RNY (YRNA)-derived small RNAs regulate cell death and inflammation in monocytes/macrophages.

摘要: The recent discovery of new classes small RNAs has opened unknown territories to explore regulations physiopathological events. We have recently demonstrated that RNY (or Y RNA)-derived (referred as s-RNYs) are an independent class clinical biomarkers detect coronary artery lesions and associated with atherosclerosis burden. Here, we studied the role s-RNYs in human mouse monocytes/macrophages shown lipid-laden s-RNY expression is timely correlated activation both NF-κB caspase 3-dependent cell death pathways. Loss- or gain-of-function experiments activate 3 signaling pathways ultimately promoting inflammatory responses. As, atherosclerosis, Ro60-associated generated by apoptotic macrophages released blood patients, investigated extracellular function s-RNY/Ro60 complex. Our data complex induces NF-κB-dependent inflammation, when added medium cultured monocytes/macrophages. Finally, mediated Toll-like receptor 7 (TLR7). Indeed using chloroquine, which disrupts endosome-localized TLRs 3, 7, 8 9 more specific TLR7/9 antagonist, phosphorothioated oligonucleotide IRS954, blocked effect either intracellular s-RNYs. These results position relevant novel functional molecules impacts on macrophage physiopathology, indicating their potential mediators diseases, such atherosclerosis.