期刊
SCIENTIFIC REPORTS
卷 6, 期 -, 页码 -出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/srep31873
关键词
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资金
- Rosetrees Trust [M137-M1]
- Academy of Medical Sciences
- National Eye Research Centre (NERC)
- Fight for Sight PhD studentship [1395/96]
- China Scholarship Council (CSC) studentship
- MRC [MR/N027086/1, MR/J015350/1] Funding Source: UKRI
- Academy of Medical Sciences (AMS) [AMS-SGCL10-Liu] Funding Source: researchfish
- British Heart Foundation [SP/12/7/29572] Funding Source: researchfish
- Fight for Sight [1395/96] Funding Source: researchfish
- Medical Research Council [MR/N027086/1, MR/J015350/1] Funding Source: researchfish
- National Institute for Health Research [CL-2012-25-002] Funding Source: researchfish
- Rosetrees Trust [M137-F1] Funding Source: researchfish
- The Dunhill Medical Trust [R138/1109] Funding Source: researchfish
There is an integral relationship between vascular cells and leukocytes in supporting healthy tissue homeostasis. Furthermore, activation of these two cellular components is key for tissue repair following injury. Toll-like receptors (TLRs) play a role in innate immunity defending the organism against infection, but their contribution to angiogenesis remains unclear. Here we used synthetic TLR9 agonists, cytosine-phosphate-guanosine oligodeoxynucleotides (CpG-ODN), to investigate the role of TLR9 in vascular pathophysiology and identify potential therapeutic translation. We demonstrate that CpG-ODN stimulates inflammation yet inhibits angiogenesis. Regulation of angiogenesis by CpG-ODN is pervasive and tissue non-specific. Further, we noted that synthetic CpG-ODN requires backbone phosphorothioate but not TLR9 activation to render and maintain endothelial stalk cells quiescent. CpG-ODN pre-treated endothelial cells enhance macrophage migration but restrain pericyte mobilisation. CpG-ODN attenuation of angiogenesis, however, remains TLR9-dependent, as inhibition is lost in TLR9 deficient mice. Additionally, CpG-ODNs induce an M1 macrophage phenotype that restricts angiogenesis. The effects mediated by CpG-ODNs can therefore modulate both endothelial cells and macrophages through distinct pathways, providing potential therapeutic application in ocular vascular disease.
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