title: EGCG attenuates autoimmune arthritis by inhibition of STAT3 and HIF-1α with Th17/Treg control.
abstract: Epigallocatechin-3-gallate (EGCG) is a green tea polyphenol exerting potent anti-oxidant and anti-inflammatory effects by inhibiting signaling and gene expression. The objective of the study was to evaluate the effect of EGCG on interleukin (IL)-1 receptor antagonist knockout (IL-1RaKO) autoimmune arthritis models. IL-1RaKO arthritis models were injected intraperitoneally with EGCG three times per week after the first immunization. EGCG decreased the arthritis index and showed protective effects against joint destruction in the IL-1RaKO arthritis models. The expression of pro-inflammatory cytokines, oxidative stress proteins, and p-STAT3 (Y705) and p-STAT3 (S727), mTOR and HIF-1α were significantly lower in mice treated with EGCG. EGCG reduced osteoclast markers in vivo and in vitro along with anti-osteoclastic activity was observed in EGCG-treated IL-1RaKO mice. The proportion of Foxp3(+) Treg cells increased in the spleens of mice treated with EGCG, whereas the proportion of Th17 cells reduced. In vitro, p-STAT3 (Y705) and p-STAT3 (S727), HIF1α and glycolytic pathway molecules were decreased by EGCG. EGCG suppressed the activation of mTOR and subsequently HIF-1α, which is considered as a metabolic check point of Th17/Treg differentiation supporting the therapeutic potential of EGCG in autoimmune arthritis.
authors.affiliation: The Rheumatism Research Center, Catholic Research Institute of Medical Science, The Catholic University of Korea, Seoul, South Korea ; Laboratory of Immune Network, Conversant Research Consortium in Immunologic Disease, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, South Korea.
authors.forename: Eun-Ji
authors.initials: EJ
authors.lastname: Yang
authors.affiliation: Center for Rheumatic Disease, Division of Rheumatology, Department of Internal Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea, Banpo-dong, Seocho-gu, Seoul, South Korea.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Lee
authors.affiliation: The Rheumatism Research Center, Catholic Research Institute of Medical Science, The Catholic University of Korea, Seoul, South Korea ; Laboratory of Immune Network, Conversant Research Consortium in Immunologic Disease, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, South Korea.
authors.forename: Seon-Young
authors.initials: SY
authors.lastname: Lee
authors.affiliation: The Rheumatism Research Center, Catholic Research Institute of Medical Science, The Catholic University of Korea, Seoul, South Korea ; Laboratory of Immune Network, Conversant Research Consortium in Immunologic Disease, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, South Korea.
authors.forename: Eun-Kyung
authors.initials: EK
authors.lastname: Kim
authors.affiliation: The Rheumatism Research Center, Catholic Research Institute of Medical Science, The Catholic University of Korea, Seoul, South Korea ; Laboratory of Immune Network, Conversant Research Consortium in Immunologic Disease, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, South Korea.
authors.forename: Young-Mee
authors.initials: YM
authors.lastname: Moon
authors.affiliation: Division of Rheumatology, Department of Internal Medicine, Hallym University Kang-Nam Sacred Heart Hospital, Seoul, Korea.
authors.forename: Young Ok
authors.initials: YO
authors.lastname: Jung
authors.affiliation: Center for Rheumatic Disease, Division of Rheumatology, Department of Internal Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea, Banpo-dong, Seocho-gu, Seoul, South Korea.
authors.forename: Sung-Hwan
authors.initials: SH
authors.lastname: Park
authors.affiliation: The Rheumatism Research Center, Catholic Research Institute of Medical Science, The Catholic University of Korea, Seoul, South Korea ; Laboratory of Immune Network, Conversant Research Consortium in Immunologic Disease, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, South Korea.
authors.forename: Mi-La
authors.initials: ML
authors.lastname: Cho
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000737:chemistry*; D001168:Arthritis / Q000235:genetics / Q000378:metabolism; D001327:Autoimmune Diseases / Q000235:genetics; D002392:Catechin / Q000031:analogs & derivatives* / Q000737:chemistry; D002454:Cell Differentiation; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D007249:Inflammation; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D010010:Osteoclasts / Q000166:cytology; D018384:Oxidative Stress; D017472:Receptors, Interleukin-1 / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D058504:Th17 Cells / Q000276:immunology*
chemical_list: D000975:Antioxidants; C497443:Hif1a protein, mouse; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D017472:Receptors, Interleukin-1; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; D002392:Catechin; C045651:epigallocatechin gallate