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Regulation of Prostaglandin E 2 (PGE 2 )‐induced IL‐6 production by Epigallocatechin‐3‐gallate (EGCG) in rheumatoid arthritis synovial fibroblasts
Author(s) -
AHMED SALAHUDDIN,
KWAN KEVIN,
MAROTTE HUBERT,
KOCH ALISA E.
Publication year - 2008
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.22.1_supplement.298.2
Subject(s) - prostaglandin e , chemistry , cytokine , prostaglandin e2 , medicine , endocrinology , prostaglandin e2 receptor , agonist , pharmacology , receptor , biochemistry
Prostaglandin E 2 (PGE 2 ) induces joint inflammation and bone destruction in rheumatoid arthritis (RA), at least in part, by producing the bone destructive cytokine interleukin‐6 (IL‐6) via E‐prostanoid (EP) receptors. In the present study using RA synovial fibroblasts, we evaluated ( a ) the mechanism through which PGE 2 induces IL‐6 production; and ( b ) the efficacy of green tea polyphenol epigallocatechin‐3‐gallate (EGCG) in suppressing PGE 2 ‐induced IL‐6 production. The results showed that PGE 2 induced time‐ and concentration‐dependent IL‐6 production in RA synovial fibroblasts, which was mimicked by a selective EP2 agonist, butaprost (p<0.05, n=4). Blockade of the EP4 receptor by a selective competitive antagonist GW627368X further enhanced PGE 2 induced IL‐6 production, suggesting a possible compensatory mechanism. Pretreatment with EGCG (10 and 20 μM) significantly inhibited PGE 2 ‐induced IL‐6 production in RA synovial fibroblasts (p<0.05, n=3). Evaluation of signaling pathways using specific inhibitors pointed to an important mediatory role of Janus protein tyrosine kinases (JAKs) and nuclear factor‐κB (NF‐κB) in PGE 2 ‐ induced IL‐6 production. These in vitro findings suggest that EGCG inhibits PGE 2 ‐induced IL‐6 production possibly via modulation of PGE 2 ‐induced JAK/STAT and NF‐κB pathways. Thus, EGCG may be of potential therapeutic value in regulating bone destruction observed in RA.