Mitochondrial DNA plays an important role in lung injury induced by sepsis
- 5 December 2018
- journal article
- research article
- Published by Wiley in Journal of Cellular Biochemistry
- Vol. 120 (5), 8547-8560
- https://doi.org/10.1002/jcb.28142
Abstract
The effects and mechanisms of mitochondrial DNA (mtDNA) in the development of sepsis‐induced lung injury is not well understood. In our present study, we studied the mtDNA effects in sepsis‐induced lung injury model, in vitro and in vivo. Compared with the Normal group, the lung histopathological score, the number of positive apoptosis cell, wet/dry (W/D) ratio and TNF‐α, IL‐1β, and IL‐6 concentrations of lipopolysaccharides (LPSs) and mtDNA groups were significantly increased (P < 0.001, respectively). Meanwhile, the lung histopathological score, positive W/D ratio, number of apoptosis cell and tumor necrosis factor‐α (TNF‐α), interleukin (IL)‐1β, and IL‐6 concentrations of LPS + mtDNA and small interfering RNA (siRNA)‐NC + LPS + mtDNA groups were significantly upregulated compared with those of LPS group (P < 0.05, respectively). However, the lung histopathological score, the number of positive apoptosis cell, W/D ratio and TNF‐α, IL‐1β, and IL‐6 concentrations were significantly improved within the toll‐like receptor (TLR9)siRNA + LPS + mtDNA group compared with the LPS group (P < 0.01, respectively). The TLR9, MyD88, and NF‐κB proteins or gene expressions of the LPS group and mtDNA group were significantly upregulated compared with those of Normal group by Western blot analysis or immunohistochemistry assay (P < 0.01, respectively), and the TLR9, MyD88, and NF‐κB proteins or gene expressions of LPS + mtDNA and siRNA‐NC + LPS + mtDNA groups were significantly enhanced compared with those of LPS group (P < 0.05, respectively). However, the TLR9, MyD88, and NF‐κB proteins or gene expressions of TLR9siRNA + LPS + mtDNA group were significantly suppressed compared with those of the LPS group (P < 0.01, respectively). In conclusion, mtDNA could provoke lung injury induced by sepsis via regulation of TLR9/MyD88/NF‐κB pathway in vitro and in vivo.Keywords
Funding Information
- National Natural Science Foundation of China (81460015)
This publication has 26 references indexed in Scilit:
- Mitochondrial DAMPs Increase Endothelial Permeability through Neutrophil Dependent and Independent PathwaysPLOS ONE, 2013
- Plasma nuclear and mitochondrial DNA levels as predictors of outcome in severe sepsis patients in the emergency roomJournal of Translational Medicine, 2012
- Nuclease-resistant immunostimulatory phosphodiester CpG oligodeoxynucleotides as human Toll-like receptor 9 agonistsBMC Biotechnology, 2011
- Mitochondrial Damage Associated Molecular Patterns From Femoral Reamings Activate Neutrophils Through Formyl Peptide Receptors and P44/42 MAP KinaseJournal of Orthopaedic Trauma, 2010
- CpG oligonucleotides induce an immune response of odontoblasts through the TLR9, MyD88 and NF-κB pathwaysBiochemical and Biophysical Research Communications, 2010
- The role of pattern-recognition receptors in innate immunity: update on Toll-like receptorsNature Immunology, 2010
- Pattern Recognition Receptors and InflammationCell, 2010
- Circulating mitochondrial DAMPs cause inflammatory responses to injuryNature, 2010
- Mechanical ventilation using non-injurious ventilation settings causes lung injury in the absence of pre-existing lung injury in healthy miceCritical Care, 2009
- Sepsis: definition, epidemiology, and diagnosisBMJ, 2007