title: Artemisinin protects mice against burn sepsis through inhibiting NLRP3 inflammasome activation.
abstract: BACKGROUND
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Emergency, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, China. Electronic address: longhuibao3hhsa@163.com.
authors.forename: Huibao
authors.initials: H
authors.lastname: Long
authors.affiliation: Department of Emergency, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, China. Electronic address: xubincan42yae@yeah.net.
authors.forename: Bincan
authors.initials: B
authors.lastname: Xu
authors.affiliation: Department of Emergency, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, China. Electronic address: luoyanling45bs@163.com.
authors.forename: Yanling
authors.initials: Y
authors.lastname: Luo
authors.affiliation: Department of Emergency, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, China. Electronic address: keqinluodoc@126.com.
authors.forename: Keqin
authors.initials: K
authors.lastname: Luo
mesh_terms: D000818:Animals; D000890:Anti-Infective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D037621:Artemisinins / Q000494:pharmacology / Q000627:therapeutic use*; D015415:Biomarkers / Q000378:metabolism; D002056:Burns / Q000150:complications*; D002352:Carrier Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D058847:Inflammasomes / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D000067996:RAW 264.7 Cells; D011897:Random Allocation; D060888:Real-Time Polymerase Chain Reaction; D018805:Sepsis / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*
chemical_list: D000890:Anti-Infective Agents; D037621:Artemisinins; D015415:Biomarkers; D002352:Carrier Proteins; D016207:Cytokines; D058847:Inflammasomes; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C492716:Nlrp3 protein, mouse; C031327:artemisinin