Unraveling the role of high mobility group box protein 1 in severe trauma 英文参考文献.docVIP

Available online /content/13/6/1004 Commentary Unraveling the role of high mobility group box protein 1 in severe trauma Edward Abraham Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA Corresponding author: Edward Abraham, eabraham@ See related research by Cohen et al., /content/13/6/R174 Published: 12 November 2009 Critical Care 2009, 13:1004 (doi:10.1186/cc8141) This article is online at /content/13/6/1004 ? 2009 BioMed Central Ltd Abstract Initial studies suggested that HMGB1 acted as a pro- inflammatory mediator and was capable of contributing to organ system dysfunction and mortality in animal models of sepsis [5,6]. However, recent experiments using highly puri- fied HMGB1 have brought into question the ability of HMGB1 to activate cells and directly participate in acute inflam- matory conditions [7,8]. Rather, HMGB1 appears to poten- tiate inflammatory responses through avidly binding to pro- inflammatory mediators, including lipopolysaccharide, inter- leukin-1, and DNA [7,9]. The lack of endogenous inflam- matory activity of HMGB1 itself in cell culture experiments is consistent with the finding that high circulating levels of HMGB1 are present in patients who are clinically recovering from severe infection, such as pneumonia [10]. High mobility group box protein 1 (HMGB1) has been shown to participate in acute inflammatory reactions, including acute lung injury and sepsis. There is also evidence that circulating levels of HMGB1 are increased after severe trauma and are associated with clinically important outcome parameters, including mortality. Recent studies demonstrated that HMGB1 itself has little or no proinflam- matory activity, but is able to potentiate inflammatory responses through binding to mediators, such as endotoxin or cytokines. Important questions are to determine