Emergency Department, First Hospital of China Medical University, Shenyang City, 110001, Liaoning Province, China.
Respir Physiol Neurobiol. 2021 Oct;292:103711. doi: 10.1016/j.resp.2021.103711. Epub 2021 Jun 6.
Exosome is a novel tool with an essential role in cell communication. However, its role in the pathogenesis of sepsis-induced acute lung injury is currently unknown. Here, we first found that lipopolysaccharide (LPS) could up-regulate the expression of pro-inflammatory cytokines and promote exosomes release in the murine alveolar macrophage cell line (MHs cells). Moreover, we found MHs cells derived exosomes also maintain the pro-inflammatory effect after LPS stimulation. Treating with hydrochloride hydrate (GW4869) could dose-dependently downregulated the release of exosomes and inhibited the upregulation of inflammatory cytokines in MHs cells with LPS treatment. Also, we further identified GW4869 administration induced the remission of histopathologic changes, the reduction of pro-inflammatory cytokines in lung tissue, and inhibit serum exosomes release. These results indicate that the downregulation of exosome release by GW4869 might protect lung tissue from LPS induced injury through the suppression of excessive inflammatory responses, suggesting its potential therapeutic effects on sepsis-induced acute lung injury.
外泌体是一种新型的细胞通讯工具，在细胞通讯中具有重要作用。然而，其在脓毒症诱导的急性肺损伤发病机制中的作用尚不清楚。在这里，我们首先发现脂多糖（LPS）可以上调促炎细胞因子的表达，并促进小鼠肺泡巨噬细胞系（MHs 细胞）中释放外泌体。此外，我们发现 LPS 刺激后的 MHs 细胞衍生的外泌体也保持促炎作用。盐酸盐（GW4869）处理可剂量依赖性地下调 LPS 处理的 MHs 细胞中外泌体的释放，并抑制促炎细胞因子的上调。此外，我们进一步确定 GW4869 给药诱导组织病理学变化的缓解、肺组织中促炎细胞因子的减少以及抑制血清外泌体的释放。这些结果表明，GW4869 通过抑制过度的炎症反应来下调外泌体的释放，可能对 LPS 诱导的损伤起到保护作用，提示其对脓毒症诱导的急性肺损伤具有潜在的治疗作用。
