脓毒症诱导的急性肺损伤与肺上皮细胞损伤有关。这项研究分析了抗菌肽LL37与线粒体DNA(LL37-mtDNA)的作用及其在脂多糖(LPS)处理的大鼠II型肺泡上皮细胞(RLE-6TN细胞)中的潜在作用机制。用LPS单独或LL37-mtDNA处理RLE-6TN细胞,其次是转录组测序。使用生物信息学工具筛选差异表达和关键基因。LL37-mtDNA对细胞活力的影响,炎症,凋亡,活性氧(ROS)的产生,在LPS处理的RLE-6TN细胞中评估自噬相关标志的表达。此外,在体外研究了LL37-mtDNA处理后Hsp90aa1沉默的作用。LL37-mtDNA进一步抑制细胞活力,细胞凋亡增强,促进炎症细胞因子的释放,增加ROS产量,和在LPS处理的RLE-6TN细胞中LC3B表达升高。使用转录组测序和生物信息学,确定了十个候选基因,其中3个核心基因在LPS+LL37-mtDNA组中被证实上调。此外,Hsp90aa1下调减弱了LL37-mtDNA对LPS处理的RLE-6TN细胞的影响。Hsp90aa1沉默可能是抵消LL37-mtDNA对生存力影响的关键目标,凋亡,炎症,LPS处理的RLE-6TN细胞中的自噬激活。
Sepsis-induced acute lung injury is associated with lung epithelial cell injury. This study analyzed the role of the antimicrobial peptide LL37 with mitochondrial DNA (LL37-
mtDNA) and its potential mechanism of action in lipopolysaccharide (LPS)-treated rat type II alveolar epithelial cells (RLE-6TN cells). RLE-6TN cells were treated with LPS alone or with LL37-
mtDNA, followed by transcriptome sequencing. Differentially expressed and pivotal genes were screened using bioinformatics tools. The effects of LL37-mtDNA on cell viability, inflammation, apoptosis, reactive oxygen species (ROS) production, and autophagy-related hallmark expression were evaluated in LPS-treated RLE-6TN cells. Additionally, the effects of Hsp90aa1 silencing following LL37-
mtDNA treatment were investigated in vitro. LL37-
mtDNA further suppressed cell viability, augmented apoptosis, promoted the release of inflammatory cytokines, increased ROS production, and elevated LC3B expression in LPS-treated RLE-6TN cells. Using transcriptome sequencing and bioinformatics, ten candidate genes were identified, of which three core genes were verified to be upregulated in the LPS + LL37-mtDNA group. Additionally, Hsp90aa1 downregulation attenuated the effects of LL37-
mtDNA on LPS-treated RLE-6TN cells. Hsp90aa1 silencing possibly acted as a crucial target to counteract the effects of LL37-mtDNA on viability, apoptosis, inflammation, and autophagy activation in LPS-treated RLE-6TN cells.