Contribution of Extracellular Signal-Regulated Kinase to UTP-Induced Interleukin-6 Biosynthesis in HaCaT Keratinocytes
UTP causes interleukin (IL)-6 production via mRNA expression through P2Y2/P2Y4 receptors in human HaCaT keratinocytes. In the present study, we analyzed the mechanism of UTP-induced IL-6 production in these cells. UTP, an agonist of P2Y2/P2Y4 receptors, induced phosphorylation of extracellular signa...
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doaj-4356db6603714610842d25a7fc46f12f2020-11-24T23:53:19ZengElsevierJournal of Pharmacological Sciences1347-86132006-01-011024368376Contribution of Extracellular Signal-Regulated Kinase to UTP-Induced Interleukin-6 Biosynthesis in HaCaT KeratinocytesDaisaku Kobayashi0Satoko Ohkubo1Norimichi Nakahata2Department of Cellular Signaling, Graduate School of Pharmaceutical Sciences, Tohoku University, Aoba 6-3, Aramaki, Aoba-ku, Sendai 980-8578, JapanNational Institute of Sciences, Kamiyouga 1-18-1, Setagaya-ku, Tokyo 158-8501, JapanDepartment of Cellular Signaling, Graduate School of Pharmaceutical Sciences, Tohoku University, Aoba 6-3, Aramaki, Aoba-ku, Sendai 980-8578, Japan; Tohoku University 21st Century COE Program “CRESCENDO”, Sendai 980-8578, Japan; Corresponding author. nakahata@mail.pharm.tohoku.ac.jpUTP causes interleukin (IL)-6 production via mRNA expression through P2Y2/P2Y4 receptors in human HaCaT keratinocytes. In the present study, we analyzed the mechanism of UTP-induced IL-6 production in these cells. UTP, an agonist of P2Y2/P2Y4 receptors, induced phosphorylation of extracellular signal-regulated kinase (ERK) in a concentration- and time-dependent manner. PD98059, a MEK (mitogen-activated protein kinase kinase) inhibitor, and BAPTA-AM [O,O’-bis(2-aminophenyl)ethyleneglycol-N,N,N’,N’-tetraacetic acid, tetraacetoxymethyl ester], an intracellular Ca2+ chelator, reduced UTP-induced ERK phosphorylation and IL-6 mRNA expression. 2-APB [(2-aminoethoxy)diphenylborane], an inositol 1,4,5-trisphosphate (IP3)-receptor antagonist, inhibited UTP-induced IL-6 mRNA expression; and the action of A23187, a Ca2+ ionophore, resembled the action of UTP. In contrast, protein kinase C (PKC) downregulation and pertussis toxin did not affect UTP-induced IL-6 mRNA expression, suggesting that PKC and Gi are not involved in the UTP-induced IL-6 production. However, AG1478, an epidermal growth factor (EGF)-receptor inhibitor, partially decreased UTP-induced ERK phosphorylation and IL-6 expression. These results suggest that UTP-induced IL-6 production is in part mediated via phosphorylation of ERK through Gq/11/IP3/[Ca2+]i and transactivation of the EGF receptor. Keywords:: interleukin-6, extracellular signal-regulated kinase (ERK), HaCaT, Ca2+ elevation, epidermal growth factor (EGF) receptorhttp://www.sciencedirect.com/science/article/pii/S134786131934349X |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Daisaku Kobayashi Satoko Ohkubo Norimichi Nakahata |
spellingShingle |
Daisaku Kobayashi Satoko Ohkubo Norimichi Nakahata Contribution of Extracellular Signal-Regulated Kinase to UTP-Induced Interleukin-6 Biosynthesis in HaCaT Keratinocytes Journal of Pharmacological Sciences |
author_facet |
Daisaku Kobayashi Satoko Ohkubo Norimichi Nakahata |
author_sort |
Daisaku Kobayashi |
title |
Contribution of Extracellular Signal-Regulated Kinase to UTP-Induced Interleukin-6 Biosynthesis in HaCaT Keratinocytes |
title_short |
Contribution of Extracellular Signal-Regulated Kinase to UTP-Induced Interleukin-6 Biosynthesis in HaCaT Keratinocytes |
title_full |
Contribution of Extracellular Signal-Regulated Kinase to UTP-Induced Interleukin-6 Biosynthesis in HaCaT Keratinocytes |
title_fullStr |
Contribution of Extracellular Signal-Regulated Kinase to UTP-Induced Interleukin-6 Biosynthesis in HaCaT Keratinocytes |
title_full_unstemmed |
Contribution of Extracellular Signal-Regulated Kinase to UTP-Induced Interleukin-6 Biosynthesis in HaCaT Keratinocytes |
title_sort |
contribution of extracellular signal-regulated kinase to utp-induced interleukin-6 biosynthesis in hacat keratinocytes |
publisher |
Elsevier |
series |
Journal of Pharmacological Sciences |
issn |
1347-8613 |
publishDate |
2006-01-01 |
description |
UTP causes interleukin (IL)-6 production via mRNA expression through P2Y2/P2Y4 receptors in human HaCaT keratinocytes. In the present study, we analyzed the mechanism of UTP-induced IL-6 production in these cells. UTP, an agonist of P2Y2/P2Y4 receptors, induced phosphorylation of extracellular signal-regulated kinase (ERK) in a concentration- and time-dependent manner. PD98059, a MEK (mitogen-activated protein kinase kinase) inhibitor, and BAPTA-AM [O,O’-bis(2-aminophenyl)ethyleneglycol-N,N,N’,N’-tetraacetic acid, tetraacetoxymethyl ester], an intracellular Ca2+ chelator, reduced UTP-induced ERK phosphorylation and IL-6 mRNA expression. 2-APB [(2-aminoethoxy)diphenylborane], an inositol 1,4,5-trisphosphate (IP3)-receptor antagonist, inhibited UTP-induced IL-6 mRNA expression; and the action of A23187, a Ca2+ ionophore, resembled the action of UTP. In contrast, protein kinase C (PKC) downregulation and pertussis toxin did not affect UTP-induced IL-6 mRNA expression, suggesting that PKC and Gi are not involved in the UTP-induced IL-6 production. However, AG1478, an epidermal growth factor (EGF)-receptor inhibitor, partially decreased UTP-induced ERK phosphorylation and IL-6 expression. These results suggest that UTP-induced IL-6 production is in part mediated via phosphorylation of ERK through Gq/11/IP3/[Ca2+]i and transactivation of the EGF receptor. Keywords:: interleukin-6, extracellular signal-regulated kinase (ERK), HaCaT, Ca2+ elevation, epidermal growth factor (EGF) receptor |
url |
http://www.sciencedirect.com/science/article/pii/S134786131934349X |
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