title: Paraoxonase-1 is related to inflammation, fibrosis and PPAR delta in experimental liver disease.
abstract: BACKGROUND
  Paraoxonase-1 (PON1) is an antioxidant enzyme synthesized by the liver. It protects against liver impairment and attenuates the production of the pro-inflammatory monocyte chemoattractant protein-1 (MCP-1). We investigated the relationships between hepatic PON1 and MCP-1 expression in rats with liver disease and explored the possible molecular mechanisms involved.
  
  
  METHODS
  CCl4 was administered for up to 12 weeks to induce liver damage. Serum and hepatic levels of PON1 and MCP-1, their gene and protein expression, nuclear transcription factors, and histological and biochemical markers of liver impairment were measured.
  
  
  RESULTS
  High levels of PON1 and MCP-1 expression were observed at 12th week in the hepatocytes surrounding the fibrous septa and inflammatory areas. CCl4-administered rats had an increased hepatic PON1 concentration that was related to decreased gene transcription and inhibited protein degradation. Decreased PON1 gene transcription was associated with PPARdelta expression. These changes were accompanied by increased hepatic MCP-1 concentration and gene expression. There were significant direct relationships between hepatic PON1 and MCP-1 concentrations (P = 0.005) and between PON1 and the amount of activated stellate cells (P = 0.001).
  
  
  CONCLUSIONS
  Our results from this experimental model suggest a hepato-protective role for PON1 against inflammation, fibrosis and liver disease mediated by MCP-1.
authors.affiliation: Centre de Recerca Biomèdica, Hospital Universitari de Sant Joan, Institut d'Investigacions Sanitàries Pere Virgili, Universitat Rovira i Virgili, C, Sant Joan s/n, 43201 Reus, Spain. jmarsillach@grupsagessa.cat
authors.forename: Judit
authors.initials: J
authors.lastname: Marsillach
authors.forename: Jordi
authors.initials: J
authors.lastname: Camps
authors.forename: Natàlia
authors.initials: N
authors.lastname: Ferré
authors.forename: Raul
authors.initials: R
authors.lastname: Beltran
authors.forename: Anna
authors.initials: A
authors.lastname: Rull
authors.forename: Bharti
authors.initials: B
authors.lastname: Mackness
authors.forename: Michael
authors.initials: M
authors.lastname: Mackness
authors.forename: Jorge
authors.initials: J
authors.lastname: Joven
mesh_terms: D000818:Animals; D043303:Aryldialkylphosphatase / Q000502:physiology*; D002251:Carbon Tetrachloride; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology / Q000378:metabolism* / Q000473:pathology*; D018932:Chemokine CCL2 / Q000502:physiology; D005609:Free Radicals / Q000378:metabolism; D008106:Liver Cirrhosis, Experimental / Q000209:etiology / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D047494:PPAR delta / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
chemical_list: C491766:Ccl2 protein, rat; D018932:Chemokine CCL2; D005609:Free Radicals; D047494:PPAR delta; D002251:Carbon Tetrachloride; D043303:Aryldialkylphosphatase