Decreased activity of neutrophils in the presence of diferuloylmethane (curcumin) involves protein kinase C inhibition.
Diferuloylmethane (curcumin) has been shown to act beneficially in arthritis, particularly through downregulated expression of proinflammatory cytokines and collagenase as well as through the modulated activities of T lymphocytes and macrophages. In this study its impact on activated neutrophils was investigated both in vitro and in experimental arthritis. Formation of reactive oxygen species in neutrophils was recorded on the basis of luminol- or isoluminol-enhanced chemiluminescence. Phosphorylation of neutrophil protein kinases C alpha and beta II was assessed by Western blotting, using phosphospecific antibodies. Adjuvant arthritis was induced in Lewis rats by heat-killed Mycobacterium butyricum. Diferuloylmethane or methotrexate was administered over a period of 28 days after arthritis induction. Under in vitro conditions, diferuloylmethane (1-100 microM) reduced dose-dependently oxidant formation both at extra- and intracellular level and it effectively reduced protein kinase C activation. Adjuvant arthritis was accompanied by an increased number of neutrophils in blood and by a more pronounced spontaneous as well as PMA (phorbol myristate acetate) stimulated chemiluminescence. Whereas the arthritis-related alterations in neutrophil count and in spontaneous chemiluminescence were not modified by diferuloylmethane, the increased reactivity of neutrophils to PMA was less evident in diferuloylmethane-treated animals. The effects of diferuloylmethane were comparable with those of methotrexate. Diferuloylmethane was found to be a potent inhibitor of neutrophil functions both in vitro and in experimental arthritis. As neutrophils are considered to be cells with the greatest capacity to inflict damage within diseased joints, the observed effects could represent a further mechanism involved in the antirheumatic activity of diferuloylmethane.
Jancinová
Viera
V
Institute of Experimental Pharmacology, Slovak Academy of Sciences, Dúbravská cesta 9, 84104 Bratislava, Slovakia. Viera.Jancinova@savba.sk
Perecko
Tomás
T
Nosál
Radomír
R
Kostálová
Daniela
D
Bauerová
Katarína
K
Drábiková
Katarína
K
D000255:Adenosine Triphosphate / Q000378:metabolism; D000328:Adult; D000818:Animals; D001169:Arthritis, Experimental / Q000097:blood / Q000188:drug therapy; D002273:Carcinogens / Q000494:pharmacology; D003474:Curcumin / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D007700:Kinetics; D049410:Luciferases, Renilla / Q000378:metabolism; D049449:Luminescence; D008163:Luminescent Measurements; D008297:Male; D008875:Middle Aged; D018375:Neutrophil Activation / Q000187:drug effects; D009504:Neutrophils / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism*; D010084:Oxidation-Reduction; D010766:Phosphorylation / Q000187:drug effects; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*; D051381:Rats; D011917:Rats, Inbred Lew; D016897:Respiratory Burst / Q000187:drug effects; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D055815:Young Adult
D002273:Carcinogens; D000255:Adenosine Triphosphate; D049410:Luciferases, Renilla; D011493:Protein Kinase C; D003474:Curcumin; D013755:Tetradecanoylphorbol Acetate