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.