Lv Zhou, Zhang Bohan, Zhang Hui, Mao Yanfei, Yu Qihong, Dong Wenwen
Department of Anesthesiology and Surgical Intensive Care Unit, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
Department of Gastroenterology, Changhai Hospital, The Second Military Medical University, Shanghai, China.
PeerJ. 2024 Dec 12;12:e18698. doi: 10.7717/peerj.18698. eCollection 2024.
AMD3100, a CXCR4 antagonist, has beneficial effects immaculate in the treatment of acute lung injury (ALI).
ALI is a severe inflammatory condition associated with poor prognosis and limited treatment options. AMD3100, has therapeutic effects that reduce ALI. Our study explored the regulatory mechanisms of AMD3100 in alleviating the injury of lipopolysaccharide (LPS)-induced ALI in mice.
Male ICR mice were randomly divided into control, LPS-treated, AMD3100-treated, and LPS + AMD3100-treatment groups. The histological changes of lung tissues from different groups were evaluated using hematoxylin and eosin staining. Lung injury was measured by ELISA and lung wet/dry ratio. Moreover, lung tissues from the four groups were subjected to transcriptome sequencing followed by differential expression, functional enrichment, protein-protein interaction (PPI) networks, and transcription factor analyses. The validation of mRNAs and protein levels were conducted with qRT-PCR and ELISA.
Hematoxylin and eosin staining combined with the concentration of IL-1 and IL1-β and lung wet/dry ratios revealed that AMD3100 reduced the level of LPS-induced lung injury. Analysis of the transcriptome sequencing data identified 294 differentially expressed genes in the LPS-induced ALI mouse model. Based on the PPI network and module analysis, hub targets of AMD3100, such as Cxcl10 and Cxcl9, were identified in module 1, and hub targets, such as Cxcl12 and Cxcl1, were identified in module 2. Cxcl10 and Cxcl9 are involved in the Toll-like receptor signaling pathway, and Cxcl12 and Cxcl1 arae enriched in the nuclear factor-kappa B signaling pathway. Cxcl19, Cxcl10, and Cxcl1 are targeted by transcription factors like NF-κB. The validation of mRNAs and protein levels conducted by PCR and ELISA supported our transcriptome data.
Our findings indicate that AMD3100 may exhibit a therapeutic effect on LPS-induced ALI in mice by modulating multiple chemokines to inhibit the Toll-like receptor/nuclear factor-kappa B signaling pathway.
AMD3100是一种CXCR4拮抗剂，在急性肺损伤（ALI）治疗中具有显著的有益作用。
ALI是一种严重的炎症性疾病，预后不良且治疗选择有限。AMD3100具有减轻ALI的治疗作用。本研究探讨了AMD3100减轻小鼠脂多糖（LPS）诱导的ALI损伤的调控机制。
将雄性ICR小鼠随机分为对照组、LPS处理组、AMD3100处理组和LPS + AMD3100处理组。采用苏木精-伊红染色评估不同组肺组织的组织学变化。通过ELISA和肺湿/干比测量肺损伤。此外，对四组肺组织进行转录组测序，随后进行差异表达、功能富集、蛋白质-蛋白质相互作用（PPI）网络和转录因子分析。用qRT-PCR和ELISA对mRNA和蛋白质水平进行验证。
苏木精-伊红染色结合IL-1和IL1-β浓度以及肺湿/干比显示，AMD3100降低了LPS诱导的肺损伤水平。对转录组测序数据的分析在LPS诱导的ALI小鼠模型中鉴定出294个差异表达基因。基于PPI网络和模块分析，在模块1中鉴定出AMD3100的枢纽靶点，如Cxcl10和Cxcl9，在模块2中鉴定出枢纽靶点，如Cxcl12和Cxcl1。Cxcl10和Cxcl9参与Toll样受体信号通路，Cxcl12和Cxcl1富集于核因子-κB信号通路。Cxcl19、Cxcl10和Cxcl1受NF-κB等转录因子靶向。PCR和ELISA对mRNA和蛋白质水平的验证支持了我们的转录组数据。
我们的研究结果表明，AMD3100可能通过调节多种趋化因子抑制Toll样受体/核因子-κB信号通路，对小鼠LPS诱导的ALI发挥治疗作用。
