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.
In this study, we examined the role of phosphatidylcholine-phospholipase C (PC-PLC) and protein kinase C (PKC) in peptidoglycan (PGN)-induced nuclear factor-kappaB (NF-kappaB) 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 kappaB-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-kappaB activation, and ultimately induces COX-2 expression in RAW 264.7 macrophages.
Department of Anesthesiology, Chi-Mei Medical Center, Tainan, Taiwan, ROC.
Jam-Inn
JI
Tzeng
Bing-Chang
BC
Chen
Huey-Mei
HM
Chang
Jhi-Joung
JJ
Wang
Munisamy
M
Sureshbabu
Ming-Hsien
MH
Chien
Ming-Jen
MJ
Hsu
Mauo-Ying
MY
Bien
Wen-Ta
WT
Chiu
Chuang-Ye
CY
Hong
Chien-Huang
CH
Lin
D000818:Animals; D001952:Bridged-Ring Compounds / Q000494:pharmacology; D002227:Carbazoles / Q000494:pharmacology; D002460:Cell Line; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D004963:Estrenes / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects* / Q000201:enzymology; D051379:Mice; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D009636:Norbornanes; D010457:Peptidoglycan / Q000494:pharmacology*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D054801:Phosphoinositide Phospholipase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011760:Pyrrolidinones / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects*; D013859:Thiocarbamates; D013871:Thiones / Q000494:pharmacology; D013997:Time Factors; D014162:Transfection; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors / Q000378:metabolism*
D001952:Bridged-Ring Compounds; D002227:Carbazoles; D004963:Estrenes; D007211:Indoles; D016328:NF-kappa B; D009636:Norbornanes; D010457:Peptidoglycan; D010726:Phosphodiesterase Inhibitors; D047428:Protein Kinase Inhibitors; D011760:Pyrrolidinones; D013859:Thiocarbamates; D013871:Thiones; C060229:1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione; C081021:Go 6976; C046498:tricyclodecane-9-yl-xanthogenate; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; D011493:Protein Kinase C; D010738:Type C Phospholipases; D054801:Phosphoinositide Phospholipase C; C105598:phosphatidylcholine-specific phospholipase C; C064758:Ro 31-8220