Folic Acid Improves the Inflammatory Response in LPS-Activated THP-1 Macrophages

DNA methylation has been suggested as a regulatory mechanism behind some inflammatory processes. The physiological actions of methyl donors, such as folic acid, choline, and vitamin B(12) on inflammation-related disease have been associated with the synthesis of the universal methyl donor S-adenosyl methionine (SAM). The aim of this study was to evaluate the effects of folic acid, choline, vitamin B(12), and a combination of all on preventing the lipopolysaccharide- (LPS-) induced inflammatory response in human THP-1 monocyte/macrophage cells. Folic acid and the mixture of methyl donors reduced interleukin 1 beta (IL1B) and tumour necrosis factor (TNF) expression as well as protein secretion by these cells. Folic acid and choline decreased C-C motif chemokine ligand 2 (CCL2) mRNA levels. In addition to this, the methyl donor mixture reduced Cluster of differentiation 40 (CD40) expression, but increased serpin family E member 1 (SERPINE1) expression. All methyl donors increased methylation levels in CpGs located in IL1B, SERPINE1, and interleukin 18 (IL18) genes. However, TNF methylation was not modified. After treatment with folic acid and the methyl donor mixture, ChIP analysis showed no change in the binding affinity of nuclear factor-κB (NF-κB) to IL1B and TNF promoter regions after the treatment with folic acid and the methyl donor mixture. The findings of this study suggest that folic acid might contribute to the control of chronic inflammation in inflammatory-related disease.