Notch1 Signaling Pathway Mediates Monocyte Dysfunction and Exacerbates Persistent Inflammation After Burn Injury
10.3870/j.issn.1672-0741.24.09.013
- VernacularTitle:Notch1信号通路介导单核细胞功能障碍加重烧伤后持续炎症
- Author:
Shan GAO
1
;
Yanqiong XIA
1
;
Leilei YANG
1
Author Information
1. 武汉市第三医院(武汉大学同仁医院)麻醉科,武汉 430060
- Publication Type:Journal Article
- Keywords:
burn;
persistent inflammation;
immunosuppression;
monocyte;
Notch1 signaling pathway
- From:
Acta Medicinae Universitatis Scientiae et Technologiae Huazhong
2025;54(3):335-342
- CountryChina
- Language:Chinese
-
Abstract:
Objective To analyze the expression of monocyte surface antigen-presenting factors CD86+and HLA-DR in the subacute phase of burn injury,and the molecular mechanism of monocytes contributing to persistent inflammation.Methods The mice were divided into the sham group and the burn group,and a mouse model of 30％body surface burn was estab-lished.Spleens were collected from mice on the 8th day after burn injury,and monocytes were isolated for transcriptomic analy-sis.A mouse model of Notch1 lentiviral transfection was constructed,and models of sham burn+blank control(sham-NC),burn+blank control(burn-NC),sham burn+Notch1 shRNA(sham-sh),and burn+Notch1 shRNA(burn-sh)were estab-lished.The qRT-PCR and Western blot were used to detect the expressions of monocyte surface antigens CD86+and HLA-DR.Immunofluorescence was performed to analyze the expression of CD86+and HLA-DR in splenic monocytes.ELISA was used to analyze serum levels of IL-10 and CRP.Results On the 8th day after burn injury,compared with the sham burn group,the expressions of monocyte surface antigens CD86+and HLA-DR were decreased,while serum levels of IL-10 and CRP were increased in the burn group.Contents of IL-10 and CRP showed significant negative correlations with CD86+and HLA-DR,re-spectively.Transcriptomic analysis revealed 258 significantly upregulated genes and 360 significantly downregulated genes in splenic monocytes from the burn group.The differentially expressed genes primarily enriched in the Notch signaling path-way.Western blot results showed a significant upregulation of Notch1 expression.After lentiviral inhibition of Notch1 signaling invivo,compared with the burn-NC group,expressions of CD86+and HLA-DR on monocyte surfaces were increased,and ser-um levels of IL-10 and CRP were decreased in the burn-sh group.Conclusion The functional inhibition of splenic monocytes is mediated by Notch1 signaling pathway in the subacute phase of burn injury.Inhibition of Notch1 signaling in vivo improves the antigen-presenting capacity of monocytes after burn injury and inhibits the secretion of inflammatory factors.
