生物
细胞生物学
炎症体
分泌物
细胞外
炎症
微泡
串扰
肝细胞
细胞内
巨噬细胞
微泡
信号转导衔接蛋白
免疫学
信号转导
生物化学
小RNA
基因
体外
物理
光学
作者
Priyanka Ghosh,Kyo Sasaki,Isabel Aranzazu Pulido Ruiz,Kayla E. King,Steven A. Weinman,Ann L. Wozniak
摘要
Macrophage-derived extracellular vesicles (EVs) play key roles in intercellular communication. Within the liver, they have been linked to several inflammatory diseases including nonalcoholic fatty liver disease (NAFLD). In this study, we found that inflammatory macrophages cause injury to hepatocytes, in part by a cell-cell crosstalk phenomenon involving the secretion of EVs containing pro-inflammatory cargo. Incorporation of these inflammatory signals into EV requires the cleavage of the trafficking adaptor protein RILP, which, as previously shown, results from inflammasome-mediated caspase-1 activation. RILP cleavage can be blocked by overexpressing a dominant negative, non-cleavable form of RILP (ncRILP). EV preparations from ncRILP-expressing cells are, by themselves, sufficient to suppress inflammatory effects in hepatocytes. These results suggest that both direct RILP manipulation and/or supplying ncRILP-modified EVs could be used as a novel therapy for the treatment of inflammatory liver diseases.
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