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Epigallocatechin‐3‐gallate (EGCG) inhibits IL‐1β‐induced IL‐6 production and cyclooxygenase‐2 (COX‐2) expression in rheumatoid arthritis synovial fibroblasts in vitro
Author(s) -
Ahmed Salahuddin,
Pakozdi Angela,
Koch Alisa E.
Publication year - 2007
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.21.5.a47-d
Subject(s) - prostaglandin e2 , cyclooxygenase , chemistry , p38 mitogen activated protein kinases , stimulation , in vitro , fibroblast , kinase , prostaglandin e , arthritis , microbiology and biotechnology , protein kinase a , pharmacology , medicine , biology , biochemistry , enzyme
In the present study, we evaluated the efficacy of epigallocatechin‐3‐gallate (EGCG), a potent anti‐inflammatory molecule derived from green tea, in regulating interleukin‐1β (IL‐1β)‐induced IL‐6 and prostaglandin E 2 (PGE 2 ) production, and cyclooxygenase‐2 (COX‐2) expression in RA synovial fibroblasts. RA synovial fibroblasts were pretreated with EGCG (10–50 μ M) in serum‐free RPMI 1640, followed by IL‐1β (10 ng/ml) stimulation for 24 hours. IL‐1β stimulation resulted in a 160‐ and 115‐fold induction in IL‐6 and PGE 2 production, respectively (p<0.05, n ≥ 4 donors), and significantly enhanced the expression of COX‐2. Pretreatment with EGCG (10 μ M) blocked IL‐1β‐induced production of IL‐6 and PGE 2 by 16% and 49%, respectively (p<0.05, n ≥ 4 donors), whereas EGCG (50 μ M) almost completely abolished IL‐1β‐induced IL‐6 and PGE 2 production. In addition, EGCG inhibited IL‐1β‐induced RA synovial fibroblast COX‐2 expression in a concentration‐dependent fashion. Evaluation of the upstream signaling events revealed that EGCG specifically inhibited IL‐1β‐induced activation of protein kinase C (PKC)δ isoform and mitogen‐activated protein kinases (MAPKs), namely ERK1/2 and p38, and the nuclear translocation of nuclear factor‐κ Bp65 (NF‐κ Bp65). The results from this study suggest that EGCG may be of potential therapeutic value in regulating the joint destruction in RA.