Serine Metabolism Supports Macrophage IL-1β Production. Author Arianne Rodriguez, Gregory Ducker, Leah Billingham, Carlos Martinez, Nello Mainolfi, Vipin Suri, Adam Friedman, Mark Manfredi, Samuel Weinberg, Joshua Rabinowitz, Navdeep Chandel Publication Year 2019 Type Journal Article Abstract Serine is a substrate for nucleotide, NADPH, and glutathione (GSH) synthesis. Previous studies in cancer cells and lymphocytes have shown that serine-dependent one-carbon units are necessary for nucleotide production to support proliferation. Presently, it is unknown whether serine metabolism impacts the function of non-proliferative cells, such as inflammatory macrophages. We find that in macrophages, serine is required for optimal lipopolysaccharide (LPS) induction of IL-1β mRNA expression, but not inflammasome activation. The mechanism involves a requirement for glycine, which is made from serine, to support macrophage GSH synthesis. Cell-permeable GSH, but not the one-carbon donor formate, rescues IL-1β mRNA expression. Pharmacological inhibition of de novo serine synthesis in vivo decreased LPS induction of IL-1β levels and improved survival in an LPS-driven model of sepsis in mice. Our study reveals that serine metabolism is necessary for GSH synthesis to support IL-1β cytokine production. Journal Cell Metab Volume 29 Issue 4 Pages 1003-1011.e4 Date Published 04/2019 ISSN Number 1932-7420 DOI 10.1016/j.cmet.2019.01.014 Alternate Journal Cell Metab. PMCID PMC6447453 PMID 30773464 PubMedPubMed CentralGoogle ScholarBibTeXEndNote X3 XML