Objectives: To investigate whether gallic acid (3, 4, 5-trihydroxybenzoic acid), a natural polyphenolic acid found in gall nuts, sumac, oak bark, tea leaves, grapes and wine, has pro-apoptotic and anti-inflammatory effects on fibroblast-like synoviocytes (FLS) from patients with rheumatoid arthritis (RA). Methods: Viability of RA FLS was assessed using a MTT assay after gallic acid treatment. Apoptosis was assessed by TUNEL assay and caspase-3 activity was determined by a colorimetric assay. The levels of apoptosis-related proteins including Bcl-2, p-Akt, p53, and Bax were determined using western blot analyses, and the mRNA expressions of various pro-inflammatory mediators were measured using quantitative real-time PCR. Results: Cell viability of RA FLS was significantly decreased by treatment with 10 or more μM of gallic acid. Gallic acid treatment at the concentrations that do not affect cell viability (0.1 and 1. μM) induced cellular apoptosis of RA FLS. Treatment with 0.1 and 1. μM of gallic acid also resulted in a significant increase in caspase-3 activity and regulated the productions of Bcl-2, Bax, p53 and pAkt. The mRNA expression levels of pro-inflammatory cytokines (IL-1β, IL-6), chemokines (CCL-2/MCP-1, CCL-7/MCP-3), cyclooxygenase-2, and matrix metalloproteinase-9 from RA FLS were suppressed by the gallic acid treatment in dose-dependent manners. Conclusion: Gallic acid treatment was found to induce apoptosis of RA FLS through regulation of apoptosis-related protein expressions and to reduce the expression of pro-inflammatory genes in RA FLS. These data suggest that pro-apoptotic and anti-inflammatory activities of gallic acid may be used as a possible therapeutic option for RA.
Bibliographical noteFunding Information:
This study was supported by a grant from the Korean Health Technology R&D Project, Ministry for Health, Welfare & Family Affairs, Republic of Korea (A100134) and a grant from the Bumsuk Academic Scholarship Foundation, Republic of Korea (2009-0566). The authors are grateful to Tae-Yeon Kim and Eunji Lee (Gangnam Severance Hospital Biomedical Research Center) for technical assistance.
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