Involvement of phosphatidylcholine-phospholipase C and protein kinase C in peptidoglycan-induced nuclear factor-kappaB activation and cyclooxygenase-2 expression in RAW 264.7 macrophages.

Involvement of phosphatidylcholine-phospholipase C and protein kinase C in peptidoglycan-induced nuclear factor-kappaB activation and cyclooxygenase-2 expression in RAW 264.7 macrophages.
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DOI:
10.1016/j.phrs.2009.09.005
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发表时间:
2010-02
影响因子:
9.3
通讯作者:
Jam-Inn Tzeng;Bing-Chang Chen;Huey-Mei Chang;Jhi-Joung Wang;M. Sureshbabu;M. Chien;M. Hsu;M. Bien;W. Chiu;C. Hong;Chien-Huang Lin
Jam-Inn Tzeng;Bing-Chang Chen;Huey-Mei Chang;Jhi-Joung Wang;M. Sureshbabu;M. Chien;M. Hsu;M. Bien;W. Chiu;C. Hong;Chien-Huang Lin
中科院分区:
医学1区
文献类型:
--
作者:
Jam-Inn Tzeng;Bing-Chang Chen;Huey-Mei Chang;Jhi-Joung Wang;M. Sureshbabu;M. Chien;M. Hsu;M. Bien;W. Chiu;C. Hong;Chien-Huang Lin

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本研究探讨了磷脂酰胆碱-磷脂酶C(PC-PLC)和蛋白激酶C(PKC)在肽聚糖诱导的RAW 264.7巨噬细胞核因子-κB(NF-κB)活化和环氧合酶-2(COX-2)表达中的作用。PGN诱导的COX-2表达可被PC-PLC抑制剂(D609)和PKC抑制剂(GO6976和RO31-8220)减弱,但不能被磷脂酰肌醇-PLC(PI-PLC)抑制剂(U-73122)所抑制。Pgn可引起PKC活性增加,D609、GO6976和Ro31-8220可抑制这种作用,但U-73122不能抑制这种作用。此外,D609和Ro31-8220也能抑制PgN介导的κB-荧光素酶活性的升高。我们的研究结果表明,在RAW 264.7巨噬细胞中,PGN激活PC-PLC,进而诱导PKC活化,进而启动NF-κB的活化,最终诱导COX-2的表达。
In this study, we examined the role of phosphatidylcholine–phospholipase C (PC–PLC) and protein kinase C (PKC) in peptidoglycan (PGN)-induced nuclear factor-κB (NF-κB) activation and cyclooxygenase-2 (COX-2) expression in RAW 264.7 macrophages. PGN-induced COX-2 expression was attenuated by a PC–PLC inhibitor (D609) and by PKC inhibitors (Go 6976 and Ro 31-8220), but not by a phosphatidylinositol–PLC (PI–PLC) inhibitor (U-73122). PGN caused an increase in PKC activity, and this effect was inhibited by D609, Go 6976, and Ro 31-8220, but not by U-73122. Furthermore, the PGN-mediated increases in κB-luciferase activity were also inhibited by D609 and Ro 31-8220. Our data demonstrate that PGN activates PC–PLC which induces PKC activation; this in turn initiates NF-κB activation, and ultimately induces COX-2 expression in RAW 264.7 macrophages.