| First Author | Vilaysane A | Year | 2010 |
| Journal | J Am Soc Nephrol | Volume | 21 |
| Issue | 10 | Pages | 1732-44 |
| PubMed ID | 20688930 | Mgi Jnum | J:185911 |
| Mgi Id | MGI:5430486 | Doi | 10.1681/ASN.2010020143 |
| Citation | Vilaysane A, et al. (2010) The NLRP3 inflammasome promotes renal inflammation and contributes to CKD. J Am Soc Nephrol 21(10):1732-44 |
| abstractText | Inflammation significantly contributes to the progression of chronic kidney disease (CKD). Inflammasome-dependent cytokines, such as IL-1beta 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-1beta, and IL-18 after unilateral ureteral obstruction (UUO) in mice, which suggested activation of the Nlrp3 inflammasome during renal injury. Compared with wild-type mice, Nlrp3(-/-) mice had less tubular injury, inflammation, and fibrosis after UUO, associated with a reduction in caspase-1 activation and maturation of IL-1beta and IL-18; these data confirm that the Nlrp3 inflammasome upregulates these cytokines in the kidney during injury. Bone marrow chimeras revealed that Nlrp3 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. |
