Involvement of p38 MAP kinase in not only activation of the phagocyte NADPH oxidase induced by formyl-methionyl-leucyl-phenylalanine but also determination of the extent of the activity.
Activated NADPH oxidase in neutrophils produces superoxide. We investigated the role of p38 MAP kinase in activating NADPH oxidase stimulated by the bacteria-derived peptide fMLP. fMLP-stimulated superoxide production was completely abolished by SB203580, a p38 MAP kinase inhibitor, whereas anisomycin, a p38 MAP kinase activator, did not induce superoxide production, indicating that p38 MAP kinase was essential, but not sufficient, for NADPH oxidase activation. Anisomycin pretreatment strongly activated p38 MAP kinase in fMLP-stimulated cells, accompanied by greatly increased superoxide production, suggesting that p38 MAP kinase determines the extent of the fMLP-stimulated NADPH oxidase activity. Furthermore, superoxide production was remarkably reactivated by cytochalasin B addition after fMLP-stimulated production had disappeared, and this was correlated with highly activated p38 MAP kinase. These results suggest that p38 MAP kinase is involved not only in activating NADPH oxidase stimulated by fMLP but also in determining the extent of its activity.
Sakamoto
Kei
K
Department of Molecular and Cellular Biochemistry, Graduate School of Medical Sciences, Kyushu University, 3-1-1, Maidashi, Higashi-ku, Fukuoka 812-8582.
Kuribayashi
Futoshi
F
Nakamura
Michio
M
Takeshige
Koichiro
K
D000841:Anisomycin / Q000494:pharmacology; D003571:Cytochalasin B / Q000494:pharmacology; D004789:Enzyme Activation; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology*; D019255:NADPH Oxidases / Q000378:metabolism*; D010586:Phagocytes / Q000187:drug effects / Q000201:enzymology*; D011725:Pyridines / Q000494:pharmacology; D013481:Superoxides / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*
D007093:Imidazoles; D011725:Pyridines; D013481:Superoxides; D003571:Cytochalasin B; D009240:N-Formylmethionine Leucyl-Phenylalanine; D000841:Anisomycin; D019255:NADPH Oxidases; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580