Paraoxonase-1 is related to inflammation, fibrosis and PPAR delta in experimental liver disease.
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.
Marsillach
Judit
J
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
Camps
Jordi
J
Ferré
Natàlia
N
Beltran
Raul
R
Rull
Anna
A
Mackness
Bharti
B
Mackness
Michael
M
Joven
Jorge
J
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
C491766:Ccl2 protein, rat; D018932:Chemokine CCL2; D005609:Free Radicals; D047494:PPAR delta; D002251:Carbon Tetrachloride; D043303:Aryldialkylphosphatase