Study of regulatory mechanism of inflammatory response by purinergic signaling
| Project/Area Number |
16590201
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
General pharmacology
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| Research Institution | Fukushima Medical University School of Medicine |
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Principal Investigator |
MATSUOKA Isao Fukushima Med.Univ., Pharmacol., Assistant Professor, 医学部, 助教授 (10145633)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2005: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2004: ¥2,400,000 (Direct Cost: ¥2,400,000)
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| Keywords | P2 receptor / ATP / NTPDase1 / endothelial cells / macrophage / interferon-γ / inflammation / cyclooxygenase 2 / インターフェロンーγ / プロスタグランジンE2 / エクトヌクレオチダーゼ / TNF-α / P2X_4受容体 / CD39 / 繊維芽細胞 / Autotaxin |
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| Research Abstract |
We investigated whether the purinergic signaling system could be altered with inflammatory condition. Treatment of human umbilical vein endothelial cells(HUVEC) with IFN-γ enhanced ATP-induced increase in intracellular Ca^<2+> concentration. This effect of IFN-γ was resulted from up-regulation of P2X_4 receptor expression and down-regulation of nucleoside triphosphate diphosphohydrolase 1 (NTPDase1). Effects of IFN-γ on the purinergic signaling system in HUVEC were mediated by Jak-STAT pathway and further enhanced synergistically by other inflammatory cytokines, such as IL-1β and TNF-α. Stimulation of quiescent HUVEC by ATP caused a rapid induction of cyclooxyganase(COX) 2 mRNA, protein and enzyme activity. The effect of ATP was mediated by ionotropic receptors, probably P2X_4 receptors through a mechanism involving p38MAP kinase-mediated COX2 mRNA stabilization. The ATP-induced COX2 induction was augmented in IFN-γ-treated HUVEC. Unlike the effects on HUVEC, IFN-γ increased ATP hydrolysis in murine macrophage J774 cells in a time- and concentration-dependent manner, accompanied by marked increase in NTPDase1 mRNA. Up-regulation of NTPDase1 by IFN-γ was inhibited by cycloheximide, Jak inhibitor and orthovanadate, a protein tyrosine phosphatase inhibitor, but enhanced by tyrosine kinase inhibitors (herbimycin A, PP2 and genistein) and p42/44 MAP kinase inhibitors. These results suggest that IFN-γ causes the up-regulation of NTPDase1 in a tyrosine phosphatase-dependent manner. The differential regulation of NTPDase1 expression in macrophages and EC by IFN-γ may contribute to the macrophage-endothelium interaction under the vascular inflammation.
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Report
(3 results)
Research Products
(19 results)
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[Journal Article] Thrombin-induced rapid geranylgeranylation of RhoA as an essential process for RhoA activation in endothelial cells.2005
Author(s)
Ohkawa H, Ishibashi T, Sakamoto T, Sugimoto K, Nagata K, Yokoyama K, Sakamoto N, Kamioka M, Matsuoka I, Fukuhara S, Sugimoto N, Takuwa Y, Maruyama Y
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Journal Title
J Biol Chem 280
Pages: 10182-10188
Description
「研究成果報告書概要(和文)」より
Related Report
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[Journal Article] Thrombin-induced rapid geranylgeranylation of RhoA as an essential process for RhoA activation in endothelial cells.2005
Author(s)
Ohkawara H, Ishibashi T, Sakamoto T, Sugimoto K, Nagata K, Yokoyama K, Sakamoto N, Kamioka M, Matsuoka I, Fukuhara S, Sugimoto N, Takuwa Y, Maruyama Y
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Journal Title
J Biol Chem. 280
Pages: 10182-10188
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Journal Article] Thrombin-induced rapid geranylgeranylation of RhoA as an essential process for RhoA activation in endothelial cells.2005
Author(s)
Ohkawara H, Ishibashi T, Sakamoto T, Sugimoto K, Nagata K, Yokoyama K, Sakamoto N, Kamioka M, Matsuoka I, Fukuhara S, Sugimoto N, Takuwa Y, Maruyama Y
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Journal Title
J Biol Chem 280・11
Pages: 10182-10188
Related Report
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[Journal Article] Thrombin-induced rapid geranylgeranylation of RhoA as an essential process for RhoA activation in endothelial cells.
Author(s)
Ohkawara H, Ishibashi T, Sakamoto T, Sugimoto K, Nagata K, Yokoyama K, Sakamoto N, Kamioka M, Matsuoka I, Fukuhara S, Sugimoto N, Takuwa Y, Maruyama Y
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Journal Title
Related Report
