Involvement of nuclear factor-kappaB in lipoteichoic acid-induced cyclooxygenase-2 expression in RAW 264.7 macrophages.
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.
Chiang
L L
LL
School of Respiratory Therapy, Taipei Medical University, Taipei, Taiwan.
Kuo
C T
CT
Wang
C H
CH
Chen
T F
TF
Ho
Y S
YS
Kuo
H P
HP
Lin
C H
CH
D000818:Animals; D018929:Cell Culture Techniques; D051546:Cyclooxygenase 2; D007527:Isoenzymes / Q000096:biosynthesis*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008264:Macrophages / Q000502:physiology*; D051379:Mice; D016328:NF-kappa B / Q000494:pharmacology*; D010713:Phosphatidylcholines / Q000737:chemistry; D010716:Phosphatidylinositols / Q000737:chemistry; D010740:Phospholipases / Q000737:chemistry; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis*; D011493:Protein Kinase C / Q000494:pharmacology*; D013211:Staphylococcus aureus / Q000472:pathogenicity; D013682:Teichoic Acids / Q000494:pharmacology*
D007527:Isoenzymes; D008070:Lipopolysaccharides; D016328:NF-kappa B; D010713:Phosphatidylcholines; D010716:Phosphatidylinositols; D013682:Teichoic Acids; C009900:lipoteichoic acid; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D011493:Protein Kinase C; D010740:Phospholipases