Uric acid promotes an acute inflammatory response to sterile cell death in mice
UMass Chan Affiliations
Department of PathologyDocument Type
Journal ArticlePublication Date
2010-05-27Keywords
AnimalsCell Death
Cells
Immune System
Inflammation
Mice
Mice, Inbred C57BL
Mice, Inbred Strains
Mice, Transgenic
Necrosis
Uric Acid
Immunopathology
Life Sciences
Medicine and Health Sciences
Pathology
Metadata
Show full item recordAbstract
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.Source
J Clin Invest. 2010 Jun 1;120(6):1939-49. doi: 10.1172/JCI40124. Epub 2010 May 24. Link to article on publisher's siteDOI
10.1172/JCI40124Permanent Link to this Item
http://hdl.handle.net/20.500.14038/39424PubMed ID
20501947; 20501947Related Resources
Link to Article in PubMedae974a485f413a2113503eed53cd6c53
10.1172/JCI40124