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| Status |
Public on Jul 14, 2021 |
| Title |
MYC-mediated early glycolysis negatively regulates proinflammatory responses by controlling IRF4 in inflammatory macrophages |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
MYC activates different metabolic programs in a cell-type and cell-status dependent manner. However, the role of MYC in inflammatory macrophages has not yet been determined. Metabolic and molecular analyses reveal that MYC, but not HIF1, is involved in enhancing early glycolytic flux during inflammatory macrophage polarization. Ablation of MYC decreases lactate production by regulating lactate dehydrogenase (LDH) activity and causes increased inflammatory cytokines by regulating interferon regulatory factor 4 (IRF4) in response to lipopolysaccharide (LPS). Moreover, myeloid-specific deletion of MYC and pharmacological inhibition of MYC/LDH axis enhance inflammation and the bacterial clearance in vivo. These results elucidate the potential role of the MYC/LDH/IRF4 axis in inflammatory macrophages by connecting early glycolysis and inflammatory responses and suggest that modulating early glycolytic flux mediated by the MYC/LDH axis can be utilized to open new avenues for the therapeutic modulation of macrophage polarization to fight against bacterial infection.
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| Overall design |
For the generation BMDMs, bone marrow cells were flushed from femurs and tibias of mice and cultured at 37oC, 5% CO2 in complete α-MEM medium (10% heat-inactivated defined FBS (HyClone Fisher), penicillin-streptomycin (Invitrogen), and L-glutamine (Invitrogen)) with 5% L929 cell supernatant as conditioned medium (CM) as a source of M-CSF (Englen et al., 1995) after lysis of RBCs using ACK lysis buffer (Invitrogen). Then, the non-adherent cell population was recovered the next day and cultured for three additional days. Final concentration of M-CSF in our culture was 23.3 ng/ml. Cells that remained in suspension were removed by aspiration and attached cells were washed twice with PBS, then re-plated and cultured with complete α-MEM medium with 20 ng/ml human M-CSF. Cells were stimulated with LPS (10ng/ml) for 3 hours.
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| Contributor(s) |
Park-Min K |
| Citation(s) |
34133930 |
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| Submission date |
Jan 08, 2021 |
| Last update date |
Jul 14, 2021 |
| Contact name |
Kyung-Hyun Park-Min |
| E-mail(s) |
ParkminK@HSS.EDU, parkmink@gmail.com
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| Organization name |
Hospital for Special Surgery
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| Street address |
535 East 70th Street
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| City |
New York |
| State/province |
NY |
| ZIP/Postal code |
10021 |
| Country |
USA |
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| Platforms (2) |
| GPL15103 |
Illumina HiSeq 1000 (Mus musculus) |
| GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
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| Samples (8)
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| Relations |
| BioProject |
PRJNA690806 |
| SRA |
SRP300921 |
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