Effects of apoE genotype on macrophage inflammation and heme oxygenase-1 expression.
In order to gain a more comprehensive understanding of the aetiology of apolipoprotein E4 genotype-cardiovascular disease (CVD) associations, the impact of the apoE genotype on the macrophage inflammatory response was examined. The murine monocyte-macrophage cell line (RAW 264.7) stably transfected to produce equal amounts of human apoE3 or apoE4 was used. Following LPS stimulation, apoE4-macrophages showed higher and lower concentrations of tumour necrosis factor alpha (pro-inflammatory) and interleukin 10 (anti-inflammatory), respectively, both at mRNA and protein levels. In addition, increased expression of heme oxygenase-1 (a stress-induced anti-inflammatory protein) was observed in the apoE4-cells. Furthermore, in apoE4-macrophages, an enhanced transactivation of the key redox sensitive transcription factor NF-kappaB was shown. Current data indicate that apoE4 macrophages have an altered inflammatory response, which may contribute to the higher CVD risk observed in apoE4 carriers.
Jofre-Monseny
Laia
L
Institute of Human Nutrition and Food Science, Christian Albrechts University of Kiel, Hermann-Rodewald-Strasse 6, 24098 Kiel, Germany.
Loboda
Agnieszka
A
Wagner
Anika E
AE
Huebbe
Patricia
P
Boesch-Saadatmandi
Christine
C
Jozkowicz
Alicja
A
Minihane
Anne-Marie
AM
Dulak
Jozef
J
Rimbach
Gerald
G
D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics / Q000276:immunology*; D002460:Cell Line; D005838:Genotype; D051547:Heme Oxygenase-1 / Q000276:immunology*; D007249:Inflammation / Q000276:immunology*; D008262:Macrophage Activation / Q000276:immunology*; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D018384:Oxidative Stress / Q000276:immunology; D017382:Reactive Oxygen Species / Q000276:immunology*
D001057:Apolipoproteins E; D017382:Reactive Oxygen Species; D051547:Heme Oxygenase-1