165487</identifier><language>eng</language><publisher>United States</publisher><subject>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</subject><ispartof>The Journal of immunology (1950), 2002-08, Vol.169 (4), p.1683-1687</ispartof><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c377t-790845a19a0a11edba80b788d93479fcf2b0f84d705031999f0755b635497ffb3</citedby><cites>FETCH-LOGICAL-c377t-790845a19a0a11edba80b788d93479fcf2b0f84d705031999f0755b635497ffb3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12165487$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Andoh, Akira</creatorcontrib><creatorcontrib>Fujino, Sanae</creatorcontrib><creatorcontrib>Bamba, Shigeki</creatorcontrib><creatorcontrib>Araki, Yoshio</creatorcontrib><creatorcontrib>Okuno, Takafumi</creatorcontrib><creatorcontrib>Bamba, Tadao</creatorcontrib><creatorcontrib>Fujiyama, Yoshihide</creatorcontrib><title>IL-17 selectively down-regulates TNF-alpha-induced RANTES gene expression in human colonic subepithelial myofibroblasts</title><title>The Journal of immunology (1950)</title><addtitle>J Immunol</addtitle><description>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.</description><subject>Base Sequence</subject><subject>Cells, Cultured</subject><subject>Chemokine CCL5 - genetics</subject><subject>Chemokine CCL5 - metabolism</subject><subject>Colon - cytology</subject><subject>Colon - drug effects</subject><subject>Colon - immunology</subject><subject>Colon - metabolism</subject><subject>DNA - genetics</subject><subject>DNA - metabolism</subject><subject>DNA-Binding Proteins - metabolism</subject><subject>Down-Regulation - drug effects</subject><subject>Fibroblasts - drug effects</subject><subject>Fibroblasts - immunology</subject><subject>Fibroblasts - metabolism</subject><subject>Humans</subject><subject>Interferon Regulatory Factor-1</subject><subject>Interleukin-17 - pharmacology</subject><subject>NF-kappa B - metabolism</subject><subject>Phosphoproteins - metabolism</subject><subject>Promoter Regions, Genetic - drug effects</subject><subject>RNA Stability</subject><subject>RNA, Messenger - genetics</subject><subject>RNA, Messenger - metabolism</subject><subject>Transcription, Genetic - drug effects</subject><subject>Tumor Necrosis Factor-alpha - pharmacology</subject><issn>0022-1767</issn><issn>1550-6606</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2002</creationdate><recordtype>article</recordtype><recordid>eNqFkU1v1DAURS0EokPhFyAhr9hleE78ES-rqoVKoyLBsLbs5LnjyrFDnFDm35NRB7Fk8-7m3KsnHULeM9hy4PrTYxiGJeW4ZVJv-Xrb5gXZMCGgkhLkS7IBqOuKKakuyJtSHgFAQs1fkwtWMyl4qzbk6W63ErRgxG4OvzAeaZ-fUjXhwxLtjIXu728rG8eDrULqlw57-u3qfn_znT5gQoq_xwlLCTnRkOhhGWyiXY45hY6WxeEY5gPGYCMdjtkHN2UXbZnLW_LK21jw3TkvyY_bm_31l2r39fPd9dWu6hql5kppaLmwTFuwjGHvbAtOtW2vG66073ztwLe8VyCgYVprD0oIJxvBtfLeNZfk4_PuOOWfC5bZDKF0GKNNmJdi1KlUC_ZfkK1_SNmKFWyewW7KpUzozTiFwU5Hw8CcxJi_YswqxnBzErO2PpznFzdg_69zNtH8AVb4jLo</recordid><startdate>20020815</startdate><enddate>20020815</enddate><creator>Andoh, Akira</creator><creator>Fujino, Sanae</creator><creator>Bamba, Shigeki</creator><creator>Araki, Yoshio</creator><creator>Okuno, Takafumi</creator><creator>Bamba, Tadao</creator><creator>Fujiyama, Yoshihide</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7T5</scope><scope>H94</scope><scope>7X8</scope></search><sort><creationdate>20020815</creationdate><title>IL-17 selectively down-regulates TNF-alpha-induced RANTES gene expression in human colonic subepithelial myofibroblasts</title><author>Andoh, Akira ; 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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. 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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 |
title | IL-17 selectively down-regulates TNF-alpha-induced RANTES gene expression in human colonic subepithelial myofibroblasts |
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