Báo cáo y học: Bench-to-bedside review: High-mobility group box 1 and critical illnes

Tuyển tập các báo cáo nghiên cứu về y học được đăng trên tạp chí y học Critical Care giúp cho các bạn có thêm kiến thức về ngành y học đề tài: Bench-to-bedside review: High-mobility group box 1 and critical illness...
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Báo cáo y học: " Bench-to-bedside review: High-mobility group box 1 and critical illnes" Available online http://ccforum.com/content/11/5/229ReviewBench-to-bedside review: High-mobility group box 1 and criticalillnessMitchell P FinkDepartments of Critical Care Medicine, Surgery and Pharmacology, University of Pittsburgh, 3550 Terrace Street, Pittsburgh, PA 15261, USACorresponding author: Mitchell P Fink, fink.mp@logicaltherapeutics.comPublished: 19 September 2007 Critical Care 2007, 11:229 (doi:10.1186/cc6088)This article is online at http://ccforum.com/content/11/5/229© 2007 BioMed Central LtdAbstract HMG1 box contains a string of 70 to 80 amino acid residues, which is folded into a characteristic, twisted, L-shapedHigh-mobility group box 1 (HMGB1) is a DNA-binding protein that structure [5,7]. HMGB1 facilitates the binding of severalalso exhibits proinflammatory cytokine-like activity. HMGB1 is regulatory protein complexes to DNA, particularly members ofpassively released by necrotic cells and also is actively secreted byimmunostimulated macrophages, dendritic cells, and enterocytes. the nuclear hormone-receptor family [8,9], V(D)J recombi-Although circulating HMGB1 levels are increased relative to nases [10], and the tumor suppressor proteins, p53 and p73healthy controls in patients with infections and severe sepsis, [11].plasma or serum HMGB1 concentrations do not discriminate reliablybetween infected and uninfected critically ill patients. Nevertheless, The cytokine-like role of high-mobility group box 1administration of drugs that block HMGB1 secretion or of anti- In 1999, Wang and colleagues [12] identified HMGB1 as aHMGB1 neutralizing antibodies has been shown to ameliorateorgan dysfunction and/or improve survival in numerous animal cytokine-like mediator of lipopolysaccharide (LPS)-inducedmodels of critical illness. Because HMGB1 tends to be released mortality in mice. Subsequently, these findings were extendedrelatively late in the inflammatory response (at least in animal by Yang and colleagues [13], who showed that HMGB1 ismodels of endotoxemia or sepsis), this protein is an attractive also a mediator of lethality in mice rendered septic by thetarget for the development of new therapeutic agents for the induction of polymicrobial bacterial peritonitis. Additionaltreatment of patients with various forms of critical illness. studies documented that extracellular HMGB1 can promoteIntroduction tumor necrosis factor (TNF) release from mononuclear cellsOriginally identified in the early 1960s [1], high-mobility group [14] and increase the permeability of Caco-2 monolayers [15].(HMG) proteins have been isolated and characterized from awide variety of eukaryotic species, ranging from yeast to One of the most interesting features of HMGB1 as ahumans [2]. Based on the presence of characteristic cytokine-like mediator of inflammation is that this protein isfunctional sequences, three HMG subgroups have been released much later in the inflammatory process than are theidentified [3-5]: the HMGB family, the HMGN family, and the classical ‘alarm-phase’ cytokines, such as TNF and interleukin (IL)-1β. For example, in mice, injection of a bolus dose of LPSHMGA family. All HMG proteins bind DNA and are soluble in5% perchloric acid [2]. HMG proteins all have an unusual elicits a monophasic spike in circulating TNF which peaksamino acid composition characterized by a high content of within 60 to 90 minutes of the proinflammatory challenge and is over within 4 hours [16]. The peak in IL-1β concentrationcharged amino ac ...