title: Immune-regulation of the apolipoprotein A-I/C-III/A-IV gene cluster in experimental inflammation.
abstract: Apolipoprotein A-IV is a member of the apo A-I/C-III/A-IV gene cluster. In order to investigate its hypothetical coordinated regulation, an acute phase was induced in pigs by turpentine oil injection. The hepatic expression of the gene cluster as well as the plasma levels of apolipoproteins were monitored at different time periods. Furthermore, the involvement of the inflammatory mediators' interleukins 1 and 6 and tumor necrosis factor in the regulation of this gene cluster was tested in cultured pig hepatocytes, incubated with those mediators and apo A-I/C-III/A-IV gene cluster expression at the mRNA level was measured. In response to turpentine oil-induced inflammation, a decreased hepatic apo A-IV mRNA expression was observed (independent of apo A-I and apo C-III mRNA) not correlating with the plasma protein levels. The distribution of plasma apo A-IV experienced a shift from HDL to larger particles. In contrast, the changes in apo A-I and apo C-III mRNA were reflected in their corresponding plasma levels. Addition of cytokines to cultured pig hepatocytes also decreased apo A-IV and apo A-I mRNA levels. All these results show that the down-regulation of apolipoprotein A-I and A-IV messages in the liver may be mediated by interleukin 6 and TNF-alpha. The well-known HDL decrease found in many different acute-phase responses also appears in the pig due to the decreased expression of apolipoprotein A-I and the enlargement of the apolipoprotein A-IV-containing HDL.
authors.affiliation: Departamento de Bioquímica y Biología Molecular y Celular, Universidad de Zaragoza, Facultad de Veterinaria, Universidad de Zaragoza, Miguel Servet 177, E-50013 Zaragoza, Spain.
authors.forename: María A
authors.initials: MA
authors.lastname: Navarro
authors.forename: Rakel
authors.initials: R
authors.lastname: Carpintero
authors.forename: Sergio
authors.initials: S
authors.lastname: Acín
authors.forename: Jose Miguel
authors.initials: JM
authors.lastname: Arbonés-Mainar
authors.forename: Lucía
authors.initials: L
authors.lastname: Calleja
authors.forename: Ricardo
authors.initials: R
authors.lastname: Carnicer
authors.forename: Joaquín C
authors.initials: JC
authors.lastname: Surra
authors.forename: Mario A
authors.initials: MA
authors.lastname: Guzmán-García
authors.forename: Nieves
authors.initials: N
authors.lastname: González-Ramón
authors.forename: María
authors.initials: M
authors.lastname: Iturralde
authors.forename: Fermín
authors.initials: F
authors.lastname: Lampreave
authors.forename: Andrés
authors.initials: A
authors.lastname: Piñeiro
authors.forename: Jesús
authors.initials: J
authors.lastname: Osada
mesh_terms: D000818:Animals; D016632:Apolipoprotein A-I / Q000097:blood / Q000235:genetics* / Q000276:immunology*; D053305:Apolipoprotein C-III; D001054:Apolipoproteins A / Q000097:blood / Q000235:genetics* / Q000276:immunology*; D001056:Apolipoproteins C / Q000097:blood / Q000235:genetics* / Q000276:immunology*; D015415:Biomarkers; D002784:Cholesterol / Q000097:blood; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D007249:Inflammation / Q000139:chemically induced / Q000235:genetics / Q000276:immunology; D007375:Interleukin-1 / Q000494:pharmacology; D015850:Interleukin-6 / Q000494:pharmacology; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D005810:Multigene Family / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D013552:Swine; D014280:Triglycerides / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D014425:Turpentine / Q000008:administration & dosage / Q000494:pharmacology
chemical_list: D016632:Apolipoprotein A-I; D053305:Apolipoprotein C-III; D001054:Apolipoproteins A; D001056:Apolipoproteins C; D015415:Biomarkers; D007375:Interleukin-1; D015850:Interleukin-6; D012333:RNA, Messenger; D014280:Triglycerides; D014409:Tumor Necrosis Factor-alpha; C022205:apolipoprotein A-IV; D002784:Cholesterol; D014425:Turpentine