Reactive oxygen species and cell injury

Burn injury is a complex traumatic event with various local and systemic effects. The systemic pathophysiologic changes following thermal injuries affect multiple organs and body systems leading to clinical manifestations including shock, intestinal alterations, respiratory and renal failure, immunosuppression and others. One of the molecules activated after severe injuries is the Inflammasome NLRP3. For these experiments we used 3 different strain of mice: Nlrp3 k-in mice and ko mice and the wild type strain C57BL/6J. Molecular (p-JNK, p-p38, p-ASK1, and BAX) and hystoligical evaluations have been conducted on kidneys samples providing evidence of a role of the NLRP3 inflammasome in systemic inflammatory response following thermal injury. Indeed, under this peculiar condition KO-animals displayed an high mortality rate (over 60%) during the first 4 days, and none of the KO mice survived after day 7. On the other hand the animals overexpressing the NLRP3 survived as the WT ones. The excessive triggering of the apoptotic/inflammatory pathways in KI-animals was evident even under normal conditions, in fact pyroptosis was detected in kidneys from sham animals. KO-mice showed an increased activation of apoptosis-related molecules after 7 days, while in KI animals the inflammatory pathway was more activated compared to either WT and KO mice. These results suggest that the NLRP3 inflammasome is of fundamental importance in survival and recovery from systemic injury.