Anti-inflammatory and apoptotic effects of the polyphenol curcumin on human fibroblast-like synoviocytes

作者：Kloesch Burkhard^*; Becker Tatjana; Dietersdorfer Elisabeth; Kiener Hans; Steiner Guenter

来源：International Immunopharmacology, 2013, 15(2): 400-405.

DOI：10.1016/j.intimp.2013.01.003

• Curcumin
• Synovial fibroblasts
• IL-6
• VEGF-A
• Apoptosis

Background: It has recently been reported that the polyphenol curcumin has pronounced anti-carcinogenic, anti-inflammatory and pro-apoptotic properties. This study investigated possible anti-inflammatory and apoptotic effects of curcumin on the human synovial fibroblast cell line MH7A, and on fibroblast-like synoviocytes (FLS) derived from patients with rheumatoid arthritis (RA). %26lt;br%26gt;Methods: MH7A cells and RA-FLS were stimulated either with interleukin (IL)-1 beta or phorbol 12-myristate 13 acetate (PMA), and treated simultaneously or sequentially with increasing concentrations of curcumin. Release of interleukin (IL)-6 and vascular endothelial growth factor (VEGF)-A was quantified by enzyme-linked immunosorbent assays (ELISAs). In MH7A cells, modulation of the transcription factor nuclear factor kappa-B (NF-kappa B) and mitogen-activated protein kinases (MAPKs) such as p38 and extracellular-signal regulated kinase (ERK1/2) were analysed by a reporter gene assay and Western blot, respectively. Pro-apoptotic events were monitored by Annexin-V/7-AAD based assay. Cleavage of pro-caspase-3 and -7 was checked with specific antibodies. %26lt;br%26gt;Results: Curcumin effectively blocked IL-1 beta and PMA-induced IL-6 expression both in MH7A cells and RA-FLS. VEGF-A expression could only be detected in RA-FLS and was induced by PMA, but not by IL-1 beta. Furthermore, curcumin inhibited activation of NF-kappa B and induced dephosphorylation of ERK1/2. Treatment of FLS with high concentrations of curcumin was associated with a decrease in cell viability and induction of apoptosis. %26lt;br%26gt;Conclusion: The natural compound curcumin represents strong anti-inflammatory properties and induces apoptosis in FLS. This study provides an insight into possible molecular mechanisms of this substance and suggests it as a natural remedy for the treatment of chronic inflammatory diseases like RA.

• 出版日期2013-2