Angiotensin II Induces C-Reactive Protein Expression via AT1-ROS-MAPK-NF-κB Signal Pathway in Hepatocytes

Background: C-reactive protein (CRP) participates in development of inflammatory diseases. Hepatocytes are a major contributor of circulating CRP. Although angiotensin II (Ang II) is known to evoke inflammatory response, it remains unknown whether Ang II induces CRP expression in hepatocytes. The pr...

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Main Authors: Jingjing Zhao, Juntian Liu, Xiaoming Pang, Shuyue Wang, Di Wu, Xiaolu Zhang, Liuxin Feng
Format: Article
Language:English
Published: Cell Physiol Biochem Press GmbH & Co KG 2013-09-01
Series:Cellular Physiology and Biochemistry
Subjects:
Online Access:http://www.karger.com/Article/FullText/354461
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author Jingjing Zhao
Juntian Liu
Xiaoming Pang
Shuyue Wang
Di Wu
Xiaolu Zhang
Liuxin Feng
author_facet Jingjing Zhao
Juntian Liu
Xiaoming Pang
Shuyue Wang
Di Wu
Xiaolu Zhang
Liuxin Feng
author_sort Jingjing Zhao
collection DOAJ
description Background: C-reactive protein (CRP) participates in development of inflammatory diseases. Hepatocytes are a major contributor of circulating CRP. Although angiotensin II (Ang II) is known to evoke inflammatory response, it remains unknown whether Ang II induces CRP expression in hepatocytes. The present study observed effect of Ang II on CRP expression and the related signal pathway in hepatocytes. Methods: mRNA and protein expressions in human hepatocytes were determined with RT-PCR and Western blot respectively. Reactive oxygen species (ROS) was measured using a fluorescence probe. CRP in liver and serum of rats was determined by immunohistochemistry and ELISA respectively. Results: Ang II induced mRNA and protein expression of CRP in hepatocytes and increased CRP production in liver and CRP level in serum. Losartan reduced Ang II- induced CRP expression in hepatocytes. Losartan and thenoyltrifluoroacetone decreased Ang II-stimulated ROS production. N-acetylcysteine antagonized Ang II-induced CRP expression. Losartan and N-acetylcysteine inhibited Ang II-activated ERK1/2. Unlike ERK1/2, only losartan inhibited Ang II-activated JNK. Furthermore, pyrrolidine dithiocarbamate abolished Ang II-induced CRP expression. Conclusion: Ang II has ability to induce CRP expression in hepatocytes in vitro and in vivo through AT1 receptor followed by ROS, MAPK and NF-κB signal pathway.
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spelling doaj.art-16df6b4a63704dcba0669c3c08b25a732022-12-21T20:19:17ZengCell Physiol Biochem Press GmbH & Co KGCellular Physiology and Biochemistry1015-89871421-97782013-09-0132356958010.1159/000354461354461Angiotensin II Induces C-Reactive Protein Expression via AT1-ROS-MAPK-NF-κB Signal Pathway in HepatocytesJingjing ZhaoJuntian LiuXiaoming PangShuyue WangDi WuXiaolu ZhangLiuxin FengBackground: C-reactive protein (CRP) participates in development of inflammatory diseases. Hepatocytes are a major contributor of circulating CRP. Although angiotensin II (Ang II) is known to evoke inflammatory response, it remains unknown whether Ang II induces CRP expression in hepatocytes. The present study observed effect of Ang II on CRP expression and the related signal pathway in hepatocytes. Methods: mRNA and protein expressions in human hepatocytes were determined with RT-PCR and Western blot respectively. Reactive oxygen species (ROS) was measured using a fluorescence probe. CRP in liver and serum of rats was determined by immunohistochemistry and ELISA respectively. Results: Ang II induced mRNA and protein expression of CRP in hepatocytes and increased CRP production in liver and CRP level in serum. Losartan reduced Ang II- induced CRP expression in hepatocytes. Losartan and thenoyltrifluoroacetone decreased Ang II-stimulated ROS production. N-acetylcysteine antagonized Ang II-induced CRP expression. Losartan and N-acetylcysteine inhibited Ang II-activated ERK1/2. Unlike ERK1/2, only losartan inhibited Ang II-activated JNK. Furthermore, pyrrolidine dithiocarbamate abolished Ang II-induced CRP expression. Conclusion: Ang II has ability to induce CRP expression in hepatocytes in vitro and in vivo through AT1 receptor followed by ROS, MAPK and NF-κB signal pathway.http://www.karger.com/Article/FullText/354461C-reactive proteinAngiotensin IIHepatocytesLiverInflammationAtherosclerosis
spellingShingle Jingjing Zhao
Juntian Liu
Xiaoming Pang
Shuyue Wang
Di Wu
Xiaolu Zhang
Liuxin Feng
Angiotensin II Induces C-Reactive Protein Expression via AT1-ROS-MAPK-NF-κB Signal Pathway in Hepatocytes
Cellular Physiology and Biochemistry
C-reactive protein
Angiotensin II
Hepatocytes
Liver
Inflammation
Atherosclerosis
title Angiotensin II Induces C-Reactive Protein Expression via AT1-ROS-MAPK-NF-κB Signal Pathway in Hepatocytes
title_full Angiotensin II Induces C-Reactive Protein Expression via AT1-ROS-MAPK-NF-κB Signal Pathway in Hepatocytes
title_fullStr Angiotensin II Induces C-Reactive Protein Expression via AT1-ROS-MAPK-NF-κB Signal Pathway in Hepatocytes
title_full_unstemmed Angiotensin II Induces C-Reactive Protein Expression via AT1-ROS-MAPK-NF-κB Signal Pathway in Hepatocytes
title_short Angiotensin II Induces C-Reactive Protein Expression via AT1-ROS-MAPK-NF-κB Signal Pathway in Hepatocytes
title_sort angiotensin ii induces c reactive protein expression via at1 ros mapk nf 954 b signal pathway in hepatocytes
topic C-reactive protein
Angiotensin II
Hepatocytes
Liver
Inflammation
Atherosclerosis
url http://www.karger.com/Article/FullText/354461
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