期刊
EUROPEAN JOURNAL OF PHARMACOLOGY
卷 612, 期 1-3, 页码 161-166出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.ejphar.2009.03.080
关键词
Neutrophil; Extracellular and intracellular chemiluminescence; Protein kinase C phosphorylation; Diferuloymethane; Arthritis
资金
- Slovak Research and Development Agency [APVV-0315-07, APVV-51-017905]
- Scientific Grant Agency VEGA [2/7019/27]
Diferuloylmethane (curcumin) has been shown to act beneficially ill 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 oil activated neutrophils was investigated both ill vitro and in experimental arthritis. Formation of reactive oxygen species in neutrophils was recorded oil 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 mu M) 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 ill vitro and in experimental arthritis. As neutrophils ale 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. (C) 2009 Elsevier B.V. All rights reserved.
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