| The hydroxylase inhibitor dimethyloxallyl glycine attenuates endotoxic shock via alternative activation of macrophages and IL-10 production by B1 cells. | |
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MedLine Citation:
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PMID: 21844787 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Localized tissue hypoxia is a feature of infection and inflammation, resulting in the upregulation of the transcription factors hypoxia-inducible factor 1α and nuclear factor κB (NF-κB) via inhibition of oxygen sensing hydroxylase enzymes. Previous studies have demonstrated a beneficial role for the hydroxylase inhibitor dimethyloxallyl glycine (DMOG) in inflammatory conditions, including experimental colitis, by regulating the activity of hypoxia-inducible factor 1 and NF-κB. We have demonstrated in vivo that pretreatment with DMOG attenuates systemic LPS-induced activation of the NF-κB pathway. Furthermore, mice treated with DMOG had significantly increased survival in LPS-induced shock. Conversely, in models of polymicrobial sepsis, DMOG exacerbates disease severity. Dimethyloxallyl glycine treatment of mice promotes M2 polarization in macrophages within the peritoneal cavity, resulting in the downregulation of proinflammatory cytokines such as TNF-α. In addition, in vivo DMOG treatment upregulates IL-10 expression, specifically in the peritoneal B1 cell population. This study demonstrates cell type-specific roles for hydroxylase inhibition in vivo and provides insight into the mechanism underlying the protection conveyed by DMOG in models of endotoxic shock. |
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Authors:
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Emily Hams; Sean P Saunders; Eoin P Cummins; Aisling O'Connor; Murtaza T Tambuwala; William M Gallagher; Annette Byrne; Antonio Campos-Torres; Paul M Moynagh; Christian Jobin; Cormac T Taylor; Padraic G Fallon |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Shock (Augusta, Ga.) Volume: 36 ISSN: 1540-0514 ISO Abbreviation: Shock Publication Date: 2011 Sep |
Date Detail:
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Created Date: 2011-08-16 Completed Date: 2012-02-02 Revised Date: 2012-09-28 |
Medline Journal Info:
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Nlm Unique ID: 9421564 Medline TA: Shock Country: United States |
Other Details:
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Languages: eng Pagination: 295-302 Citation Subset: IM |
Affiliation:
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Institute of Molecular Medicine, Trinity College, Dublin, Ireland. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Amino Acids, Dicarboxylic
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therapeutic use* Animals Flow Cytometry Immunoblotting Interleukin-10 / metabolism Lipopolysaccharides / toxicity Macrophages / drug effects*, metabolism* Mice Mice, Inbred BALB C Mice, Inbred C57BL Mixed Function Oxygenases / antagonists & inhibitors NF-kappa B / metabolism Polymerase Chain Reaction Receptors, Interleukin-10 / blood Sepsis / drug therapy Shock, Septic / chemically induced, drug therapy* |
| Grant Support | |
ID/Acronym/Agency:
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R01 DK047700-07/DK/NIDDK NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Amino Acids, Dicarboxylic; 0/Lipopolysaccharides; 0/NF-kappa B; 0/Receptors, Interleukin-10; 130068-27-8/Interleukin-10; 5262-39-5/oxalylglycine; EC 1.-/Mixed Function Oxygenases |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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