title: LOX-1 - dependent mitochondrial DNA damage and NLRP3 activation during systemic inflammation in mice.
abstract: 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-1β 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.
authors.affiliation: Central Arkansas Veterans Healthcare System and the Department of Medicine, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA; Key Laboratory for Biomechanics and Mechanobiology of Ministry of Education, School of Biological Science and Medical Engineering, Beihang University, Beijing 100191, PR China.
authors.forename: Zufeng
authors.initials: Z
authors.lastname: Ding
authors.affiliation: Central Arkansas Veterans Healthcare System and the Department of Medicine, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA. Electronic address: SLiu2@uams.edu.
authors.forename: Shijie
authors.initials: S
authors.lastname: Liu
authors.affiliation: Central Arkansas Veterans Healthcare System and the Department of Medicine, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
authors.forename: Xianwei
authors.initials: X
authors.lastname: Wang
authors.affiliation: Central Arkansas Veterans Healthcare System and the Department of Medicine, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
authors.forename: Sue
authors.initials: S
authors.lastname: Theus
authors.affiliation: Key Laboratory for Biomechanics and Mechanobiology of Ministry of Education, School of Biological Science and Medical Engineering, Beihang University, Beijing 100191, PR China.
authors.forename: Yubo
authors.initials: Y
authors.lastname: Fan
authors.affiliation: Key Laboratory for Biomechanics and Mechanobiology of Ministry of Education, School of Biological Science and Medical Engineering, Beihang University, Beijing 100191, PR China.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Deng
authors.affiliation: Central Arkansas Veterans Healthcare System and the Department of Medicine, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA. Electronic address: MehtaJL@UAMS.edu.
authors.forename: Jawahar L
authors.initials: JL
authors.lastname: Mehta
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D020170:Caspase 1 / Q000096:biosynthesis; D004249:DNA Damage / Q000187:drug effects*; D004272:DNA, Mitochondrial / Q000378:metabolism*; D058847:Inflammasomes / Q000378:metabolism*; D007249:Inflammation / Q000139:chemically induced*; D020382:Interleukin-18 / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D051127:Scavenger Receptors, Class E / Q000235:genetics / Q000502:physiology*; D013864:Thioglycolates
chemical_list: D002352:Carrier Proteins; D004272:DNA, Mitochondrial; D058847:Inflammasomes; D020382:Interleukin-18; D053583:Interleukin-1beta; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C492716:Nlrp3 protein, mouse; D051127:Scavenger Receptors, Class E; D013864:Thioglycolates; D020170:Caspase 1
keywords: LOX-1; Mitochondrial DNA damage; NLRP3 inflammasome