LOX-1 – dependent mitochondrial DNA damage and NLRP3 activation during systemic inflammation in mice

Abstract

BackgroundLectin-like oxidized low-density lipoprotein scavenger receptor-1 (LOX-1) is known to be involved in many pathophysiological events, such as inflammation. MethodsTo clarify the role of LOX-1 in mtDNA damage and NLRP3 inflammasome activation, we studied wild-type (WT) and LOX-1 knockout (KO) mice given thioglycollate, an inflammatory stimulus. ResultsWe observed intense inflammatory response (CD45 and CD68 expression) and mtDNA damage in spleen and kidneys of WT mice given thioglycollate. The abrogation of LOX-1 (use of LOX-1 knockout mice) reduced the inflammatory response as well as mtDNA damage (P<0.05 vs. WT mice). We also observed that mice with LOX-1 deletion had markedly reduced expression of caspase-1 (P10 and P20 subunits) as well as cleaved IL-1β and IL-18. These mice also had much less mtDNA damage and only limited NLRP3 inflammasome expression. ConclusionsThese in vivo observations indicate that LOX-1 plays a key role in mtDNA damage which then leads to NLRP3 inflammasome activation during inflammation.