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

Abstract

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.

Negative regulation of the inflammasome: keeping inflammation under control

“…Interestingly, it was shown that EGCG reduced NLRP3 and caspase-1 protein levels. In another study, EGCG diminished IL-1b production in response to calcium pyrophosphate dihydrate crystals in differentiated THP-1 macrophages and in fibroblast-like synoviocytes (154). In agreement with in vitro data, in vivo administration of EGCG in a lupus mouse model prevented kidney inflammation and pathology.…”

Anti‐inflammatory effects of polyphenols in arthritis

“…One of our previous studies demonstrated that EGCG is effective in reducing pro‐inflammatory cytokines and chemokines in FLS and monocytes stimulated with CPP crystals. The inhibition of the migration of neutrophils and mononuclear cells has also been observed in the presence of this polyphenol …”

“…Another important anti‐inflammatory effect exerted by EGCG has been demonstrated in OA fibroblast‐like synoviocytes (FLSs) and monocytes stimulated with calcium crystals which, in patients with OA, contribute to synovial inflammation and are associated with a more aggressive disease. In this model EGCG has been found to inhibit the release of cytokines such as IL‐1β, IL‐8, (C‐C motif) ligand 2 (CCL2) and transforming growth factor‐β (TGF‐β), while a role for EGCG in interfering with membrane organisation has also been highlighted …”

IL‐1ß and IL‐8 are scavenged by the hexadecylamide derivative of hyaluronic acid: A new mechanism

“…It has been possible to reproduce some inflammatory aspects associated to OA using CPP crystals in vitro . The recognition and phagocytosis of these crystals occurs in vivo through an involvement of specific TLRs and pattern recognition molecules .…”