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

Akihiro Kimura, Masayuki Kitajima, Kyoko Nishida, Satoshi Serada, Minoru Fujimoto, Tetsuji Naka, Yoshiaki Fujii-Kuriyama, Satoshi Sakamato, Takumi Ito, Hiroshi Handa, Takashi Tanaka, Akihiko Yoshimura, Harumi Suzuki

研究成果: Article査読

14 被引用数 (Scopus)


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-ζ, resulting in increased IκB-ζ 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.

ジャーナルJournal of Experimental Medicine
出版ステータスPublished - 2018 9月 1

ASJC Scopus subject areas

  • 医学(全般)


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