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- Carmen Fiuza
- From the Critical Care Medicine Department, Warren G. Magnuson Clinical Center, National Institutes of Health, Bethesda; and Laboratory of Molecular Carcinogenesis, Division of Basic Sciences, National Cancer Institute, Bethesda, MD.
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- Michael Bustin
- From the Critical Care Medicine Department, Warren G. Magnuson Clinical Center, National Institutes of Health, Bethesda; and Laboratory of Molecular Carcinogenesis, Division of Basic Sciences, National Cancer Institute, Bethesda, MD.
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- Shefali Talwar
- From the Critical Care Medicine Department, Warren G. Magnuson Clinical Center, National Institutes of Health, Bethesda; and Laboratory of Molecular Carcinogenesis, Division of Basic Sciences, National Cancer Institute, Bethesda, MD.
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- Margaret Tropea
- From the Critical Care Medicine Department, Warren G. Magnuson Clinical Center, National Institutes of Health, Bethesda; and Laboratory of Molecular Carcinogenesis, Division of Basic Sciences, National Cancer Institute, Bethesda, MD.
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- Eric Gerstenberger
- From the Critical Care Medicine Department, Warren G. Magnuson Clinical Center, National Institutes of Health, Bethesda; and Laboratory of Molecular Carcinogenesis, Division of Basic Sciences, National Cancer Institute, Bethesda, MD.
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- James H. Shelhamer
- From the Critical Care Medicine Department, Warren G. Magnuson Clinical Center, National Institutes of Health, Bethesda; and Laboratory of Molecular Carcinogenesis, Division of Basic Sciences, National Cancer Institute, Bethesda, MD.
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- Anthony F. Suffredini
- From the Critical Care Medicine Department, Warren G. Magnuson Clinical Center, National Institutes of Health, Bethesda; and Laboratory of Molecular Carcinogenesis, Division of Basic Sciences, National Cancer Institute, Bethesda, MD.
抄録
<jats:p>Systemic inflammation because of sepsis results in endothelial cell activation and microvascular injury. High-mobility group protein-1 (HMGB1), a novel inflammatory molecule, is a late mediator of endotoxin shock and is present in the blood of septic patients. The receptor for advanced glycation end products (RAGE) is expressed on endothelium and is a receptor for HMGB1. Here we examine the effects of HMGB1 on human endothelial cell function. Recombinant human HMGB1 (rhHMGB1) was cloned and expressed in Escherichia coli and incubated with human microvascular endothelium. rhHMGB1 caused a dose- and time-dependent increase in the expression of intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), and RAGE. rhHMGB1 induced the secretion of tumor necrosis factor-α (TNFα), interleukin 8 (IL-8), monocyte chemotactic protein-1 (MCP-1), plasminogen activator inhibitor 1 (PAI-1), and tissue plasminogen activator (tPA) (P < .01). rhHMGB1 stimulation resulted in transient phosphorylation of mitogen-activated protein (MAP) kinases, extracellular signal-related kinase (ERK), Jun N-terminal kinase (JNK), and p38, and in nuclear translocation of transcription factors NF-κB and Sp1. These effects are partially mediated by TNFα autocrine stimulation, as anti-TNFα antibodies significantly decrease chemokine and adhesion molecule responses (P ≤ .002). Thus, rhHMGB1 elicits proinflammatory responses on endothelial cells and may contribute to alterations in endothelial cell function in human inflammation.</jats:p>
収録刊行物
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- Blood
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Blood 101 (7), 2652-2660, 2003-04-01
American Society of Hematology
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詳細情報 詳細情報について
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- CRID
- 1360292621144800640
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- NII論文ID
- 30022495431
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- ISSN
- 15280020
- 00064971
- http://id.crossref.org/issn/00064971
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- データソース種別
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- Crossref
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