| B7-H3 augments the inflammatory response and is associated with human sepsis. | |
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MedLine Citation:
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PMID: 20696859 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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B7-H3, a new member of the B7 superfamily, acts as both a T cell costimulator and coinhibitor, and thus plays a key role in the regulation of T cell-mediated immune responses. However, it is unclear whether B7-H3 is involved in the innate immune monocyte/macrophage-mediated inflammatory response. In this paper, we show that, although B7-H3 alone failed to stimulate proinflammatory cytokine release from murine macrophages, it strongly augmented both LPS- and bacterial lipoprotein-induced NF-kappaB activation and inflammatory response. This occurred in both a TLR4- and TLR2-dependent manner. Blockage of B7-H3 in vivo attenuated LPS-induced proinflammatory cytokine release and endotoxic shock-related lethality. Furthermore, we found that patients diagnosed with sepsis, in contrast to healthy individuals, exhibited significant levels of raised plasma soluble B7-H3 (sB7-H3) and that this level correlated with the clinical outcome and levels of plasma TNF-alpha and IL-6. In addition, a putative receptor for B7-H3 was detected on monocytes and peritoneal macrophages from septic patients but not on monocytes from healthy donors. Stimulation of human monocytes with LPS and inflammatory cytokines led to a substantial release of sB7-H3. Taken together, our data indicate that significantly elevated plasma sB7-H3 in septic patients may predict a poor outcome. Furthermore, we demonstrate that B7-H3 functions as a costimulator of innate immunity by augmenting proinflammatory cytokine release from bacterial cell wall product-stimulated monocytes/macrophages and may contribute positively to the development of sepsis. |
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Authors:
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Guangbo Zhang; Jian Wang; Justin Kelly; Guohao Gu; Jianquan Hou; Yinghui Zhou; H Paul Redmond; Jiang Huai Wang; Xueguang Zhang |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-08-09 |
Journal Detail:
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Title: Journal of immunology (Baltimore, Md. : 1950) Volume: 185 ISSN: 1550-6606 ISO Abbreviation: J. Immunol. Publication Date: 2010 Sep |
Date Detail:
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Created Date: 2010-09-03 Completed Date: 2010-11-23 Revised Date: 2011-04-01 |
Medline Journal Info:
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Nlm Unique ID: 2985117R Medline TA: J Immunol Country: United States |
Other Details:
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Languages: eng Pagination: 3677-84 Citation Subset: AIM; IM |
Affiliation:
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Clinical Immunology Laboratory, First Affiliated Hospital, Soochow University, Suzhou, People's Republic of China. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adjuvants, Immunologic
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blood,
physiology*,
toxicity Animals Antigens, CD / blood, physiology* Antigens, CD80 / physiology Bacterial Outer Membrane Proteins / toxicity Cell Line Cells, Cultured Humans Immunity, Innate Inflammation Mediators / blood, physiology*, toxicity Interleukin-6 / blood Lipopolysaccharides / toxicity Macrophages / immunology, pathology, secretion Male Mice Mice, Inbred C3H Monocytes / immunology, pathology, secretion Receptors, Immunologic / blood, physiology* Sepsis / immunology*, microbiology, mortality, pathology* Toll-Like Receptor 2 / physiology Toll-Like Receptor 4 / physiology Tumor Necrosis Factor-alpha / blood |
| Chemical | |
Reg. No./Substance:
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0/Adjuvants, Immunologic; 0/Antigens, CD; 0/Antigens, CD80; 0/Bacterial Outer Membrane Proteins; 0/CD276 protein, human; 0/Cd276 protein, mouse; 0/IL6 protein, human; 0/Inflammation Mediators; 0/Interleukin-6; 0/Lipopolysaccharides; 0/Receptors, Immunologic; 0/TLR2 protein, human; 0/TLR4 protein, human; 0/Toll-Like Receptor 2; 0/Toll-Like Receptor 4; 0/Tumor Necrosis Factor-alpha |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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