Protective effect of IL-35 mRNA deliveried by lipid nanoparticles against lipopolysaccharide induced acute lung injury in mice
10.3867/j.issn.1000-3002.2024.11.003
- VernacularTitle:脂质纳米粒递送IL-35 mRNA对脂多糖诱导小鼠急性肺损伤的保护作用
- Author:
Jierui MAI
1
;
Huisheng SUN
;
Yuqin LIAO
;
Yanyan LI
;
Shumei WANG
;
Jing YANG
;
Shengqi WANG
Author Information
1. 广东药科大学,广东 广州 510006
- Keywords:
IL-35;
mRNA;
lipid nanoparticles;
lipopolysaccharide;
acute lung injury;
inflammation
- From:
Chinese Journal of Pharmacology and Toxicology
2024;38(11):826-833
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE To investigate the protective effect of interleukin-35(IL-35)mRNA-lipid nanoparticles(LNP)against lipopolysaccharide(LPS)-induced acute lung injury(ALI)in mice.METHODS Fifity-six mice were randomly divided into 7 groups with 8 mice in each,including the normal control group,IL-35 mRNA-LNP(250 μg·kg-1)group,LPS group,LPS+IL-35 mRNA-LNP(50,125 and 250 μg·kg-1)group and LPS+Dexamethasone(DXM)group.Except for the normal control group and IL-35 mRNA-LNP(250 μg·kg-1)group and ALI model was established by tracheal infusion of LPS in each of the other groups.IL-35 mRNA-LNP(250 μg·kg-1)group and LPS+IL-35 mRNA-LNP(50,125 and 250 μg·kg-1)group were injected with a corresponding dose of LNP encapsulated mRNA complex via the tail vein while the LPS+DXM group was injected with DXM via the tail vein.Lung coefficient and the wet to dry weight ratio(W/D)of lung tissue were recorded.The mRNA levels of inflammatory cytokines tumor necrosis factor-α(TNF-α),Interleukin-6(IL-6)and IL-1βof lung homogenates were detected by real-time fluorescence quantitative PCR(RT-qPCR).LDH activity of lung homogenates and the protein levels of IL-35,TNF-α,IL-6 and IL-1β in lung homogenate were detected by corresponding kits.Hematoxylin-eosin(HE)staining was used to observe and analyze the pathological injury to lung tissue.The expres-sion of Lymphocyte antigen 6G(Ly6G)was detected by Immunofluorescence to reflect the infiltration of neutrophils.RESULTS Compared with the normal control group,LPS group and LPS+DXM group,IL-35 protein expression levels in lung homogenates of the other groups were more significant(P<0.01).Compared with the normal control group,lung coefficient,W/D ratio of lung tissue,LDH activity,mRNA levels and the protein levels of TNF-α,IL-6 and IL-1β in lung homogenates were significantly increased in the LPS group(P<0.01),accompanied by alveolar hemorrhage,alveolar wall thickening and neutro-phils infiltration.After IL-35 mRNA-LNP administration,lung coefficient,W/D ratio of lung tissue,LDH activity,mRNA levels and the protein levels of TNF-α,IL-6 and IL-1β in lung homogenates were signifi-cantly decreased(P<0.01),and alveolar hemorrhage,alveolar wall thickening and neutrophil infiltration were obviously improved.CONCLUSION IL-35 mRNA-LNP can express IL-35 protein in lung tissue of mice,and effectively improve LPS-induced ALI in mice by inhibiting the expression of proinflammatory factors.
