Acute Amelioration of Inflammatory Activity Caused by Endothelin-2 Deficiency during Acute Lung Injury

In this study, we performed 24 hours intratracheal lipopolysaccharide (LPS) instillation or PBS control as an in vivo ALI model in eight-week-old conditional Edn2 knockout mice (Edn2-iKO), with Edn2-floxed mice as controls. Bronchoalveolar lavage (BAL) fluid and tissue were collected after exsanguination and analyzed for its cellular, molecular, functional, and histological inflammatory phenotypes. We found that Edn2-iKO mice displayed a reduced pro-neutrophilic inflammatory phenotype even after acute LPS treatment, shown by the reduction in the overall protein concentration and neutrophil count in bronchoalveolar lavage fluids. Further investigation revealed a reduction in mRNA interferon gamma (IFNγ) level of Edn2-iKO lungs and suppression of its downstream signaling, including phosphorylated level of STAT1 and IL-1β secretion, leading to reduced NFĸB activation. To conclude, Edn2 deletion suppressed acute lung inflammation by reducing neutrophil-mediated IFNγ/STAT1/IL-1β/NFĸB signaling cascade. Targeting Edn2 signaling may be beneficial for the development of novel treatment options for ALI.PMID:37941117 | DOI:10.24546/0100483406
Source: Kobe J Med Sci - Category: General Medicine Authors: Source Type: research