Serine Metabolism Supports Macrophage IL-1β Production

Arianne E. Rodriguez, Gregory S. Ducker, Leah K. Billingham, Carlos A. Martinez, Nello Mainolfi, Vipin Suri, Adam Friedman, Mark G. Manfredi, Samuel E. Weinberg, Joshua D. Rabinowitz, Navdeep S. Chandel*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

124 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)1003-1011.e4
JournalCell Metabolism
Issue number4
StatePublished - Apr 2 2019


  • IL-1beta
  • LPS response
  • glutathione
  • immunometabolism
  • inflammation
  • macrophage
  • one-carbon metabolism
  • sepsis
  • serine metabolism

ASJC Scopus subject areas

  • Molecular Biology
  • Physiology
  • Cell Biology


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