期刊
BIOCHEMICAL PHARMACOLOGY
卷 65, 期 3, 页码 377-388出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/S0006-2952(02)01485-5
关键词
cartilage; chondrocytes; cytokines; osteoarthritis; rhein
This study was designed to investigate the effects of them, the active metabolite of diacerhein, on the metabolic functions of human chondrocytes cultured in alginate beads. Enzymatically isolated ostcoarthritic (OA) chondrocytes were cultured in alginate beads in a well-defined culture medium for 12 days. Rhein was tested in a range of concentrations comprised between 10(-7) and 4 x 10(-5) M, in the presence or absence of 10(-10) M IL-1beta. Interleukin (IL)-6 and -8, macrophage inflammatory protein (MIP-1beta), stromelysin-1 (MMP-3), aggrecan (AGG), tissue inhibitor of metalloproteinases-1 (TIMP-1), prostaglandin E-2 (PGE(2)) and nitric oxide (NO) productions were assayed. Cyclooxygenase-2 (COX-2) and inducible NO synthase (iNOS) mRNA steady-state levels were also quantified. In the basal condition, 10(-5) M them increased by 46.5% the production of AGG, decreased by 17-30% the production of IL-6, MMP-3, NO and MIP-1beta but enhanced by 50% the production of PGE2(.) IL-1beta increased IL-6, IL-8, MIP-1beta, NO, PGE(2) and MMP-3 productions, but inhibited AGG and TIMP-1 synthesis. Rhein partially reversed the effect of IL-1beta on TIMP-1 and NO production, had no effect on AGG, IL-6 and MIP-1P production, but upregulated the IL-1beta stimulated PGE(2) production. The COX-2 and iNOS mRNA levels and IL-8 production were not modified by rhein. Overall, these results contribute to explain the clinical efficiency of rhein and give new information on its mechanisms of action. (C) 2002 Elsevier Science Inc. All rights reserved.
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