期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 106, 期 48, 页码 20388-20393出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0908698106
关键词
caspase-1; interleukin-1 beta; necrosis
资金
- American Cancer Society, administered through The Holden Comprehensive Cancer Center at the University of Iowa [IRG77-004-31]
- National Institutes of Health [K08 AI065517]
- Netherlands Organization for Scientific Research [916.56.168]
- Dutch Kidney foundation [C06.6023]
Dying cells are capable of activating the innate immune system and inducing a sterile inflammatory response. Here, we show that necrotic cells are sensed by the Nlrp3 inflammasome resulting in the subsequent release of the proinflammatory cytokine IL-1 beta. Necrotic cells produced by pressure disruption, hypoxic injury, or complement-mediated damage were capable of activating the Nlrp3 inflammasome. Nlrp3 inflammasome activation was triggered in part through ATP produced by mitochondria released from damaged cells. Neutrophilic influx into the peritoneum in response to necrotic cells in vivo was also markedly diminished in the absence of Nlrp3. Nlrp3-deficiency moreover protected animals against mortality, renal dysfunction, and neutrophil influx in an in vivo renal ischemic acute tubular necrosis model. These findings suggest that the inhibition of Nlrp3 inflammasome activity can diminish the acute inflammation and damage associated with tissue injury.
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