| First Author | Kimura A | Year | 2018 |
| Journal | J Exp Med | Volume | 215 |
| Issue | 8 | Pages | 2197-2209 |
| PubMed ID | 29934320 | Mgi Jnum | J:265840 |
| Mgi Id | MGI:6201871 | Doi | 10.1084/jem.20172024 |
| Citation | Kimura A, et al. (2018) NQO1 inhibits the TLR-dependent production of selective cytokines by promoting IkappaB-zeta degradation. J Exp Med 215(8):2197-2209 |
| abstractText | 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 IkappaB protein IkappaB-zeta, which is essential for the TLR-mediated induction of a subset of secondary response genes, including IL-6, and promoted IkappaB-zeta degradation in a ubiquitin-dependent manner. We demonstrated that PDLIM2, known as the ubiquitin E3 ligase, participates in NQO1-dependent IkappaB-zeta degradation. NQO1 augmented the association between PDLIM2 and IkappaB-zeta, resulting in increased IkappaB-zeta degradation. Collectively, this study describes a mechanism of the NQO1-PDLIM2 complex as a novel and important regulator in the innate immune signaling and suggests the therapeutic potential of NQO1 in TLR-mediated inflammation and disorders. |
