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


METHODS
MH7A cells and RA-FLS were stimulated either with interleukin (IL)-1β 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-κB) 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.


RESULTS
Curcumin effectively blocked IL-1β 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-1β. Furthermore, curcumin inhibited activation of NF-κB 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.


CONCLUSIONS
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.
Ludwig Boltzmann Cluster Rheumatology, Balneology and Rehabilitation, Ludwig Boltzmann Institute of Rheumatology and Balneology, Kurbadstrasse 14, 1100 Vienna, Austria. burkhard.kloesch@gmx.at
Burkhard
B
Kloesch
Tatjana
T
Becker
Elisabeth
E
Dietersdorfer
Hans
H
Kiener
Guenter
G
Steiner
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000009:adverse effects; D017209:Apoptosis / Q000187:drug effects; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000276:immunology; D002460:Cell Line; D003474:Curcumin / Q000008:administration & dosage* / Q000009:adverse effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005347:Fibroblasts / Q000187:drug effects* / Q000473:pathology; D006801:Humans; D053583:Interleukin-1beta / Q000276:immunology; D015850:Interleukin-6 / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D059808:Polyphenols / Q000008:administration & dosage* / Q000009:adverse effects; D013583:Synovial Membrane / Q000473:pathology; D013755:Tetradecanoylphorbol Acetate / Q000031:analogs & derivatives / Q000276:immunology; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D053583:Interleukin-1beta; D015850:Interleukin-6; D016328:NF-kappa B; D059808:Polyphenols; D042461:Vascular Endothelial Growth Factor A; C020922:4-O-methyl-12-O-tetradecanoylphorbol 13-acetate; D048049:Extracellular Signal-Regulated MAP Kinases; D003474:Curcumin; D013755:Tetradecanoylphorbol Acetate