The role of TREM-1/NF-κB pathway in regulation of metformin on mouse acute lung injury
Objective This study was designed to examine the effect of metformin on triggering receptors expressed on myeloid cells-1(TREM-1)in a lipopolysaccharide(LPS)induced acute lung injury(ALI)mouse model and explore whether metformin uti-lizes TREM-1/NF-κB pathway to reduce ALI in mice.Methods First of all,an ALI mouse model was established by intraperito-neal injection of 10 mg/kg LPS,and intervention with metformin or TREM-1 receptor antagonist was used to examine the effect of metformin on TREM-1 expression in ALI mice.Total protein level,total cell and neutrophil count,lactate dehydrogenase(LDH)and myeloperoxidase(MPO)were determined in the lavage fluid(BALF),and the wet/dry specific gravity of lung tissues were as-sessed.NF-κB and TREM-1 mRNA expression was assessed through Real time-PCR,while NF-κB,IL-18,IL-1β,TNF-α and TREM-1 protein expression levels were measured by Western blots.Results Our results showed that metformin reduced the ex-pression of TREM-1 in the lung tissue of ALI mice.After antagonizing TREM-1,metformin could alleviate pathological damage,protein exudation,and neutrophil infiltration in lung tissue,and expression of NF-κB,IL-18,IL-1β,TNF-α was inhibited.Con-clusion Metformin can reduce the expression of inflammatory factors,vascular permeability,and infiltration of inflammatory cells,thereby alleviating LPS-induced ALI,and its mechanism may be related to TREM-1/NF-κ B pathway.
acute lung injurymetformintriggering receptors expressed on myeloid cells-1(TREM-1)nuclear factor-κB
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