Synergistic effect of interferon-gamma and phorbol myristate acetate on superoxide production by human monocytes.
This study demonstrates a synergistic effect of IFN gamma and PMA on superoxide generation by human monocytes. A strict correlation was observed between the induction of superoxide production and PK-C activation by PMA alone. No such correlation was evident for IFN gamma. However, exposure of the cells to IFN gamma for 10 to 15 hr prior to PMA treatment enhanced both superoxide production and PK-C activation. Using protein kinase inhibitors, we noticed that while PMA exerted its effect by activating PK-C, IFN gamma operated via activation of calcium/calmodulin-dependent or some other calcium-dependent protein kinases. These kinases appeared to be involved in the effect of IFN gamma on superoxide production, as well as in its potentiation of PMA activity.
Department of Microbiology and Immunology, Faculty of Health Sciences, Ben Gurion University of the Negev, Israel.
M
M
Wolfson
I
I
Nathan
M
M
Aharon
A
A
Dvilansky
M
M
Aboud
D002478:Cells, Cultured; D003600:Cytosol / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D007700:Kinetics; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism*; D011493:Protein Kinase C / Q000097:blood; D011994:Recombinant Proteins; D013481:Superoxides / Q000097:blood*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
D011994:Recombinant Proteins; D013481:Superoxides; D007371:Interferon-gamma; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate