Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036690 (sepsis)
 59,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

High mobility group box-1 protein (HMGB1, formerly known as HMG-1), a highly conserved ubiquitous protein, has been for a long time described as a nuclear DNA-binding protein involved in nucleosome stabilization and gene transcription. Recent discoveries indicate that HMGB1 is released from activated innate immune cells or necrotic cells and functions as an important mediator of endotoxemia, sepsis, arthritis, and local inflammation. Therapeutic agents that inhibit HMGB1 release or action confer significant protection against endotoxemia, sepsis, and arthritis in animal models and thus hold potential for the clinical management of various inflammatory diseases.
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PMID:Extracellular HMGB1 as a proinflammatory cytokine. 1521 6

High Mobility Group Box chromosomal protein 1 (HMGB1) is a nuclear DNA-binding protein acting as a proinflammatory cytokine when released in the extracellular space from necrotic cells,activated macrophages and dendritic cells. HMGB1 acts on a specific receptor, RAGE (receptor for advanced glycation end-products), and induces prolonged inflammation, organ failure, septicaemia and death. The aim of the study was to determine the diagnostic value of plasma HMGB1 concentration and its role in the development of organ failure in patients with disseminated intravascular coagulation (DIC). Plasma HMGB-1 levels were measured in patients with suspected DIC and their relationships with DIC, organ failure and clinical outcome were determined. The study took place at the intensive care facility, Mie University School of Medicine and comprised 201 patients with suspected DIC. Plasma HMGB1 was below the detection limit in normal subjects, but moderately elevated in patients with infectious diseases (4.54 +/- 8.18 ng/ml, mean +/- SD), malignancies (2.15 +/- 5.34 ng/ml),and traumas (6.47 +/- 13.13 ng/ml). DIC was associated with significantly high plasma HMGB1 (14.05 +/- 12.56 ng/ml) in these patients. The highest HMGB1 levels were in patients with organ failure (8.29 +/- 10.99 ng/ml) and non-survivors (16.58 +/- 11.01 ng/ml). HMGB1 plasma levels correlated with the DIC score and sepsis-related organ failure assessment (SOFA) score. In conclusion, our data suggest that HMGB-1 is a potentially suitable prognostic marker of OF or DIC.
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PMID:Plasma concentrations and importance of High Mobility Group Box protein in the prognosis of organ failure in patients with disseminated intravascular coagulation. 1636 39

High-mobility group box-1 (HMGB1) protein was originally described as a nuclear DNA-binding protein that functions as a structural cofactor critical for proper transcriptional regulation and gene expression. Recent studies indicate that damaged, necrotic cells liberate HMGB1 into the extracellular milieu where it functions as a proinflammatory cytokine. Indeed, HMGB1 represents a novel family of inflammatory cytokines composed of intracellular proteins that can be recognized by the innate immune system as a signal of tissue damage. Posttranslational modifications of HMGB 1 determine its interactions with other proteins and modulate its biological activity. However, very little is known about how these posttranslational modifications of HMGB1 affect its extracellular inflammatory activity and pathological potential. These studies can provide more efficient therapeutic strategies directed against specific HMGB1 isoforms. Therapeutic strategies against these specific HMGB1 isoforms can serve as models for more efficient therapeutic strategies against rheumatoid arthritis or sepsis. This article reviews the recent studies on HMGB1 regulation and their impact on the inflammatory activity and pathological contribution of HMGB 1 to infectious and inflammatory disorders.
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PMID:High-mobility group box-1 isoforms as potential therapeutic targets in sepsis. 1717 10

High mobility group box-1 protein (HMGB1), a highly conserved nuclear DNA-binding protein, is involved in maintenance of nucleosome structure and regulation of gene replication, transcription and translation. Recently, there is accumulating evidence that HMGB1 can be passively or actively released from the nucleus to the extracellular milieu and act as a late proinflammatory cytokine that mediates development of inflammatory diseases, including sepsis. In addition, HMGB1 can also act as an "alarm signal" regulating immune response of host. In this article, we summarized the structure, secretion and receptor signaling pathways of HMGB1. Furthermore, the role and potential mechanism underlying HMGB1 in regulation of immune function were also discussed.
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PMID:[The extracellular role of high mobility group box-1 protein in regulation of immune response]. 2193 16