Inhibitor of NFκB Kinase Subunit 2 Blockade Hinders the Initiation but Aggravates the Progression of Crescentic GN.

ABSTRACT: The NFκB transcription factor family facilitates the activation of dendritic cells (DCs) and CD4(+) T helper (Th) cells, which are important for protective adaptive immunity. Inappropriate activation of these immune cells may cause inflammatory disease, and NFκB inhibitors are promising anti-inflammatory drug candidates. Here, we investigated whether inhibiting the NFκB-inducing kinase IKK2 can attenuate crescentic GN, a severe DC- and Th cell-dependent kidney inflammatory disease. Prophylactic pharmacologic IKK2 inhibition reduced DC and Th cell activation and ameliorated nephrotoxic serum-induced GN in mice. However, therapeutic IKK2 inhibition during ongoing disease aggravated the nephritogenic immune response and disease symptoms. This effect resulted from the renal loss of regulatory

SUBMITTER: Gotot J 

PROVIDER: S-EPMC4926984 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature