ApoE Production in Human Monocytes and Its Regulation by Inflammatory Cytokines

作者：Braesch Andersen Sten^*; Paulie Staffan; Smedman Christian; Mia Sohel; Kumagai Braesch Makiko

来源：PLos One, 2013, 8(11): e79908.

DOI：10.1371/journal.pone.0079908

The apoE production by tissue macrophages is crucial for the prevention of atherosclerosis and the aim of this study was to further elucidate how this apolipoprotein is regulated by cytokines present during inflammation. Here we studied apoE production in peripheral blood mononuclear cells (PBMC) and analysis was made with a newly developed apoE ELISpot assay. In PBMC, apoE secretion was restricted to monocytes with classical (CD14(++) CD16(-)) and intermediate (CD14(+) CD16(+)) monocytes being the main producers. As earlier described for macrophages, production was strongly upregulated by TGF-beta and downregulated by bacterial lipopolysaccharide (LPS) and the inflammatory cytokines IFN-gamma, TNF-alpha and IL-1 beta. We could here show that a similar down-regulatory effect was also observed with the type I interferon, IFN-alpha, while IL-6, often regarded as one of the more prominent inflammatory cytokines, did not affect TGF-beta-induced apoE production. The TNF-alpha inhibitor Enbrel could partly block the down-regulatory effect of IFN-gamma, IFN-alpha and IL-1 beta, indicating that inhibition of apoE by these cytokines may be dependent on or synergize with TNF-alpha. Other cytokines tested, IL-2, IL-4, IL-12, IL-13, IL-17A and IL23, had no inhibitory effect on apoE production. In contrast to the effect on monocytes, apoE production by primary hepatocytes and the hepatoma cell line HepG2 was more or less unaffected by treatment with cytokines or LPS.

• 出版日期2013-11-14