We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
SARS-CoV-2 N protein induced acute kidney injury in diabetic db/db mice is associated with a Mincle-dependent M1 macrophage activation.
- Authors
Wenjing Wu; Wenbiao Wang; Liying Liang; Junzhe Chen; Sifan Sun; Biao Wei; Yu Zhong; Xiao-Ru Huang; Jian Liu; Xiaoqin Wang; Xueqing Yu; Hui-Yao Lan
- Abstract
Cytokine storm" is common in critically ill COVID-19 patients, however, mechanisms remain largely unknown. Here, we reported that overexpression of SARS-CoV-2 N protein in diabetic db/db mice significantly increased tubular death and the release of HMGB1, one of the damage-associated molecular patterns (DAMPs), to trigger M1 proinflammatory macrophage activation and production of IL-6, TNF-α, and MCP-1 via a Mincle-Syk/NF-κB-dependent mechanism. This was further confirmed in vitro that overexpression of SARSCoV-2 N protein caused the release of HMGB1 from injured tubular cells under high AGE conditions, which resulted in M1 macrophage activation and production of proinflammatory cytokines via a Mincle-Syk/NF-κB-dependent mechanism. This was further evidenced by specifically silencing macrophage Mincle to block HMGB1-induced M1 macrophage activation and production of IL-6, TNF-α, and MCP-1 in vitro. Importantly, we also uncovered that treatment with quercetin largely improved SARS-CoV-2 N protein-induced AKI in db/db mice. Mechanistically, we found that quercetin treatment significantly inhibited the release of a DAMP molecule HMGB1 and inactivated M1 pro-inflammatory macrophage while promoting reparative M2 macrophage responses by suppressing Mincle-Syk/NF-κB signaling in vivo and in vitro. In conclusion, SARSCoV-2 N protein-induced AKI in db/db mice is associated with Mincledependent M1 macrophage activation. Inhibition of this pathway may be a mechanism through which quercetin inhibits COVID-19-associated AKI.
- Subjects
MACROPHAGE activation; QUERCETIN; ACUTE kidney failure; SARS-CoV-2; COVID-19; CYTOKINE release syndrome
- Publication
Frontiers in Immunology, 2023, p1
- ISSN
1664-3224
- Publication type
Article
- DOI
10.3389/fimmu.2023.1264447