title: Epigallocatechin-3-gallate-mediated Tollip induction through the 67-kDa laminin receptor negatively regulating TLR4 signaling in endothelial cells.
abstract: BACKGROUND
  Green tea polyphenol epigallocatechin-3-gallate (EGCG) has the potential to impact a variety of inflammation-related diseases; however, the anti-inflammatory action of EGCG in endothelial cells has not been understood. Recently, we demonstrated that the 67-kDa laminin receptor (67LR) acts as a cell-surface EGCG receptor.
  
  
  OBJECTIVE
  This research was carried out to clarify the molecular basis for the down-regulation of toll-like receptor 4 (TLR4) signal transduction by EGCG in lipopolysaccharide (LPS)-stimulated endothelial cells.
  
  
  RESULTS
  RNAi-mediated silencing of 67LR resulted in an abrogation of the inhibitory action of EGCG on the LPS-induced activation of downstream signaling pathways. Also, we found that EGCG induced a rapid upregulation of Toll-interacting protein (Tollip), a negative regulator of TLR signaling, through 67LR in endothelial cells. RNAi-mediated silencing of Tollip impaired the TLR4 signaling inhibitory activity of EGCG. Additionally, silencing of Tollip resulted in an abrogation of the inhibitory action of EGCG on the LPS-induced expressions of cell-associated adhesion molecules, such as ICAM-1 and VCAM-1.
  
  
  CONCLUSIONS
  Taken together, these novel findings provide new insights into an understanding of negative regulatory mechanisms of the TLR4 signaling pathway and effective therapeutic intervention for the treatment of inflammatory disease.
authors.affiliation: Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup 580-185, Republic of Korea.
authors.forename: Eui-Baek
authors.initials: EB
authors.lastname: Byun
authors.affiliation: Department of Microbiology, Infection Signaling Network Research Center, College of Medicine, Chungnam National University, Daejeon, Republic of Korea.
authors.lastname: Mi-SoYang
authors.affiliation: Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup 580-185, Republic of Korea.
authors.forename: Jae-Hun
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup 580-185, Republic of Korea.
authors.forename: Du-Sup
authors.initials: DS
authors.lastname: Song
authors.affiliation: Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup 580-185, Republic of Korea.
authors.forename: Byung-Soo
authors.initials: BS
authors.lastname: Lee
authors.affiliation: Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup 580-185, Republic of Korea.
authors.forename: Jae-Nam
authors.initials: JN
authors.lastname: Park
authors.affiliation: Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup 580-185, Republic of Korea.
authors.forename: Sang-Hyun
authors.initials: SH
authors.lastname: Park
authors.affiliation: Department of Chemical Engineering, Kwangwoon University, 20 Kwangwoon-Ro, Nowon-Gu, Seoul, 139-701, Republic of Korea.
authors.forename: Chulhwan
authors.initials: C
authors.lastname: Park
authors.affiliation: Department of Food Science and Technology, Kongju National University, Yesan 340-800, Republic of Korea.
authors.forename: Pil-Mun
authors.initials: PM
authors.lastname: Jung
authors.affiliation: Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup 580-185, Republic of Korea. Electronic address: nig69@naver.com.
authors.forename: Nak-Yun
authors.initials: NY
authors.lastname: Sung
authors.affiliation: Department of Food Science and Technology, Kongju National University, Yesan 340-800, Republic of Korea. Electronic address: ehbyun80@kongju.ac.kr.
authors.forename: Eui-Hong
authors.initials: EH
authors.lastname: Byun
mesh_terms: D000818:Animals; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism; D042783:Endothelial Cells / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D017474:Receptors, Laminin / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism*
chemical_list: D015815:Cell Adhesion Molecules; D047908:Intracellular Signaling Peptides and Proteins; D008070:Lipopolysaccharides; D016328:NF-kappa B; D034741:RNA, Small Interfering; D017474:Receptors, Laminin; D051197:Toll-Like Receptor 4; C485837:Tollip protein, mouse; D002392:Catechin; C045651:epigallocatechin gallate; D020928:Mitogen-Activated Protein Kinases
keywords: 67-kDa laminin receptor; Cell-associated adhesion molecules; Endothelial cells; Epigallocatechin-3-gallate; Toll-interacting protein; Toll-like receptor