First Author | Ding Z | Year | 2014 |
Journal | Biochem Biophys Res Commun | Volume | 451 |
Issue | 4 | Pages | 637-43 |
PubMed ID | 25130466 | Mgi Jnum | J:220107 |
Mgi Id | MGI:5632244 | Doi | 10.1016/j.bbrc.2014.08.034 |
Citation | Ding Z, et al. (2014) LOX-1 - dependent mitochondrial DNA damage and NLRP3 activation during systemic inflammation in mice. Biochem Biophys Res Commun 451(4):637-43 |
abstractText | BACKGROUND: Lectin-like oxidized low-density lipoprotein scavenger receptor-1 (LOX-1) is known to be involved in many pathophysiological events, such as inflammation. METHODS: To 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. RESULTS: We 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-1beta and IL-18. These mice also had much less mtDNA damage and only limited NLRP3 inflammasome expression. CONCLUSIONS: These in vivo observations indicate that LOX-1 plays a key role in mtDNA damage which then leads to NLRP3 inflammasome activation during inflammation. |