Artemisinin protects mice against burn sepsis through inhibiting NLRP3 inflammasome activation

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• 作者：Huibao Long ; MD ^{longhuibao3hhsa@163.com" class="auth_mail" title="E-mail the corresponding author} ; Bincan Xu ; MM ^{xubincan42yae@yeah.net" class="auth_mail" title="E-mail the corresponding author} ; Yanling Luo ; MM ^{luoyanling45bs@163.com" class="auth_mail" title="E-mail the corresponding author} ; Keqin Luo ; MM ; ^{keqinluodoc@126.com" class="auth_mail" title="E-mail the corresponding author}
• 刊名：The American Journal of Emergency Medicine
• 出版年：2016
• 出版时间：May 2016
• 年：2016
• 卷：34
• 期：5
• 页码：772-777
• 全文大小：706 K

文摘

NLRP3 inflammasome activation is recently reported to be linked to the pathogenesis of sepsis. Artemisinin is shown to play beneficial effects in sepsis. However, the impacts of artemisinin on burn sepsis have not been investigated. This study is designed to investigate the role of artemisinin in burn sepsis and the involvement of NLRP3 inflammasome activation.

Methods

Male BALB/c mice were randomly divided into sham burn, burn, burn sepsis, and artemisinin treated groups. Inflammatory cytokines were measured by enzyme-linked immunosorbent assay. Adhesion molecules and neutrophil infiltration in lung and heart were detected by real-time polymerase chain reaction. Mortality rates were monitored. Artemisinin was added to Raw 264.7 cells that were stimulated with burn sepsis serum in the presence/absence of an inhibitor of NLRP3 inflammasome, 3, 4-methylenedioxy-β-nitrostyrene. Interleukin (IL) 1β and IL-18 messenger RNA expression as well as NLRP3 and caspase 1 protein were measured.

Results

Production of inflammatory cytokines in serum, levels of adhesion molecules and neutrophil infiltration in lung and heart, and mortality rate of burn septic mice were significantly higher than those of control. These effects were attenuated by artemisinin. Artemisinin down-regulated protein levels of NLRP3 and caspase 1 and inhibited the increases of IL-1β and IL-18 messenger RNA expression from Raw 264.7 cells that were stimulated with burn sepsis serum. These effects of artemisinin were not further strengthened in the presence of 4-methylenedioxy-β-nitrostyrene.

Conclusion

Artemisinin protects mice from burn sepsis by attenuating the inflammatory response and alleviating inflammatory infiltration in vital organs, likely through inhibiting the activation of NLRP3 inflammasome.