TY - JOUR
T1 - Involvement of p38 mitogen-activated protein kinase in PLL-AGE-induced cyclooxgenase-2 expression
AU - Lin, Chien Huang
AU - Wu, Chih Hsiung
AU - Thum, Wai Yee
AU - Ho, Yuan Sun
AU - Lee, Horng Mo
N1 - Funding Information:
HML was supported by grant NSC-90-2320-B-038-030 from the National Science Council, Taipei, Taiwan, R.O.C. The authors wish to thank Shu-Ting Tsai and Shiau-Ren Leu for their skilled technical assistance.
PY - 2002/3/8
Y1 - 2002/3/8
N2 - In the present study, murine RAW 264.7 macrophages were incubated with poly-L-lysine-derived advanced glycosylation end products (PLL-AGEs) to examine cyclooxygenase-2 protein expression. Treatment of RAW 264.7 cells with PLL-AGEs caused the dose-dependent expression of cylooxygenase-2 but not cylooxygenase-1 and an increase in cylooxygenase activity. Increased cylooxygenase-2 expression was seen at 6 h and reached a maximum at 24 h. The tyrosine kinase inhibitor, genistein, and the p38 mitogen-activated protein kinase (MAPK) inhibitor, [4-(4-fluorophenyl)-2-(4-methylsulfinylphenyl)-5-(4-pyridyl)1H-imidazole] (SB 203580), inhibited PLL-AGE-induced cylooxygenase-2 expression, while the Ras inhibitor, FPT inhibitor II, and the MAP kinase kinase inhibitor, (2′-amino-3′-methoxyflavone) (PD 98059), had no effect on PLL-AGE-induced cylooxygenase-2 expression. Incubation of RAW 264.7 cells with PLL-AGEs resulted in activation of p38 MAPK, and this activation was suppressed by genistein and SB 203580. Taken together, our results suggest that activation of protein tyrosine kinase and p38 MAPK is involved in AGE-induced cyclooxygenase-2 expression in RAW 264.7 macrophages.
AB - In the present study, murine RAW 264.7 macrophages were incubated with poly-L-lysine-derived advanced glycosylation end products (PLL-AGEs) to examine cyclooxygenase-2 protein expression. Treatment of RAW 264.7 cells with PLL-AGEs caused the dose-dependent expression of cylooxygenase-2 but not cylooxygenase-1 and an increase in cylooxygenase activity. Increased cylooxygenase-2 expression was seen at 6 h and reached a maximum at 24 h. The tyrosine kinase inhibitor, genistein, and the p38 mitogen-activated protein kinase (MAPK) inhibitor, [4-(4-fluorophenyl)-2-(4-methylsulfinylphenyl)-5-(4-pyridyl)1H-imidazole] (SB 203580), inhibited PLL-AGE-induced cylooxygenase-2 expression, while the Ras inhibitor, FPT inhibitor II, and the MAP kinase kinase inhibitor, (2′-amino-3′-methoxyflavone) (PD 98059), had no effect on PLL-AGE-induced cylooxygenase-2 expression. Incubation of RAW 264.7 cells with PLL-AGEs resulted in activation of p38 MAPK, and this activation was suppressed by genistein and SB 203580. Taken together, our results suggest that activation of protein tyrosine kinase and p38 MAPK is involved in AGE-induced cyclooxygenase-2 expression in RAW 264.7 macrophages.
KW - Advanced
KW - Cyclooxygenase-2
KW - Glycosylation end product
KW - RAW 264.7 cell
KW - p38 MAP (mitogen activated protein) kinase
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U2 - 10.1016/S0014-2999(02)01285-2
DO - 10.1016/S0014-2999(02)01285-2
M3 - Article
C2 - 11909605
AN - SCOPUS:0037040405
SN - 0014-2999
VL - 438
SP - 143
EP - 152
JO - European Journal of Pharmacology
JF - European Journal of Pharmacology
IS - 3
ER -