Abstract
S‐adenosylmethionine (SAM), the unique methyl donor in DNA methylation, has been shown to lower inflammation. To assess whether epigenetic mechanisms mediate this effect, THP‐1 cells were differentiated into macrophages and treated with 0 μmol/L, 500 μmol/L(low), or 1000 μmol/L (high) SAM for 24‐hours, followed by stimulation with LPS. TNFα and IL‐10 expression levels were measured using RT‐PCR. Cellular SAM and S‐adenosylhomocysteine (SAH), a metabolite of SAM, were measured by LC/MS/MS. DNA methylation was measured using LC/MS/MS and microarrays.Relative to 0 μmol/L SAM, treatment with low SAM caused a significant decrease in TNFα expression (−45%, p<0.05) and increase in IL‐10 expression (+77%, p<0.05). Treatment with high SAM yielded no significant additional benefits. Relative to 0 μmol/L SAM, low SAM treatment increased cellular SAM concentrations 2‐fold (56 nmol/mg vs 90 nmol/mg) without changes in SAH. Treatment with high SAM increased cellular SAM 6‐fold (330 nmol/mg) and SAH 4‐fold (2.1 nmol/mg vs 9.2 nmol/mg) relative to control. Genomic DNA methylation was significantly increased from 4.5% to 4.8% (p<0.05) only by treatment with low SAM. Microarrays identified 765 differentially methylated regions.SAM exerts significant anti‐inflammatory effects through modulation of gene expression, possibly mediated by DNA methylation.Funded by USDA ARS contract#1950–51000‐072 and by Pharmavite LLCGrant Funding Source: USDA ARS contract #1950–51000‐072 and Pharmavite LLC
Published Version
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