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Epigallocatechin‐3‐gallate (EGCG) inhibits IL‐6‐induced CRP synthesis and ameliorates adiponectin expression in Hep3B cells
Author(s) -
Madarampalli Bhanupriya,
Ahmed Salahuddin
Publication year - 2017
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.31.1_supplement.964.18
Subject(s) - stat3 , adiponectin , inflammation , phosphorylation , epigallocatechin gallate , signal transduction , stimulation , endocrinology , medicine , chemistry , biochemistry , insulin resistance , insulin , antioxidant , polyphenol
Elevated levels of C‐reactive protein (CRP) is associated with rheumatoid arthritis (RA) pathogenesis and plays a key role in inflammation, atherosclerosis, and vascular dysfunction during RA progression. Variety of pro‐inflammatory cytokines, including interleukin‐6 (IL‐6) regulate CRP synthesis in hepatocytes. In the current study, we tested the efficacy of epigallocatechin‐3‐gallate (EGCG), a potent anti‐inflammatory compound found in green tea, on IL‐6‐induced CRP expression in human hepatoma cell line (Hep3B). IL‐6 (25 ng/ml) stimulation induced CRP expression, both at the transcriptional and translational levels in Hep3B cells. Next, we pre‐incubated Hep3B cells with EGCG (5–20 mM) for 2h followed by IL‐6 stimulation (for 30 min and 24 h) to determine the effect on IL‐6‐induced signaling pathways, CRP and adiponectin expression, respectively. Adiponectin is an adipocyte specific protein with anti‐inflammatory property and negatively associated with CRP in RA patients. Pre‐incubation with EGCG significantly reduced IL‐6‐induced CRP to adiponectin expression ratio by ~1.6 to 21.4 fold (p<0.05) in a dose‐dependent manner. Evaluation of the underlying signaling pathways identified that EGCG potentially suppressed IL‐6‐induced phosphorylation of STAT3 at Ser 727 position. When compared to AG490 (an inhibitor of STAT3), we observed EGCG is more effective at reducing the phosphorylation of STAT3 at Ser 727 . Furthermore, blocking STAT3 phosphorylation in Hep3B, by either EGCG or AG490, significantly inhibited IL‐6‐induced CRP expression as determined by qRT‐PCR and ELISA. Altogether, our results suggest that EGCG blocks IL‐6‐induced CRP expression via STAT3 signaling pathway and stimulates adiponectin levels. Hence, EGCG could potentially suppress inflammation and atherosclerosis, which might aid in reducing cardiovascular co‐morbidity in RA. Support or Funding Information The study was supported by the NIH/NIAMS grant (AR‐063104).