[Frontiers in Bioscience 18, 332-342, January 1, 2013]

Novel immunoregulatory properties of EGCG on reducing inflammation in EAE

Quanye Sun1,2, Yingxia Zheng1, Xia Zhang1,3, Xiaojuan Hu1, Yuanxia Wang1, Shimin Zhang4, Dongqing Zhang1, Hong Nie1

1Shanghai Institute of Immunology, Institutes of Medical Sciences, Shanghai JiaoTong University School of Medicine, 280 South Chongqing Road, Shanghai 200025, China; 2Department of Neurosurgery, the Fourth Affiliated Hospital of Harbin Medical University, 37 Yiyuan Street, Harbin 150001, China; 3Department of Clinical Laboratory, Shenzhen Children's Hospital, 7019 Yitian Road, Shenzhen 518026, China; 4Institute of Health Sciences, Shanghai Institutes of Biological Sciences, Chinese Academy of Sciences, 225 South Chongqing Road, Shanghai 200025, China

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. Materials and methods
3.1. Mice and reagents
3.2. Induction of EAE
3.3. EGCG treatment and evaluation of EAE
3.4. Histopathological analysis
3.5. LDH cytotoxicity assay
3.6. MOG-specific T cell response
3.7. Measurement of cytokine production
3.8. Isolation of mononuclear cells from mouse CNS tissue
3.9. Flow cytometric analysis
3.10. Immunoblot analysis
3.11. Quantitative real-time polymerase chain reaction (PCR)
3.12. Mouse Th1 and Th17 cell differentiation in vitro
3.13. Cell migration assay
3.14. Statistical analysis
4. Results
4.1. Amelioration of disease severity in EAE by EGCG
4.2. Regulatory effects of EGCG on encephalitogenic T cell responses
4.3. Selective down-regulation of STAT signaling pathway in encephalitogenic T cells by EGCG
4.4. Direct effect of EGCG on Th1 and Th17 cell differentiation
4.5. Reduced encephalitogenic lymphocyte migration by EGCG treatment
4.6. Altered expression of co-stimulatory molecules and reduced function of APCs by EGCG treatment
5. Discussion
6. Acknowledgments
7. References

1. ABSTRACT

EGCG is one of the major catechins in green tea. In this study, we investigated the novel regulatory mechanism of EGCG on amelioration of experimental autoimmune encephalomyelitis (EAE). The data showed that EGCG reduced disease severity in EAE by decreasing brain inflammation and demyelination damage, accompanied by decreased encephalitogenic T cell responses and reduced expression of inflammatory cytokines and chemokines. The effect of EGCG was attributable to its selective inhibition of interferon-gamma and interleukin-17 production in CD4+ T cells, mediated via alteration of the STAT pathway and the transcription factors T-bet and retinoid-related orphan receptor (ROR) gammat/ROR alpha. More important, EGCG has been found novel properties of directly inhibiting Th1 and Th17 cell differentiation in this study. On the other hand, EGCG-treated antigen presenting cells (APC) exhibited reduced co-stimulatory function as a result of altered expression of CD80 and CD86. The results of this study indicate that EGCG is a novel anti-inflammatory agent that could act as a useful drug for the treatment of multiple sclerosis and other neuroinflammatory diseases in the further.