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Gallic acid, a natural polyphenolic acid, induces apoptosis and inhibits proin?ammatory gene expressions in rheumatoid arthritis ?broblast-like synoviocytes

Authors
 Chong-Hyeon Yoon  ;  Soo-Jin Chung  ;  Sang-Won Lee  ;  Yong-Beom Park  ;  Soo-Kon Lee  ;  Min-Chan Park 
Citation
 JOINT BONE SPINE, Vol.80(3) : 274-279, 2013 
Journal Title
JOINT BONE SPINE
ISSN
 1297-319X 
Issue Date
2013
MeSH
Apoptosis/drug effects* ; Arthritis, Rheumatoid/drug therapy* ; Arthritis, Rheumatoid/genetics ; Arthritis, Rheumatoid/immunology ; Cell Survival/drug effects ; Cells, Cultured ; Fibroblasts/cytology ; Fibroblasts/drug effects* ; Fibroblasts/physiology ; Gallic Acid/pharmacology* ; Gene Expression Regulation/drug effects* ; Gene Expression Regulation/immunology ; Humans ; In Situ Nick-End Labeling ; Polyphenols/pharmacology ; Real-Time Polymerase Chain Reaction ; Synovial Membrane/cytology ; Synovial Membrane/drug effects* ; Synovial Membrane/physiology
Keywords
Rheumatoid arthritis ; Fibroblast-like synoviocytes ; Gallic acid ; Apoptosis ; Inflammation
Abstract
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.
Full Text
http://www.sciencedirect.com/science/article/pii/S1297319X1200200X
DOI
10.1016/j.jbspin.2012.08.010
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Park, Min Chan(박민찬) ORCID logo https://orcid.org/0000-0003-1189-7637
Park, Yong Beom(박용범)
Lee, Sang-Won(이상원) ORCID logo https://orcid.org/0000-0002-8038-3341
Lee, Soo Kon(이수곤)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/86962
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