Activation of the Neutrophil NADPH Oxidase Is Inhibited by SB 203580, a Specific Inhibitor of SAPK2/p38

• Published in: Biochemical and biophysical research communications Vol. 259; no. 2; pp. 465 - 470
• Main Authors: Lal, Aroon S., Clifton, Andrew D., Rouse, John, Segal, Anthony W., Cohen, Philip
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 07-06-1999
• Subjects: Calcium-Calmodulin-Dependent Protein Kinases - antagonists & inhibitors; Enzyme Activation - drug effects; Enzyme Inhibitors - pharmacology; Humans; Imidazoles - pharmacology; Mitogen-Activated Protein Kinases; N-Formylmethionine Leucyl-Phenylalanine - pharmacology; NADPH Oxidases - antagonists & inhibitors; Neutrophils - enzymology; p38 Mitogen-Activated Protein Kinases; Phosphorylation; Pyridines - pharmacology; Superoxides - metabolism; Tetradecanoylphorbol Acetate - pharmacology
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1006/bbrc.1999.0759

Activation of the neutrophil NADPH oxidase by either the bacterial peptide fMLP or phorbol myristate acetate (PMA) is partially suppressed by SB 203580, a specific inhibitor of the MAP kinase family member, SAPK2/p38. The concentration of SB 203580 that suppresses activation of NADPH oxidase is similar to that which inhibits SAPK2/p38 in vitro, and both fMLP and PMA induce an extremely rapid and potent activation of SAPK2/p38 in neutrophils. SB 203580 does not exert its effect by preventing the neutrophil priming reaction, by suppressing the phosphorylation of p47phax, or by preventing the translocation of p47phax/p67phax to the plasma membrane.