title: Epigallocatechin-3-gallate inhibits angiotensin II-induced C-reactive protein generation through interfering with the AT1-ROS-ERK1/2 signaling pathway in hepatocytes.
abstract: Inflammation plays a key role in many chronic diseases such as cardiovascular diseases and liver diseases. As a representative inflammatory molecule, C-reactive protein (CRP) is mainly produced in the liver. Hepatic CRP plays a direct role in the inflammatory hepatic diseases and in development of atherosclerosis when entering into the blood circulation. In the present study, we observed the effect of epigallocatechin-3-gallate (EGCG) on Ang II-induced CRP generation in hepatocytes and the molecular mechanism. Rats were delivered with the subcutaneous infusion of Ang II and/or intragastric administration of EGCG for 7 days. Hepatocytes were pretreated with EGCG before stimulation with Ang II in vitro. CRP level in the serum and liver was determined with ELISA and the immunohistochemical staining. RNA and protein expressions were determined using RT-PCR and Western blot. The in vivo experiment confirmed that EGCG reduced not only CRP generation in the liver of Ang II-infused rats but also serum CRP level. The in vitro results showed that pretreatment of hepatocytes with EGCG inhibited Ang II-induced mRNA and protein expression of CRP in a concentration-dependent manner. Further study exhibited that EGCG downregulated AT1expression, attenuated Ang II-activated phosphorylation of ERK1/2, and upregulated Ang II-inhibited peroxisome proliferator-activated receptor gamma (PPARγ) expression in vitro and in vivo. In addition, EGCG decreased Ang II-stimulated reactive oxygen species (ROS) generation in hepatocytes. These demonstrate that EGCG is able to inhibit Ang II-induced CRP generation by interfering with AT1-ROS-ERK1/2 signal pathway in hepatocytes, which provides the new evidence and mechanism for the anti-inflammatory effect of EGCG.
authors: Department of Pharmacology, Xi'an Jiaotong University School of Medicine, 76 West Yanta Road, Xi'an, 710061, China.|Translational Medicine Center, Hong Hui Hospital, Xi' an Jiaotong University School of Medicine, Xi' an, 710054, China.
authors: Jingjing
authors: J
authors: Zhao
authors: Department of Pharmacology, Xi'an Jiaotong University School of Medicine, 76 West Yanta Road, Xi'an, 710061, China. ljt@xjtu.edu.cn.
authors: Juntian
authors: J
authors: Liu
authors: Department of Pharmacology, Xi'an Jiaotong University School of Medicine, 76 West Yanta Road, Xi'an, 710061, China.
authors: Xiaoming
authors: X
authors: Pang
authors: Department of Pharmacology, Xi'an Jiaotong University School of Medicine, 76 West Yanta Road, Xi'an, 710061, China.
authors: Xiaolu
authors: X
authors: Zhang
authors: Department of Pharmacology, Xi'an Jiaotong University School of Medicine, 76 West Yanta Road, Xi'an, 710061, China.
authors: Shuyue
authors: S
authors: Wang
authors: Department of Pharmacology, Xi'an Jiaotong University School of Medicine, 76 West Yanta Road, Xi'an, 710061, China.
authors: Di
authors: D
authors: Wu
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation; D022781:Hepatocytes / Q000187:drug effects* / Q000201:enzymology; D006801:Humans; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism*; D044140:Receptor, Angiotensin, Type 1 / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D013482:Superoxide Dismutase / Q000378:metabolism; D013997:Time Factors
chemical_list: C544065:AGTR1 protein, human; D000893:Anti-Inflammatory Agents; D002352:Carrier Proteins; C030929:Crp protein, rat; D047495:PPAR gamma; C000613696:PPAR gamma, rat; D017382:Reactive Oxygen Species; D044140:Receptor, Angiotensin, Type 1; D000804:Angiotensin II; D002392:Catechin; C045651:epigallocatechin gallate; D013482:Superoxide Dismutase; C535150:MAPK1 protein, human; C535149:Mapk1 protein, rat; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3
keywords: Angiotensin II; C-reactive protein; EGCG; Hepatocytes; Inflammation