Suppression of overactivated immunity in the early stage is the key to improve the prognosis in severe burns

作者：Yang Xiang, Bohan Pan, Jin Zhang, Ji-Qiu Chen, Fang He, Qun Wang, Linhui Li, Tiansheng Chen, Jiaxin Chen, Chan Li, Xingfeng Zheng, Shihui Zhu · 发表于：Frontiers in Immunology · 年份：2024 · DOI：10.3389/fimmu.2024.1455899 · 被引用次数：7 · 研究领域：S100 Proteins and Annexins、Burn Injury Management and Outcomes、Immune Response and Inflammation

Background: Severe burns can lead to systemic inflammatory response syndrome (SIRS) and multiple organ dysfunction syndrome (MODS) due to inflammation-immunity dysregulation. This study aimed to identify key immune-related molecules and potential drugs for immune regulation in severe burn treatment. Method: Microarray datasets GSE77791 and GSE37069 were analyzed to identify immune-related differentially expressed genes (DEGs), enriched pathways and prognosis-related genes. The DGIdb database was used to identify potentially clinically relevant small molecular drugs for hub DEGs. Hub DEGs were validated by total RNA from clinical blood samples through qPCR. The efficacy of drug candidates was tested in a severe burn mouse model. Pathologic staining was used to observe organ damage. Enzyme Linked Immunosorbent Assay (ELISA) was used to detect the serum IL-1b, IL-6, TNF-a and MCP-1 contents. Activation of the NF-κB inflammatory pathway was detected by western blotting. Transcriptome sequencing was used to observe inflammatory-immune responses in the lung. Results: A total of 113 immune-related DEGs were identified, and the presence of immune overactivation was confirmed in severe burns. S100A8 was not only significantly upregulated and identified to be prognosis-related among the hub DEGs but also exhibited an increasing trend in clinical blood samples. Methotrexate, which targets S100A8, as predicted by the DGIdb, significantly reduces transcription level of S100A8 and inflamma...