Uromodulin triggers IL-1β-dependent innate immunity via the NLRP3 inflammasome.

ABSTRACT: Uromodulin/Tamm-Horsfall protein is not immunostimulatory in the tubular lumen, but through unknown mechanisms it can activate dendritic cells and promote inflammation in the renal interstitium. Here, we noted that uromodulin isolated from human urine aggregates to large, irregular clumps with a crystal-like ultrastructure. These uromodulin nanoparticles activated isolated human monocytes to express costimulatory molecules and to secrete the mature proinflammatory cytokines, including IL-1β. Full release of IL-1β in response to uromodulin depended on priming of pro-IL-1β expression by Toll-like receptors, TNF-α, or IL-1α. In addition, uromodulin-induced secretion of mature IL-1β depended on the NLRP3 inflammasome, its linker molecule ASC, and pro-IL-1β cleavage by caspase-1. Activation of

SUBMITTER: Darisipudi MN 

PROVIDER: S-EPMC3482735 | biostudies-literature | 2012 Nov

REPOSITORIES: biostudies-literature