期刊
INFLAMMATION RESEARCH
卷 55, 期 10, 页码 446-455出版社
SPRINGER BASEL AG
DOI: 10.1007/s00011-006-5067-5
关键词
thurine chloramine; p53 tumor suppressor; inflammation; rheumatoid arthritis; synoviocytes
Objective and Design: Taurine chloramine (Tau-C1), originating from activated neutrophils, possesses antiinflammatory activities. Fibroblast-like synoviocytes (FLS) participate in the chronic synovitis and synovial membrane hyperplasia that are characteristic pathological features of rheumatoid arthritis (RA). The present study was conducted to investigate the mechanism of the Tau-Cl effect on the proliferation of these cells in culture. Materials and methods: FLS were stimulated in vitro with platelet derived growth factor (PDGF) alone or together with Tau-Cl. Cell proliferation was evaluated by counting the total and dividing cell numbers and by measurement of H-3-thymidine incorporation. Expression of the key cell-cycle regulators was evaluated at the protein (Western blotting) and/or mRNA (RT-PCR) levels. Results: Treatment of RA FLS with Tau-Cl (200-500 mu M) resulted in an early nuclear accumulation of p53 tumor suppressor protein. Moreover, Tau-Cl inhibited PDGF-triggered cell proliferation (IC50 value approximate to 250-300 mu M), accompanied by characteristic modulation of p53 transcriptional targets: down-regulation of proliferating cell nuclear antigen (PCNA) and survivin, and concomitant up-regulation of p21 mitotic inhibitor. Conclusion: We propose that Tau-Cl inhibits proliferation of RA FLS by triggering a p53-dependent cell-cycle arrest and conclude that this compound suppresses pathways in FLS that are known to contribute to the pathology of RA.
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