|
| Status |
Public on Oct 01, 2021 |
| Title |
Identification of pharmacologic inhibitors and activators of IL-4-induced macrophage polarization |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Macrophages polarize towards different subpopulations with distinct and partly antagonistic functions in various diseases. IFNγ/LPS-polarized M1-type macrophages can have antiangiogenic activity, whereas IL-4-induced M2-type macrophages can be proangiogenic and profibrotic. Therapeutic strategies to inhibit M2-type polarization while promoting M1-type polarization could serve to inhibit pathological angiogenesis and fibrosis. Here, by combining global quantitative time-course proteomics and phosphoproteomics with a small-molecule inhibitor screen we identify signaling events that promote specifically IL-4-induced and not IFNγ/LPS-induced macrophage polarization and found that the MEK inhibitor trametinib and the HDAC inhibitor panobinostat potently prevent M2-type macrophage polarization without inhibiting M1-type polarization. In contrast, selective B-Raf inhibition promotes M2-type polarization. Trametinib and panobinostat also blocked M2-type macrophage polarization and concomitantly angiogenesis and fibrosis in models of wound healing and neovascular age-related macular degeneration in vivo. Thus, these pharmacologic inhibitors could be utilized therapeutically to selectively block IL4-induced macrophage polarization and reduce pathologic angiogenesis and fibrosis.
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| |
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| Overall design |
THP-1 cell M1-type and M2-type polarizations
|
| |
|
| Contributor(s) |
He L, Marneros AG |
| Citation(s) |
34731634 |
| Submission date |
Nov 12, 2019 |
| Last update date |
Dec 31, 2021 |
| Contact name |
Alexander G Marneros |
| E-mail(s) |
amarneros@mgh.harvard.edu
|
| Organization name |
Massachusetts General Hospital, Harvard Medical School
|
| Department |
Department of Dermatology, Cutaneous Biology Research Center
|
| Street address |
13th Street
|
| City |
Charlestown |
| State/province |
MA |
| ZIP/Postal code |
02129 |
| Country |
USA |
| |
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| Platforms (1) |
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| Samples (12)
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| Relations |
| BioProject |
PRJNA589025 |
| SRA |
SRP229593 |
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