期刊
CELL REPORTS
卷 32, 期 2, 页码 -出版社
CELL PRESS
DOI: 10.1016/j.celrep.2020.107881
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资金
- DRC Center Grant from the National Institutes of Health (NIH) [P30 DK063720]
- University of California, San Francisco (UCSF)
- Veterans Affairs Medical Center (VAMC) skeletal core facility
- NIH [P30 AR066262, U19CA179512, U19CA179513, R01HL133575]
- U.S. Department of Veterans Affairs Merit Award [1I01BX003928-01A2]
- American Heart Association [19POST34380672, 16GRNT27640007]
Developing strategies that promote the resolution of vascular inflammation and atherosclerosis remains a major therapeutic challenge. Here, we show that exosomes produced by naive bone marrow-derived macrophages (BMDM-exo) contain anti-inflammatory microRNA-99a/146b/378a that are further increased in exosomes produced by BMDM polarized with IL-4 (BMDM-IL-4-exo). These exosomal microRNAs suppress inflammation by targeting NF-kappa B and TNF-alpha signaling and foster M2 polarization in recipient macrophages. Repeated infusions of BMDM-IL-4-exo into Apoe(-)(/-) mice fed a Western diet reduce excessive hematopoiesis in the bone marrow and thereby the number of myeloid cells in the circulation and macrophages in aortic root lesions. This also leads to a reduction in necrotic lesion areas that collectively stabilize atheroma. Thus, BMDM-IL-4-exo may represent a useful therapeutic approach for atherosclerosis and other inflammatory disorders by targeting NF-kappa B and TNF-alpha via microRNA cargo delivery.
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