Immune-regulation of the apolipoprotein A-I/C-III/A-IV gene cluster in experimental inflammation.
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.
Navarro
María A
MA
Departamento de Bioquímica y Biología Molecular y Celular, Universidad de Zaragoza, Facultad de Veterinaria, Universidad de Zaragoza, Miguel Servet 177, E-50013 Zaragoza, Spain.
Carpintero
Rakel
R
Acín
Sergio
S
Arbonés-Mainar
Jose Miguel
JM
Calleja
Lucía
L
Carnicer
Ricardo
R
Surra
Joaquín C
JC
Guzmán-García
Mario A
MA
González-Ramón
Nieves
N
Iturralde
María
M
Lampreave
Fermín
F
Piñeiro
Andrés
A
Osada
Jesús
J
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
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