Mitochondrial DNA-induced inflammatory responses and lung injury in thermal injury murine model: Protective effect of cyclosporine-A

Abstract

Burn trauma is generally associated with profound inflammation and organ injuries, especially the lung. Damage-associated molecular patterns (DAMPs), such as mitochondrial DNA (mtDNA), released after tissue injuries, play a crucial role in the development of the inflammation. The aim of our study was to investigate the protective profiles of cyclosporine-A (CsA) in murine models with thermal injury. We studied 24 C57BL/6 mice which were randomly subjected to four groups: a sham-operation group (SO group, n = 6), an experiment group (a full-thickness thermal injury covered 30% of the TBSA, n = 6), a low-CsA group (injection of 2.5 mg/kg of CsA 15 min before the thermal injury, n = 6) and a high-CsA group (injection of 25 mg/kg of CsA 15 min before the thermal injury, n = 6). Systemic inflammatory mediators and plasma mtDNA were measured while lung injury was evaluated pathologically and cytosolic cytochrome c and mtDNA were detected. Noticeable increases in concentration of mtDNA and inflammatory mediators were obtained in the experiment group and two CsA groups comparing with the SO group (P < .05). There were significant decreases in the concentrations of mtDNA and inflammatory mediators with increasing doses of CsA (P < .05). Similarly, severity of lung injury was mitigated with increasing doses of CsA. Meanwhile, CsA also attenuated oxidative stress and release of cytochrome c and mtDNA in the lung tissue on a dose-dependent manner (P < .05). Our results suggested mtDNA contributes to the development of thermal injury-induced inflammation and lung injury. CsA might exert dual protective effects, reducing the release of mtDNA and limiting the mtDNA-induced mitochondrial dysfunction in the lung, on the thermal injury-induced acute lung injury.