Involvement of nuclear factor-kappaB in lipoteichoic acid-induced cyclooxygenase-2 expression in RAW 264.7 macrophages

J Pharm Pharmacol. 2003 Jan;55(1):115-23. doi: 10.1111/j.2042-7158.2003.tb02441.x.

Abstract

We have investigated the role of protein kinase C (PKC) and nuclear factor-kappaB (NF-kappaB) in cyclooxygenase-2 (COX-2) expression caused by Staphylococcus aureus lipoteichoic acid in RAW 264.7 macrophages. A phosphatidylcholine-phospholipase C (PC-PLC) inhibitor (D-609) and a phosphatidylinositol-phospholipase C (PI-PLC) inhibitor (U-73122) attenuated lipoteichoic acid-induced COX-2 expression, while a phosphatidate phosphohydrolase inhibitor (propranolol) had no effect. Two PKC inhibitors (Go 6976 and Ro 31-8220) and the NF-kappaB inhibitor, pyrrolidine dithiocarbamate (PDTC), also attenuated lipoteichoic acid-induced COX-2 expression. Lipoteichoic acid resulted in a decrease in PKC activity in the cytosol and an increase in PKC activity in membranes. The lipoteichoic acid-induced translocation of p65 NF-kappaB from the cytosol to the nucleus was inhibited by D-609, U-73122, Go 6976, Ro 31-8220, and PDTC, but not by propranolol. The results suggested that lipoteichoic acid might have activated PC-PLC and PI-PLC to induce PKC activation, which in turn initiated NF-kappaB activation, and finally induced COX-2 expression in RAW 264.7 macrophages.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Culture Techniques
  • Cyclooxygenase 2
  • Isoenzymes / biosynthesis*
  • Lipopolysaccharides / pharmacology*
  • Macrophages / physiology*
  • Mice
  • NF-kappa B / pharmacology*
  • Phosphatidylcholines / chemistry
  • Phosphatidylinositols / chemistry
  • Phospholipases / chemistry
  • Prostaglandin-Endoperoxide Synthases / biosynthesis*
  • Protein Kinase C / pharmacology*
  • Staphylococcus aureus / pathogenicity
  • Teichoic Acids / pharmacology*

Substances

  • Isoenzymes
  • Lipopolysaccharides
  • NF-kappa B
  • Phosphatidylcholines
  • Phosphatidylinositols
  • Teichoic Acids
  • lipoteichoic acid
  • Cyclooxygenase 2
  • Prostaglandin-Endoperoxide Synthases
  • Protein Kinase C
  • Phospholipases