期刊
CELL METABOLISM
卷 29, 期 4, 页码 1003-+出版社
CELL PRESS
DOI: 10.1016/j.cmet.2019.01.014
关键词
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资金
- NIH [5P01AG049665, 5P01HL071643, 5T32HL076139-15, 5DP1DK113643-03]
- Ford Foundation
- NCI [K99 CA215307]
- Cancer Center Support Grant [NCI CA060553]
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-1 beta 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-1 beta mRNA expression. Pharmacological inhibition of de novo serine synthesis in vivo decreased LPS induction of IL-1 beta 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-1 beta cytokine production.
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