| SphK1 regulates proinflammatory responses associated with endotoxin and polymicrobial sepsis. | |
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MedLine Citation:
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PMID: 20522778 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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During sepsis, activation of phagocytes leads to the overproduction of proinflammatory cytokines, causing systemic inflammation. Despite substantial information regarding the underlying molecular mechanisms that lead to sepsis, several elements in the pathway remain to be elucidated. We found that the enzyme sphingosine kinase 1 (SphK1) is up-regulated in stimulated human phagocytes and in peritoneal phagocytes of patients with severe sepsis. Blockade of SphK1 inhibited phagocyte production of endotoxin-induced proinflammatory cytokines. We observed protection against sepsis in mice treated with a specific SphK1 inhibitor that was enhanced by treatment with a broad-spectrum antibiotic. These results demonstrated a critical role for SphK1 in endotoxin signaling and sepsis-induced inflammatory responses and suggest that inhibition of SphK1 is a potential therapy for septic shock. |
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Authors:
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Padmam Puneet; Celestial T Yap; Lingkai Wong; Yulin Lam; Dow Rhoon Koh; Shabbir Moochhala; Josef Pfeilschifter; Andrea Huwiler; Alirio J Melendez |
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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: Science (New York, N.Y.) Volume: 328 ISSN: 1095-9203 ISO Abbreviation: Science Publication Date: 2010 Jun |
Date Detail:
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Created Date: 2010-06-04 Completed Date: 2010-06-16 Revised Date: 2011-10-24 |
Medline Journal Info:
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Nlm Unique ID: 0404511 Medline TA: Science Country: United States |
Other Details:
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Languages: eng Pagination: 1290-4 Citation Subset: IM |
Affiliation:
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Department of Physiology, National University of Singapore, 117597 Singapore. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Adolescent Adult Aged Aged, 80 and over Animals Bacterial Proteins / immunology Cytokines / blood, metabolism* Endotoxins Enzyme Activation Enzyme Inhibitors / pharmacology, therapeutic use Female Humans Inflammation* Lipopolysaccharides / immunology Lipoproteins / immunology Macrophages / enzymology, immunology Macrophages, Peritoneal / enzymology*, immunology Male Mice Middle Aged NF-kappa B / metabolism Neutrophils / enzymology*, immunology Peritonitis / enzymology, immunology Phosphotransferases (Alcohol Group Acceptor) / antagonists & inhibitors, genetics, metabolism* Protein Kinase C-delta / metabolism RNA Interference Sepsis / drug therapy, enzymology, immunology* Shock, Septic / enzymology, immunology* Signal Transduction Up-Regulation Young Adult |
| Grant Support | |
ID/Acronym/Agency:
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//Medical Research Council |
| Chemical | |
Reg. No./Substance:
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0/Bacterial Proteins; 0/Cytokines; 0/Endotoxins; 0/Enzyme Inhibitors; 0/Lipopolysaccharides; 0/Lipoproteins; 0/NF-kappa B; EC 2.7.1.-/Phosphotransferases (Alcohol Group Acceptor); EC 2.7.1.-/sphingosine kinase; EC 2.7.11.13/Protein Kinase C-delta |
| Comments/Corrections | |
Comment In:
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Science. 2011 Oct 21;334(6054):310
[PMID:
22021836
]
Nat Rev Immunol. 2010 Jul;10(7):464 [PMID: 20589990 ] Nat Rev Drug Discov. 2010 Jul;9(7):516-7 [PMID: 20592744 ] |
Erratum In:
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Science. 2011 Jan 14;331(6014):147 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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