Methionine Attenuates Lipopolysaccharide-Induced Inflammatory Responses via DNA Methylation in Macrophages

Abstract

-adenosylmethionine (SAM), the methyl donor for DNA methylation, which has an important role in the inflammatory responses. However, whether Met exerts anti-inflammatory effects by altering DNA methylation in macrophages is unclear. In this study, Met was found to diminish the activation of the mitogen-activated protein kinase signaling pathway; decrease the production of tumor necrosis factor-α, interleukin-6, and interferon-β; and enhance the levels of intracellular SAM after lipopolysaccharide (LPS) treatment in macrophages. Similarly, SAM inhibited the LPS-induced inflammatory response, consistent with the result of Met treatment. Met-treated macrophages displayed increased global DNA methylation. The DNA methyltransferase inhibitor 5-aza-2'-deoxycytidine partially blocked the anti-inflammatory effects of Met in macrophages, suggesting a mechanism involving DNA methylation. Collectively, the results indicated that Met inhibits the LPS-induced inflammatory response by altering DNA methylation in RAW 264.7 macrophages. The findings provide new insights into the interplay between nutrition and immunology, and highlight the regulatory effects of amino acids on the host immune system.