NQO1 inhibits the TLR-dependent production of selective cytokines by promoting IκB-ζ degradation.

ABSTRACT: NAD(P)H:quinone oxidoreductase 1 (NQO1) protects cells against oxidative stress and toxic quinones. In this study, we found a novel role of NQO1 in suppressing Toll-like receptor (TLR)-mediated innate immune responses. NQO1-deficient macrophages selectively produced excessive amounts of IL-6, IL-12, and GM-CSF on LPS stimulation, and the deletion of NQO1 in macrophages exacerbated LPS-induced septic shock. NQO1 interacted with the nuclear IκB protein IκB-ζ, which is essential for the TLR-mediated induction of a subset of secondary response genes, including IL-6, and promoted IκB-ζ degradation in a ubiquitin-dependent manner. We demonstrated that PDLIM2, known as the ubiquitin E3 ligase, participates in NQO1-dependent IκB-ζ degradation. NQO1 augmented the association between PDLIM2 and IκB-

SUBMITTER: Kimura A 

PROVIDER: S-EPMC6080903 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature