Cooperation of calcineurin and ERK for UTP-induced IL-6 production in HaCaT keratinocytes.
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.
Kobayashi
Daisaku
D
Department of Cellular Signaling, Graduate School of Pharmaceutical Sciences, Tohoku University, Aoba 6-3, Aramaki, Aoba-ku, Sendai 980-8578, Japan. nakahata@mail.pharm.tohoku.ac.jp
Ohkubo
Satoko
S
Nakahata
Norimichi
N
D019703:Calcineurin / Q000494:pharmacology*; D002460:Cell Line; D016572:Cyclosporine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D005419:Flavonoids / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology; D015850:Interleukin-6 / Q000096:biosynthesis* / Q000235:genetics; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016559:Tacrolimus / Q000494:pharmacology; D014544:Uridine Triphosphate / Q000494:pharmacology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
D005419:Flavonoids; D007166:Immunosuppressive Agents; D015850:Interleukin-6; D047428:Protein Kinase Inhibitors; D012333:RNA, Messenger; D016572:Cyclosporine; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D019703:Calcineurin; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one; D014544:Uridine Triphosphate; D016559:Tacrolimus