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

Pharmacol Res. 2010 Feb;61(2):162-6. doi: 10.1016/j.phrs.2009.09.005. Epub 2009 Sep 25.

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-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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bridged-Ring Compounds / pharmacology
  • Carbazoles / pharmacology
  • Cell Line
  • Cyclooxygenase 2 / metabolism*
  • Dose-Response Relationship, Drug
  • Enzyme Activation
  • Estrenes / pharmacology
  • Indoles / pharmacology
  • Macrophages / drug effects*
  • Macrophages / enzymology
  • Mice
  • NF-kappa B / genetics
  • NF-kappa B / metabolism*
  • Norbornanes
  • Peptidoglycan / pharmacology*
  • Phosphodiesterase Inhibitors / pharmacology
  • Phosphoinositide Phospholipase C / antagonists & inhibitors
  • Phosphoinositide Phospholipase C / metabolism
  • Protein Kinase C / antagonists & inhibitors
  • Protein Kinase C / metabolism*
  • Protein Kinase Inhibitors / pharmacology
  • Pyrrolidinones / pharmacology
  • Signal Transduction / drug effects*
  • Thiocarbamates
  • Thiones / pharmacology
  • Time Factors
  • Transfection
  • Type C Phospholipases / antagonists & inhibitors
  • Type C Phospholipases / metabolism*

Substances

  • Bridged-Ring Compounds
  • Carbazoles
  • Estrenes
  • Indoles
  • NF-kappa B
  • Norbornanes
  • Peptidoglycan
  • Phosphodiesterase Inhibitors
  • Protein Kinase Inhibitors
  • Pyrrolidinones
  • Thiocarbamates
  • Thiones
  • 1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione
  • Go 6976
  • tricyclodecane-9-yl-xanthogenate
  • Ptgs2 protein, mouse
  • Cyclooxygenase 2
  • Protein Kinase C
  • Type C Phospholipases
  • Phosphoinositide Phospholipase C
  • phosphatidylcholine-specific phospholipase C
  • Ro 31-8220