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Epigallocatechin‐3‐gallate (EGCG) inhibits IL‐1β‐induced chemokine production and MMP‐2 activation in rheumatoid arthritis synovial fibroblasts in vitro
Author(s) -
Ahmed Salahuddin,
Koch Alisa Erika
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a558-c
Subject(s) - chemokine , chemistry , interleukin 8 , stimulation , matrix metalloproteinase , microbiology and biotechnology , epigallocatechin gallate , pharmacology , immunology , inflammation , medicine , endocrinology , receptor , biology , biochemistry , antioxidant , polyphenol
In the present study, we evaluated the efficacy of epigallocatechin‐3‐gallate (EGCG), a potent anti‐inflammatory agent derived from green tea, in regulating interleukin‐1β (IL‐1β)‐induced production of the chemokines epithelial neutrophil activating peptide (ENA‐78), regulated upon activation normally T cell expressed and secreted (RANTES), and growth regulated oncogene‐α (Gro‐α), and matrix metalloproteinase (MMP)‐2 activity in RA synovial fibroblasts (RA‐SFs). To study the effect of EGCG on chemokine production, RA‐SFs were pretreated with EGCG (10–50μM) in serum‐free RPMI 1640, followed by IL‐1β (10 ng/ml) stimulation for 24 hours. IL‐1β stimulation resulted in a 5.2‐, 130‐, and 50‐fold induction in ENA‐78, RANTES, and Gro‐α production, respectively, in culture supernatants (p<.05, n=3 donors). Pretreatment with EGCG (10–50μM) blocked IL‐1β‐induced production of ENA‐78 by 64–88%, of RANTES by 80–96%, and of Gro‐α by 39–98% (p<.05, n=3 donors). Zymography results showed that EGCG blocked both the constitutive‐ and IL‐1β‐induced MMP‐2 activity in RA‐SFs. Evaluation of the upstream signaling events revealed that EGCG specifically blocked IL‐1β‐induced activation of protein kinase C (PKC)δ isoform and the nuclear translocation of nuclear factor‐κBp65 (NF‐κBp65). This study demonstrates the ability of EGCG in blocking IL‐1β‐induced chemokine production and MMP‐2 activation. EGCG may be of potential therapeutic value in RA. This study was supported by funds from NIH grants HL58695, AI40987, and AR48267, and funds from the Veterans Administration Research Service .