Lipoteichoic acid-induced cyclooxygenase-2 expression requires activations of p44/42 and p38 mitogen-activated protein kinase signal pathways.
This study investigated the role of p44/42 and p38 mitogen-activated protein kinase (MAPK) in cyclooxygenase-2 expression caused by lipoteichoic acid in human pulmonary epithelial cell line (A549). Lipoteichoic acid-induced increases in cyclooxygenase activity and cyclooxygenase-2 expression were attenuated by tyrosine kinase inhibitors (genistein and tyrphostin AG126), a MAPK/extracellular signal-regulated protein kinase (MEK) inhibitor [2'-amino-3'-methoxyflavone] (PD 98059) and a p38 MAPK inhibitor [4-(4-fluorophenyl)-2-(4-methylsulfinylphenyl)-5-(4-pyridyl)1H-imidazole] (SB 203580). Lipoteichoic acid-induced p44/42 MAPK activation was inhibited by protein kinase C (PKC) inhibitors [12-(2-cyanoethyl)6,7,12,13-tetrahydro-13-methyl-5-oxo-5H-indolo(2,3-a)pyrrolo(3,4-c)-carbazole] (Go 6976) and [3-[1-[3-(amidinothio)propyl-1H-indol-3-yl]-3-(1-methyl-1H-indol-3-yl)maleimide]] (Ro 31-8220), genistein and PD 98059. Lipoteichoic acid-induced increase in p38 MAPK activity was inhibited by Go 6976, Ro 31-8220, genistein and SB 203580. Lipoteichoic acid-mediated formation of nuclear factor-kappa B (NF-kappa B)-specific DNA-protein complex was inhibited by genistein, tyrphostin AG126, PD 98059 and SB 203580. These results suggest that the activations of both p44/42 and p38 MAPK by lipoteichoic acid result in stimulation of NF-kappa B-specific DNA-protein binding and subsequent cyclooxygenase-2 expression in A549 cells. Both events required activation of upstream tyrosine kinase and PKC.
Lin
Chien-Huang
CH
Graduate Institute of Biomedical Technology, Taipei Medical University, Taipei, Taiwan, ROC. chlin@tmu.edu.tw
Kuan
I-Hui
IH
Wang
Chun-Hua
CH
Lee
Horng-Mo
HM
Lee
Wen-Sen
WS
Sheu
Joen-Rong
JR
Hsiao
George
G
Wu
Chih-Hsiung
CH
Kuo
Han-Pin
HP
D015153:Blotting, Western; D051546:Cyclooxygenase 2; D024202:Electrophoretic Mobility Shift Assay; D004847:Epithelial Cells; D006801:Humans; D007527:Isoenzymes / Q000096:biosynthesis*; D008070:Lipopolysaccharides / Q000378:metabolism / Q000494:pharmacology*; D008168:Lung / Q000166:cytology; D008565:Membrane Proteins; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism; D011112:Polymyxin B / Q000494:pharmacology; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D015398:Signal Transduction; D013682:Teichoic Acids / Q000378:metabolism / Q000494:pharmacology*; D013997:Time Factors; D014407:Tumor Cells, Cultured; D048051:p38 Mitogen-Activated Protein Kinases
D007527:Isoenzymes; D008070:Lipopolysaccharides; D008565:Membrane Proteins; D016328:NF-kappa B; D013682:Teichoic Acids; C009900:lipoteichoic acid; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D011505:Protein-Tyrosine Kinases; D011493:Protein Kinase C; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D011112:Polymyxin B