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

Abstract 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.