Document Detail


Uric acid promotes an acute inflammatory response to sterile cell death in mice.
MedLine Citation:
PMID:  20501947     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Necrosis stimulates inflammation, and this response is medically relevant because it contributes to the pathogenesis of a number of diseases. It is thought that necrosis stimulates inflammation because dying cells release proinflammatory molecules that are recognized by the immune system. However, relatively little is known about the molecular identity of these molecules and their contribution to responses in vivo. Here, we investigated the role of uric acid in the inflammatory response to necrotic cells in mice. We found that dead cells not only released intracellular stores of uric acid but also produced it in large amounts postmortem as nucleic acids were degraded. Using newly developed Tg mice that have reduced levels of uric acid either intracellularly and/or extracellularly, we found that uric acid depletion substantially reduces the cell death-induced inflammatory response. Similar results were obtained with pharmacological treatments that reduced uric acid levels either by blocking its synthesis or hydrolyzing it in the extracellular fluids. Importantly, uric acid depletion selectively inhibited the inflammatory response to dying cells but not to microbial molecules or sterile irritant particles. Collectively, our data identify uric acid as a proinflammatory molecule released from dying cells that contributes significantly to the cell death-induced inflammatory responses in vivo.
Authors:
Hajime Kono; Chun-Jen Chen; Fernando Ontiveros; Kenneth L Rock
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2010-05-24
Journal Detail:
Title:  The Journal of clinical investigation     Volume:  120     ISSN:  1558-8238     ISO Abbreviation:  J. Clin. Invest.     Publication Date:  2010 Jun 
Date Detail:
Created Date:  2010-06-02     Completed Date:  2010-06-21     Revised Date:  2014-09-11    
Medline Journal Info:
Nlm Unique ID:  7802877     Medline TA:  J Clin Invest     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1939-49     Citation Subset:  AIM; IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Cell Death / drug effects,  immunology
Cells / metabolism
Immune System / metabolism*
Inflammation / immunology,  metabolism*
Mice
Mice, Inbred C57BL
Mice, Inbred Strains
Mice, Transgenic
Necrosis
Uric Acid / metabolism*,  pharmacology*
Grant Support
ID/Acronym/Agency:
DK32520/DK/NIDDK NIH HHS; R01 AI043543/AI/NIAID NIH HHS; R01 AI078287/AI/NIAID NIH HHS
Chemical
Reg. No./Substance:
268B43MJ25/Uric Acid
Comments/Corrections

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