1 This study investigated the role of protein kinase C (PKC) and transcription factor nuclear factor-kB (NF-kB) in cyclooxygenase-2 (COX-2) expression caused by lipoteichoic acid (LTA), a cell wall component of the gram-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 release in A549 cells. The LTA-induced increases in COX-2 expression and COX activity were markedly inhibited by dexamethasone, actinomycin D or cyclohexamide, but not by polymyxin B, which binds and inactivates endotoxin. 3 The phosphatidylcholine-phospholipase C (PC-PLC) inhibitor (D-609) and the phosphatidate phosphohydrolase inhibitor (propranolol) reduced the LTA-induced increases in COX-2 expression and COX activity, while phosphatidylinositol-phospholipase C inhibitor (U-73122) had no e ect. The PKC inhibitors (Go 6976, Ro 31-8220 and GF 109203X) and NF-kB 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 the plasma membrane; this stimulatory e ect was inhibited by D-609, propranolol, or Go 6976, but not by U-73122. 5 Exposure of A549 cells to LTA caused a translocation of p65 NF-kB from the cytosol to the nucleus and a degradation of IkB-a in the cytosol. Treatment of A549 cells with LTA caused NF-kB activation by detecting the formation of NF-kB-speci®c DNA-protein complex in the nucleus; this e ect 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 phosphatidylcholine-phospholipase D to induce PKC activation, which in turn initiates NF-kB activation, and ®nally induces COX-2 expression and PGE 2 release in human pulmonary epithelial cell line.
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