Fatty acids (FAs) are known to participate in body inflammatory responses. In particular, saturated FAs such as palmitic acid (PA) induce inflammatory signals in macrophages, whereas polyunsaturated FAs, including docosahexaenoic acid (DHA), have been related to anti-inflammatory effects. Several studies have suggested a role of fatty acids on DNA methylation, epigenetically regulating gene expression in inflammation processes. Therefore, this study investigated the effect of PA and DHA on the inflammation-related genes on human macrophages. In addition, a second aim was to study the epigenetic mechanism underlying the effect of FAs on the inflammatory response. For these purposes, human acute monocytic leukaemia cells (THP-1) were differentiated into macrophages with 12-O-tetradecanoylphorbol-13-acetate (TPA), followed by an incubation with PA or DHA. At the end of the experiment, mRNA expression, protein secretion, and CpG methylation of the following inflammatory genes were analysed: interleukin 1 beta (IL1B), tumour necrosis factor (TNF), plasminogen activator inhibitor-1 (SERPINE1) and interleukin 18 (IL18). The results showed that the treatment with PA increased IL-18 and TNF-α production. Contrariwise, the supplementation with DHA reduced IL-18, TNF-α and PAI-1 secretion by macrophages. However, the incubation with these fatty acids did not apparently modify the DNA methylation status of the investigated genes in the screened CpG sites. This research reveals that PA induces important pro-inflammatory markers in human macrophages, whereas DHA decreases the inflammatory response. Apparently, DNA methylation is not directly involved in the fatty acid-mediated regulation of the expression of these inflammation-related genes.

中文翻译：

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棕榈酸和DHA处理后与炎症相关的基因调控不是由DNA甲基化介导的。

已知脂肪酸（FAs）参与人体炎症反应。特别地，诸如棕榈酸（PA）的饱和FA在巨噬细胞中诱导炎症信号，而包括二十二碳六烯酸（DHA）在内的多不饱和FA与抗炎作用有关。多项研究表明，脂肪酸在DNA甲基化中起着表观遗传的作用，调节炎症过程中的基因表达。因此，本研究调查了PA和DHA对人类巨噬细胞炎症相关基因的影响。另外，第二个目的是研究FA对炎症反应的影响的表观遗传机制。为此，将人类急性单核细胞白血病细胞（THP-1）与12-O-十四烷酰phorbol-13-乙酸盐（TPA）分化为巨噬细胞，然后与PA或DHA孵育。在实验结束时，分析了以下炎症基因的mRNA表达，蛋白质分泌和CpG甲基化：白介素1β（IL1B），肿瘤坏死因子（TNF），纤溶酶原激活物抑制剂1（SERPINE1）和白介素18（IL18）。结果表明，用PA处理增加了IL-18和TNF-α的产生。相反，补充DHA可减少巨噬细胞的IL-18，TNF-α和PAI-1分泌。然而，与这些脂肪酸的温育显然没有改变所筛选的CpG位点中所研究基因的DNA甲基化状态。这项研究表明，PA可以诱导人巨噬细胞中重要的促炎标记，而DHA可以降低炎症反应。显然，DNA甲基化并不直接参与脂肪酸介导的这些炎症相关基因表达的调节。