Role of NLRP3/SDF-1 Signaling Pathway in the Treatment of Asthma with Budesonide
Objective To explore the mechanism of NLRP3/SDF-1 signaling in the inflammatory process of asthmatic airways. Methods Thirty-six 4-week-old male BALB/c mice were randomly divided into control group,asthma group and budesonide (BUD)group,with 12 mice in each group. A mouse asthma model was constructed by intraperitoneal injection of ovalbumin (OVA). H-E staining was used to observe lung tissue lesions,and the number of inflammatory cells in alveolar lavage fluid (BALF)was counted. Western-blot was used to detect the protein expression levels of NLRP3,SDF-1 and CXCR4 in lung tissue. BEAS-2B/sh NLRP3 cell line was constructed by using lentivirus,CCK-8 was used to detect cell proliferation activity. Different concentrations (0,200,400,800 U/mL)of house dust mite (HDM) were used to treat cells and simulate aninvitro asthma model. The NLRP3,p-NF-κB and SDF-1 protein expression levels were compared in NLRP3 inhibitor (MCC950)alone and in combination with BUD treat-ment. Results (1)Inflammatory cell counts:increased in the asthma group compared to the control group (P<0.001),while decreased in the BUD group compared to the asthma group (P<0.001). (2)Protein expression levels of NLRP3,SDF-1 and CXCR4 in mouse lung tissue:the asthma group showed an increase in all three indicators compared to the control group (P<0.001,P<0.01 and P<0.001),while the BUD group showed a decrease compared to the asthma group (P<0.001 ). (3)Protein expression levels of NLRP3,p-NF-κB and SDF-1 in cells:The p-NF-κB expression levels in HDM (400 U/mL)and HDM (800 U/mL)groups were higher than that in the control group (P<0.05, P<0.01). After HDM intervention,the p-NF-κB level of cells in BEAS-2B/sh NLRP3 group decreased (P<0.01,P<0.01 and P<0.001),and the SDF-1 protein had the same trend as the p-NF-κB protein. Compared with the group treated with MCC950 alone,the combined treatment of MCC950 and BUD resul-ted in a decrease in protein expression of all three indicators (P<0.05,P<0.05 and P<0.01 ). Conclusion BUD can inhibit asthma by limiting the NLRP3/SDF-1 signaling,and the combination of BUD and NLRP3 inhibitors may be a treatment strategy for asthma.
万方数据
维普
