BMSCs inhibit inflammation in mice with LPS-induced acute lung injury by regulating TLR4/MyD88/NF-κB signaling pathway

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Authors:Chen Maoqiong ,Yang Mengting, Cai Jiao, Kuang Menglan, Wu Sha, Yang Shanfu, Zhang Zhinan, Yang Xiaojun,Fan Yongxia

Keywords:acute lung injury;mice;bone marrow mesenchymal stem cells;TLR4/MyD88/NF-κB signaling pathway;inflammatory response

DOI:10.19405/j.cnki.issn1000-1492.2023.12.013

〔Abstract〕 Objective To investigate the effect of bone marrow mesenchymal stem cells(BMSCs) on the inflammatory response of lipopolysaccharide(LPS) induced acute lung injury(ALI) in mice. Methods 32 SPF KM mice, aged 4 weeks were randomly divided into four groups, control group, LPS group, dexamethasone treatment group(LPS+DEX) and BMSCs treatment group(LPS+BMSCs). The latter three groups were injected with LPS by tracheal puncture to establish mouse ALI model 24 h after modeling, BMSCs isolated from the femur of mice were injected into the caudal vein, and DEX were injected into caudal vein at the same time in LPS+DEX group for 3 consecutive days. On the 4th day after cell transplantation or 24 h after DEX injection, the survival quantity of mice was recorded, lung function was detected, and the wet/dry weight ratio(W/D) of lung was measured. Then inflammatory cells in bronchoalveolar lavage fluid(BALF), lung pathological changes and serum inflammatory cytokines were collected. Green fluorescent protein(GFP) staining was used to observe the homing of BMSCs in lung tissues. The mRNA and protein expression of TLR4, MyD88 and NF-κB in lung tissues were detected by RT-PCR and Western blot assay respectively. Results Compared with the control group, LPS model group showed decreased lung function, significantly increase in the W/D weight ratio of lung, inflammatory cytokines in serum and inflammatory cells in BALF, and severe damage in lung tissue. Compared with LPS group, LPS+DEX group and LPS+BMSCs group showed improved lung function, reduced lung tissue damage, significantly decrease in the W/D weight ratio of lung, inflammatory cytokines in serum and inflammatory cells in BALF. And the expression of TLR4-MyD88-NF-κB signaling pathway-related genes and proteins decreased, the survival quantity increased. Conclusion Homologous BMSCs transplantation can effectively treat LPS-induced acute lung injury, and the mechanism may be related to the regulation of TLR4-MyD88-NF-κB signaling pathway and the reduction of inflammatory response. These findings provide the experimental basis for BMSCs homologous transplantation for ALI.