{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T23:54:48Z","timestamp":1785801288283,"version":"3.56.0"},"reference-count":46,"publisher":"American Physiological Society","issue":"17","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Physiological Genomics"],"published-print":{"date-parts":[[2014,9,1]]},"abstract":"<jats:p>S-adenosylmethionine (SAM), the unique methyl donor in DNA methylation, has been shown to lower lipopolysaccharide (LPS)-induced expression of the proinflammatory cytokine TNF-\u03b1 and increase the expression of the anti-inflammatory cytokine IL-10 in macrophages. The aim of this study was to assess whether epigenetic mechanisms mediate the anti-inflammatory effects of SAM. Human monocytic THP1 cells were differentiated into macrophages and treated with 0, 500, or 1,000 \u03bcmol\/l SAM for 24 h, followed by stimulation with LPS. TNF\u03b1 and IL-10 expression levels were measured by real-time PCR, cellular concentrations of SAM and S-adenosylhomocysteine (SAH), a metabolite of SAM, were measured by liquid chromatography-tandem mass spectrometry (LC-MS\/MS), and DNA methylation was measured with LC-MS\/MS and microarrays. Relative to control (0 \u03bcmol\/l SAM), treatment with 500 \u03bcmol\/l SAM caused a significant decrease in TNF-\u03b1 expression (\u221245%, P &lt; 0.05) and increase in IL-10 expression (+77%, P &lt; 0.05). Treatment with 1,000 \u03bcmol\/l SAM yielded no significant additional benefits. Relative to control, 500 \u03bcmol\/l SAM increased cellular SAM concentrations twofold without changes in SAH, and 1,000 \u03bcmol\/l SAM increased cellular SAM sixfold and SAH fourfold. Global DNA methylation increased 7% with 500 \u03bcmol\/l SAM compared with control. Following treatment with 500 \u03bcmol\/l SAM, DNA methylation microarray analysis identified 765 differentially methylated regions associated with 918 genes. Pathway analysis of these genes identified a biological network associated with cardiovascular disease, including a subset of genes that were differentially hypomethylated and whose expression levels were altered by SAM. Our data indicate that SAM modulates the expression of inflammatory genes in association with changes in specific gene promoter DNA methylation.<\/jats:p>","DOI":"10.1152\/physiolgenomics.00056.2014","type":"journal-article","created":{"date-parts":[[2014,7,16]],"date-time":"2014-07-16T10:14:27Z","timestamp":1405505667000},"page":"617-623","source":"Crossref","is-referenced-by-count":85,"title":["S-adenosylmethionine mediates inhibition of inflammatory response and changes in DNA methylation in human macrophages"],"prefix":"10.1152","volume":"46","author":[{"given":"Anna C.","family":"Pfalzer","sequence":"first","affiliation":[{"name":"Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, Massachusetts; and"},{"name":"Friedman School of Nutrition Science and Policy, Tufts University, Boston, Massachusetts, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sang-Woon","family":"Choi","sequence":"additional","affiliation":[{"name":"Jean 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