title: Angiotensin II induces C-reactive protein expression via AT1-ROS-MAPK-NF-κB signal pathway in hepatocytes.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Pharmacology, Xi'an Jiaotong University School of Medicine, Xi'an, China.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Zhao
authors.forename: Juntian
authors.initials: J
authors.lastname: Liu
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Pang
authors.forename: Shuyue
authors.initials: S
authors.lastname: Wang
authors.forename: Di
authors.initials: D
authors.lastname: Wu
authors.forename: Xiaolu
authors.initials: X
authors.lastname: Zhang
authors.forename: Liuxin
authors.initials: L
authors.lastname: Feng
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D000804:Angiotensin II / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D002097:C-Reactive Protein / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D022781:Hepatocytes / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D019808:Losartan / Q000494:pharmacology; D008297:Male; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000037:antagonists & inhibitors / Q000378:metabolism; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects*; D013804:Thenoyltrifluoroacetone / Q000494:pharmacology
chemical_list: D016328:NF-kappa B; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D044140:Receptor, Angiotensin, Type 1; D011994:Recombinant Proteins; D000804:Angiotensin II; D013804:Thenoyltrifluoroacetone; D002097:C-Reactive Protein; D048031:JNK Mitogen-Activated Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D019808:Losartan; D000111:Acetylcysteine