| Distinct roles of hepatocyte- and myeloid cell-derived IL-1 receptor antagonist during endotoxemia and sterile inflammation in mice. | |
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MedLine Citation:
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PMID: 20639493 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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IL-1R antagonist (IL-1Ra) is a natural inhibitor of the pleiotropic proinflammatory activities of IL-1. Although several reports described the effects of complete IL-1Ra deficiency, no study has examined the consequences of cell type-specific IL-1Ra inactivation during systemic inflammation. Previous in vitro data demonstrated high IL-1Ra production by hepatocytes and myeloid cells after endotoxin stimulation. In addition, hepatocyte IL-1Ra production is regulated as an acute-phase protein in vitro. In this study, we analyzed the production and functional role of hepatocyte- and myeloid cell-derived IL-1Ra during endotoxin-induced septic shock and acute IL-1beta-induced sterile inflammation. Using conditional IL-1Ra knockout mice, we showed that hepatocytes and myeloid cells are the two major cellular sources of circulating IL-1Ra in response to LPS. Interestingly, IL-1Ra production by myeloid cells, but not hepatocytes, is critical for survival during endotoxemia. Furthermore, we provide the first in vivo evidence demonstrating that IL-1Ra is produced as an acute-phase protein by hepatocytes during IL-1beta-induced inflammation and that hepatocyte-derived IL-1Ra functions as an endogenous negative feedback downregulating the proinflammatory effects of IL-1. Taken together, our observations define distinct roles for two major cellular sources of IL-1Ra in response to different types of systemic inflammatory stimuli in vivo. |
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Authors:
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Céline Lamacchia; Gaby Palmer; Loraine Bischoff; Emiliana Rodriguez; Dominique Talabot-Ayer; Cem Gabay |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-07-16 |
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 Aug |
Date Detail:
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Created Date: 2010-08-05 Completed Date: 2010-09-22 Revised Date: - |
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: 2516-24 Citation Subset: AIM; IM |
Affiliation:
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Division of Rheumatology, University Hospitals of Geneva, Geneva, Switzerland. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Acute-Phase Proteins
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genetics,
physiology Animals Endotoxemia / blood*, physiopathology Enzyme-Linked Immunosorbent Assay Female Hepatocytes / metabolism* Immunohistochemistry Inflammation / blood*, chemically induced, physiopathology Interleukin 1 Receptor Antagonist Protein / blood*, genetics, physiology Lipopolysaccharides Liver / metabolism Lung / metabolism Male Mice Mice, Inbred C57BL Mice, Knockout Myeloid Cells / metabolism* Spleen / metabolism Survival Analysis |
| Chemical | |
Reg. No./Substance:
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0/Acute-Phase Proteins; 0/Interleukin 1 Receptor Antagonist Protein; 0/Lipopolysaccharides |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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