期刊
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
卷 21, 期 10, 页码 1732-1744出版社
AMER SOC NEPHROLOGY
DOI: 10.1681/ASN.2010020143
关键词
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资金
- Canadian Institutes for Health Research
- Canadian Foundation for Innovation
- Alberta Heritage Foundation
- Tier II Canada Research Chair
Inflammation significantly contributes to the progression of chronic kidney disease (CKD). Inflammasome-dependent cytokines, such as IL-1 beta and IL-18, play a role in CKD, but their regulation during renal injury is unknown. Here, we analyzed the processing of caspase-1, IL-1 beta, and IL-18 after unilateral ureteral obstruction (UUO) in mice, which suggested activation of the NIrp3 inflammasome during renal injury. Compared with wild-type mice, NIrp3(-/-) mice had less tubular injury, inflammation, and fibrosis after UUO, associated with a reduction in caspase-1 activation and maturation of IL-1 beta and IL-18; these data confirm that the NIrp3 inflammasome upregulates these cytokines in the kidney during injury. Bone marrow chimeras revealed that NIrp3 mediates the injurious/inflammatory processes in both hematopoietic and nonhematopoietic cellular compartments. In tissue from human renal biopsies, a wide variety of nondiabetic kidney diseases exhibited increased expression of NLRP3 mRNA, which correlated with renal function. Taken together, these results strongly support a role for NLRP3 in renal injury and identify the inflammasome as a possible therapeutic target in the treatment of patients with progressive CKD.
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