Abstract
UTP causes IL-6 production in HaCaT keratinocytes, which is partially inhibited by PD98059, a mitogen-activated protein kinase kinase (MEK) inhibitor, suggesting that a pathway other than the extracellular signal-regulated kinase (ERK) pathway is involved in the production. In the present study, we examined the involvement of calcineurin in the UTP-induced interleukin (IL)-6 production in HaCaT keratinocytes. FK506 and cyclosporine A, calcineurin inhibitors, partially inhibited UTP-induced IL-6 mRNA expression and protein production. In addition, combined application of FK506 and PD98059 synergistically inhibited the UTP-induced IL-6 production. These results suggest that ERK and calcineurin are cooperatively involved in UTP-induced IL-6 production.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Calcineurin / pharmacology*
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Cell Line
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Cyclosporine / pharmacology
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Dose-Response Relationship, Drug
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Enzyme-Linked Immunosorbent Assay
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Extracellular Signal-Regulated MAP Kinases / antagonists & inhibitors
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Extracellular Signal-Regulated MAP Kinases / metabolism*
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Flavonoids / pharmacology
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Gene Expression / drug effects
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Humans
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Immunosuppressive Agents / pharmacology
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Interleukin-6 / biosynthesis*
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Interleukin-6 / genetics
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Keratinocytes / cytology
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Keratinocytes / drug effects*
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Keratinocytes / metabolism
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Protein Kinase Inhibitors / pharmacology
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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Reverse Transcriptase Polymerase Chain Reaction
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Tacrolimus / pharmacology
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Uridine Triphosphate / pharmacology*
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p38 Mitogen-Activated Protein Kinases / antagonists & inhibitors
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p38 Mitogen-Activated Protein Kinases / metabolism
Substances
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Flavonoids
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Immunosuppressive Agents
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Interleukin-6
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Protein Kinase Inhibitors
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RNA, Messenger
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Cyclosporine
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Extracellular Signal-Regulated MAP Kinases
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p38 Mitogen-Activated Protein Kinases
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Calcineurin
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2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one
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Uridine Triphosphate
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Tacrolimus