Journal
MOLECULAR MEDICINE REPORTS
Volume 14, Issue 4, Pages 3743-3748Publisher
SPANDIDOS PUBL LTD
DOI: 10.3892/mmr.2016.5719
Keywords
heparin: nuclear factor-kappa B; fibroblast-like synoviocyte
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Funding
- Science and Technology Project of Shenyang [F12-193-9-41]
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Fibroblast-like synoviocytes (FLSs) of rheumatoid arthritis (RA) lead to cartilage destruction, and the activation of NF-B is important in the proliferation of FLSs. Heparin is a glycosaminoglycan, which is widely used as an anticoagulant. In the present study, the effect of heparin on the tumor necrosis factor (TNF)- induced proliferation of FLSs was investigated. Western blot and polymerase chain reaction analyses were used to assess the expression levels of cytokines. The results revealed that TNF- induced the expression of interleukin (IL)-6, IL-8, TNF- and cyclin D1. Heparin inhibited the growth rate of the FLSs induced by TNF-. Heparin also decreased the TNF--induced mRNA and protein expression levels of IL-6, IL-8, TNF- and cyclin D1 in a dose-dependent manner. Immunofluorescence analysis showed that the expression of cytoplasmic TNF- was significantly reduced by heparin treatment. Furthermore, the levels of p65 and inhibitor of nuclear factor (NF)-B phosphorylation were inhibited by heparin treatment, suggesting that heparin induced the inhibition of NF-B. In conclusion, the results of the present study revealed that heparin inhibited the TNF--induced proliferation, cytokine production, expression of cyclin D1 and activation of NF-B signaling in FLSs, indicating the therapeutic potential of heparin in the treatment of RA.
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