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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Jan 15, 2019 |
| Title |
Serine metabolism supports macrophage IL-1β production. |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Serine is a substrate for nucleotides, 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 glutathione (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.
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| Overall design |
BMDMs,were,cultured,in,complete,MEM,,MEM,without,serine,,MEM,with,100ng/mL,LPS,,MEM,without,serine,but,with,100ng/mL,LPS,
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| Contributor(s) |
Rodriguez AE, Ducker GS, Billingham LK, Martinez CA, Mainolfi N, Suri V, Friedman A, Manfredi MG, Weinberg SE, Rabinowitz JD, Chandel NS |
| Citation(s) |
30773464 |
| NIH grant(s) |
| Grant ID |
Grant title |
Affiliation |
Name |
| P01 AG049665 |
Modulating mitochondrial function to promote proteostasis in the aging lung |
NORTHWESTERN UNIVERSITY AT CHICAGO |
NAVDEEP S CHANDEL |
| P01 HL071643 |
Metabolic Regulation of Acute Lung Injury |
NORTHWESTERN UNIVERSITY AT CHICAGO |
NAVDEEP S CHANDEL |
| T32 HL076139 |
Training Program In Lung Sciences |
NORTHWESTERN UNIVERSITY AT CHICAGO |
KAREN M RIDGE |
| DP1 DK113643 |
Metabolism in Action: Quantitative Fluxes in Mammals |
PRINCETON UNIVERSITY |
JOSHUA D RABINOWITZ |
| K99 CA215307 |
Glycine metabolism in cancer |
PRINCETON UNIVERSITY |
Gregory S Ducker |
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| Submission date |
Jan 14, 2019 |
| Last update date |
Apr 16, 2019 |
| Contact name |
Navdeep Chandel |
| E-mail(s) |
nav@northwestern.edu
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| Organization name |
Northwestern University
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| Department |
Pulmonary and Critical Care
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| Street address |
303 E Superior St, SQ5
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| City |
Chicago |
| State/province |
IL |
| ZIP/Postal code |
60611 |
| Country |
USA |
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| Platforms (1) |
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| Samples (16)
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| Relations |
| BioProject |
PRJNA515004 |
| SRA |
SRP179044 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE125036_Control_LPS_vs_Dropout_LPS_BM.htseq.edgeR.txt.gz |
1.6 Mb |
(ftp)(http) |
TXT |
| GSE125036_Control_untreated_vs_Dropout_LPS_BM.htseq.edgeR.txt.gz |
1.7 Mb |
(ftp)(http) |
TXT |
| GSE125036_Control_untreated_vs_Dropout_untreated_BM.htseq.edgeR.txt.gz |
1.6 Mb |
(ftp)(http) |
TXT |
| GSE125036_Control_untreated_vs_LPS_BM.htseq.edgeR.txt.gz |
1.7 Mb |
(ftp)(http) |
TXT |
| GSE125036_Dropout_untreated_vs_LPS_BM.htseq.edgeR.txt.gz |
1.7 Mb |
(ftp)(http) |
TXT |
| GSE125036_htseq.all.counts.txt.gz |
1.6 Mb |
(ftp)(http) |
TXT |
| GSE125036_htseq.fpkms.txt.gz |
5.4 Mb |
(ftp)(http) |
TXT |
| GSE125036_htseq.normCounts.txt.gz |
4.8 Mb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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