Phorbol 12-myristate 13-acetate (PMA)-induced oxyradical production in rheumatoid synovial cells.
We successfully detected the oxyradical production in human synovial A (macrophage-like) and B (fibroblast-like) cells by phorbol 12-myristate 13-acetate (PMA) using the luminol-chemiluminescence method. The PMA (0.1 microgram/ml)-induced photon generation was abolished by an O2- scavenger, superoxide dismutase, and an H2O2 scavenger, catalase, suggesting that the stimulus produced oxyradicals in synovial cells. Both of these responses were abolished by a protein kinase C (PKC) inhibitor, calphostine C, but unaffected by an intracellular Ca2+ chelator, BAPTA-AM, and Ca2+ removal from the extracellular medium. These findings suggest that synovial A and B cells produce oxyradicals through PKC-mediated and [Ca2+]i-independent mechanisms, probably through the activation of NADPH oxidase.
Tanabe
T
T
Department of Pharmacology, Kansai Medical University, Osaka, Japan.
Otani
H
H
Mishima
K
K
Ogawa
R
R
Inagaki
C
C
D001172:Arthritis, Rheumatoid / Q000378:metabolism / Q000473:pathology; D002118:Calcium / Q000378:metabolism; D002273:Carcinogens / Q000633:toxicity*; D002374:Catalase / Q000737:chemistry / Q000378:metabolism; D002614:Chelating Agents / Q000494:pharmacology; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism*; D007719:Knee Joint / Q000378:metabolism; D008163:Luminescent Measurements; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D009281:Naphthalenes / Q000494:pharmacology; D017785:Photons; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D013482:Superoxide Dismutase / Q000737:chemistry / Q000378:metabolism; D013481:Superoxides / Q000737:chemistry / Q000378:metabolism*; D013582:Synovial Fluid / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000633:toxicity*
D002273:Carcinogens; D002614:Chelating Agents; D004791:Enzyme Inhibitors; D009281:Naphthalenes; D013481:Superoxides; C070379:1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid acetoxymethyl ester; D004533:Egtazic Acid; D006861:Hydrogen Peroxide; D002374:Catalase; D013482:Superoxide Dismutase; D011493:Protein Kinase C; C058819:calphostin C; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium