Epigallocatechin-3-gallate reduces inflammation induced by calcium pyrophosphate crystals in vitro

Although osteoarthritis (OA) is defined as a cartilage disease, synovitis involving mononuclear cell infiltration and overexpression of proinflammatory mediators is common in early and late OA. Calcium crystals deposition is thought to be a factor that likely contributes to synovial inflammation. In recent years, significant interest has emerged in the beneficial health effects attributed to the green tea polyphenols and in particular to epigallocatechin-3-gallate (EGCG). It has been demonstrated that some of the actions of EGCG are linked to its ability to interfere with cell membranes. The objective of this study was to evaluate the influence of EGCG in some inflammatory aspects of OA and whether EGCG is able to interfere with membrane organization. We assessed the effect of EGCG on the production of proinflammatory cytokines and chemokines released by human fibroblast-like synoviocytes (FLS) and THP-1 cells stimulated with calcium pyrophosphate (CPP) crystals in presence of methyl-β-cyclodextrin (MβCD), a cholesterol-removing agent that disturbs lipid raft structures. The chemotactic effect of culture supernatants was also evaluated. EGCG inhibited interleukin (IL)-1β, transforming growth factor beta, IL-8, and chemokine (C-C motif) ligand 2 (CCL2) release by stimulated FLS and/or THP-1 cells in a dose-dependent manner. Supernatants of CPP-stimulated cells induced the migration of neutrophils and mononuclear cells which decreased in a dose-dependent manner in the presence of EGCG. EGCG increased cell viability when added to THP-1 cells treated with MβCD. Furthermore, MβCD enhanced the inflammatory response to CPP crystals increasing IL-8 and CCL2 secretion which was inhibited by EGCG in a dose-dependent manner. This study showed that EGCG is able to reduce the inflammatory response induced by CPP crystals in vitro. The identification of EGCG as dietary supplement capable of affording protection or modulating the inflammatory response to CPP crystals may have important implications in the prevention and treatment of OA and crystal-related arthropathies.