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Detection of Inflammasome Activation and Pyroptotic Cell Death in Murine Bone Marrow-derived Macrophages
Published on: May 21, 2018
LOX-1 - dependent mitochondrial DNA damage and NLRP3 activation during systemic inflammation in mice
Zufeng Ding1, Shijie Liu2, Xianwei Wang2
1Central 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.
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.
