Induction of cyclooxygenase-2 protein by lipoteichoic acid from Staphylococcus aureus in human pulmonary epithelial cells: involvement of a nuclear factor-kappa B-dependent pathway

1 This study investigated the role of protein kinase C (PKC) and transcript ion factor nuclear factor-kappaB (NF-kappaB) in cyclooxygenase-2 (COX-2) ex pression caused by lipoteichoic acid (LTA), a cell wall component of the gr am-positive bacterium Staphylococcus aureus, in human pulmonary epithelial cell line (A549). 2 LTA caused dose- and time-dependent increases in COX-2 expression and COX activity, and a dose-dependent increase in PGE(2) releas e in A549 cells. The LTA-induced increases in COX- 2 expression and COX activity were markedly inhibited by dexamethasone, act inomycin D or cyclohexamide, but not by polymyxin B, which binds and inacti vates endotoxin. 3 The phosphatidylcholine-phospholipase C (PC-PLC) inhibitor (D-609) and th e phosphatidate phosphohydrolase inhibitor (propranolol) reduced the LTA-in duced increases in COX-2 expression and COX activity, while phosphatidylino sitol-phospholipase C inhibitor (U-73122) had no effect. The PKC inhibitors (Go 6976, Ro 31-8220 and GF 109203X) and NF-kappaB inhibitor, pyrrolidine dithiocarbamate (PDTC), also attenuated the LTA-induced increases in COX-2 expression and COX activity. 4 Treatment of A549 cells with LTA caused an increase in PKC activity in th e plasma membrane; this stimulatory effect was inhibited by D-609, proprano lol, or Go 6976, but not by U-73122. 5 Exposure of A549 cells to LTA caused a translocation of p65 NF-kappaB fro m the cytosol to the nucleus and a degradation of I kappaB-alpha in the cyt osol. Treatment of A549 cells with LTA caused NF-kappaB activation by detec ting the formation of NF-kappaB-specific DNA-protein complex in the nucleus ; this effect was inhibited by dexamethasone, D-609, propranolol, Go 6976, Ro 31-8220, or PDTC. 6 These results suggest that LTA might activate PC-PLC and phosphatidylchol ine-phospholipase D to induce PKC activation, which in turn initiates NF-ka ppaB activation, and finally induces COX-2 expression and PGE(2) release in human pulmonary epithelial cell line.