Epigallocatechin-3-gallate ameliorates autoimmune arthritis by reciprocal regulation of T helper-17 regulatory T cells and inhibition of osteoclastogenesis by inhibiting STAT3 signaling

Abstract

The green tea polyphenol epigallocatechin-3-gallate is a potent antioxidant. Here, we describe the effects of epigallocatechin-3-gallate on T cell differentiation and osteoclast differentiation in an animal model of arthritis. Mice with collagen-induced arthritis were injected intraperitoneally with epigallocatechin-3-gallate, 3 times/wk after the primary immunization. Surface markers of T helper 17 cells and regulatory T cells were analyzed by flow cytometry. Flow cytometry, Western blotting, and enzyme-linked immunosorbent assays were used to evaluate the effect of epigallocatechin-3-gallate on cell signaling in the collagen-induced arthritis model. Epigallocatechin-3-gallate decreased the arthritis index and showed protective effects against joint destruction in collagen-induced arthritis mice. The expression of cytokines, oxidative stress proteins, and phosphorylated-signal transducer and activator of transcription-3, 705 and 727, were significantly less in mice treated with epigallocatechin-3-gallate than it was in controls. Epigallocatechin-3-gallate reduced the expression of osteoclast markers in vitro and in vivo relative to the control, and the antiosteoclastic activity was observed in epigallocatechin-3-gallate-treated, interferon-γ knockout mice. The proportion of forkhead box protein 3-positive regulatory T cells was increased in the spleens of mice treated with epigallocatechin-3-gallate compared with control mice, whereas the proportion of T helper 17 cells was reduced. In vitro, the expression of nuclear respiratory factor 2, heme oxygenase-1, and extracellular signal-regulated kinase was increased significantly by epigallocatechin-3-gallate. We demonstrated that the administration of epigallocatechin-3-gallate attenuated the symptoms of arthritis, inhibited osteoclastogenesis and T helper 17 cell activation, and increased the number of regulatory T cells. At the molecular level, the antiarthritic effects of epigallocatechin-3-gallate may be due to induction of phosphorylated-extracellular signal-regulated kinase, nuclear respiratory factor 2, and heme oxygenase-1 and inhibition of signal transducer and activator of transcription-3 activation.

Camellia Sinensis Modulates Telomerase in Collagen-Induced Arthritis

“…In our findings, a reduction in the clinical scores of joint inflammation and joint erosion were in agreement with the result of trial in which the green tea polyphenol epigallocatechin-3-gallateas a potent antioxidant improves autoimmune arthritis by both regulation of TH17 regulatory cells and inhibition of osteoclasts development [17]. Moreover, there is more evidence that polyphenols in green tea, particularly EGCG, inhibit matrix metalloproteinase activity which plays a fundamental role in pathogenesis of many diseases such as RA [18].…”

Red Wine Extract Disrupts Th17 Lymphocyte Differentiation in a Colorectal Cancer Context

“…[ 22 ] Thus, some reports have shown a potential effect of various polyphenols on Th17 in certain models of inflammation through a reduction of Th17 cell polarization leading a decrease of IL‐17 production. [ 31–36 ] In view of these studies showing the ability of certain polyphenols to act on different types of immune cells, it is possible that certain compounds may act synergistically to alter lymphocyte differentiation or to change the balance between Th17 lymphocytes and Treg cells. Moreover, the advantage of a complex mixture of polyphenols also lies in the fact that these different compounds have the ability to target multiple different and widely diverse targets.…”

Carbon Monoxide Releasing Molecule 3 Inhibits Osteoclastogenic Differentiation of RAW264.7 Cells by Heme Oxygenase-1

“…Overexpression of HO-1 modulates proinflammatory processes in a number of cells including macrophages and endothelial cells [39,40]. Moreover, the anti-inflammatory role of HO-1 has been addressed in models dealing with human diseases, such as lupus erythematosus and rheumatoid arthritis [41][42][43][44], which are typically associated with bone loss. HO-1 is therefore regarded as a potential target for the treatment of inflammatory diseases.…”