Green tea (Camellia sinensis) is one of the most commonly consumed beverages in the world, with no significant adverse side effects . Several epidemiological and experimental studies using animal models in the past two decades have verified the antioxidant, anti-inflammatory and anti-oncogenic properties of the various polyphenols named catechins found in green tea [14, 15]. Polyphenol-rich green tea extract (GTE) has shown inhibitory potential in selectively regulating cell growth, cell cycle and inducing apoptosis in cancer cells [16, 17]. Its anti-inflammatory properties were highlighted when the administration of GTE in drinking water to type II collagen immunized mice prevented the onset and severity of arthritis . We recently showed that epigallocatechin-3-gallate (EGCG), a major constituent of GTE, inhibits IL-1b-stimulation CC/CXC chemokine production and MMP-2 activation in RA synovial fibroblasts . We also showed recently that EGCG inhibits IL-6 synthesis and transsignalling in human RA synovial fibroblasts and rat adjuvant-induced arthritis (AIA) model . The aim of the present study was to decipher the mechanism of CC/CXC chemokine regulation and CC/CXC chemokine receptor expression caused by GTE treatment in human RA synovial fibroblasts and rat AIA model.
1. Composition of GTE
HPLC analysis showed that GTE contains 36% (w/w) of catechins, which included epigallocatechin (EGC, 11.5%), epicatechin (EC, 8%), epicatechin gallate (8%) and EGCG (5.9%).
2. Inhibition of IL-1b-induced RA synovial fibroblast chemokine production by GTE
RA synovial fibroblasts (2 104 /well) were incubated with GTE (0–40 mg/ml) for 12 h, followed by stimulation with IL-1b (10 ng/ml) for 24 h. The production of MCP-1/CCL2, RANTES/CCL5, GROa/CXCL2 and IL-8/CXCL8 in culture supernatants was measured using a commercially available ELISA kit. The values were mean and SEM. n: number of RA synovial fibroblast donors used. Fig.1
3. Transcriptional effect of GTE on IL-1b-induced chemokine production
The concentration of GTE used to inhibit chemokine production and chemokine receptor expression may be achieved by consuming GTE as a dietary supplement and may possibly have a preventative effect in regulating the course and clinical outcomes of RA in humans. On this line of investigation, it will be interesting to suggest future studies to evaluate the influence of dietary consumption of GTE on first-line conventional treatment options for RA such as MTX or other DMARDs for the possible better clinical outcome in animal models of arthritis. Further studies may be designed to improve the clinical outcome in animal models of RA through modification of the dose, and frequency of GTE administration may provide a better outcome and benefits of GTE in RA. In conclusion, the novel findings of this study are that GTE inhibits CC/CXC chemokine production, but up-regulates CC/CXCR chemokine receptor expression, in both RA synovial fibroblasts and rat AIA. Hence, it is suggested that the prophylactic use of GTE alone or as an adjunct treatment for human RA may be a beneficial therapeutic approach