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 AT1 expression, 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.
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All the experimental procedures carried out in this study are performed in accordance with the Guidelines for the Care and Use of Laboratory Animals of Xi’an Jiaotong University and approved by the Institutional Animal Care Committee of Xi’an Jiaotong University.
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Zhao, J., Liu, J., Pang, X. et al. Epigallocatechin-3-gallate inhibits angiotensin II-induced C-reactive protein generation through interfering with the AT1-ROS-ERK1/2 signaling pathway in hepatocytes. Naunyn-Schmiedeberg's Arch Pharmacol 389, 1225–1234 (2016). https://doi.org/10.1007/s00210-016-1279-6
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DOI: https://doi.org/10.1007/s00210-016-1279-6