期刊
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
卷 546, 期 -, 页码 97-102出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2021.01.104
关键词
Aging; Spike-protein; COVID-19; Inflammation; Macrophages; Senescence; Cathepsins
资金
- Nova Southeastern University President Faculty Research Development Grant [PFRDG-334846]
- NIH [R01AG-0640 03, R15DE-028699, R03DE-027153]
The Spike protein of SARS-CoV-2 virus can increase the production of SASP markers in macrophages, with varying effects based on age and gender, as shown in a mouse model of M-CSF and IL-34-differentiated macrophages.
The SARS-CoV-2 virus causes elevated production of senescence-associated secretory phenotype (SASP) markers by macrophages. SARS-CoV-2 enters macrophages through its Spike-protein aided by cathepsin (Cat) B and L, which also mediate SASP production. Since M-CSF and IL-34 control macrophage differentiation, we investigated the age-dependent effects of the Spike-protein on SASP-related pro-inflammatory-cytokines and nuclear-senescence-regulatory-factors, and CatB, L and K, in mouse M-CSFand IL-34-differentiated macrophages. The Spike-protein upregulated SASP expression in young and aged male M-CSF-macrophages. In contrast, only young and aged male IL-34-macrophages demonstrated significantly reduced pro-inflammatory cytokine expression in response to the Spike-protein in vitro. Furthermore, the S-protein elevated CatB expression in young male M-CSF-macrophages and young female IL-34-macrophages, whereas CatL was overexpressed in young male IL -34and old male M-CSF macrophages. Surprisingly, the S-protein increased CatK activity in young and aged male M-CSF macrophages, indicating that CatK may be also involved in the COVID-19 pathology. Altogether, we demonstrated the ageand sex-dependent effects of the Spike-protein on M-CSF and IL-34-macrophages using a novel in vitro mouse model of SARS-CoV-2/COVID-19. (c) 2021 Elsevier Inc. All rights reserved.
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