IRF9 as a negative regulator involved in TRIF-mediated NF-κB pathway in a teleost fish, Miichthys miiuy

Mol Immunol. 2017 May:85:123-129. doi: 10.1016/j.molimm.2017.02.009. Epub 2017 Feb 23.

Abstract

Proinflammatory cytokines and type I IFNs were produced by TLR signaling and these responses are crucial for host defensive responses against pathogens. In order to avoid harmful and inappropriate inflammatory responses, there are multiple mechanisms to negatively regulate TLR signaling. In this paper, we have firstly studied IRF9 functions as a negative regulator involved in TRIF-mediated NF-κB pathway. Moreover, we found inhibitory effect of IRF9 primary depends on DBD domain. Interestingly, we also demonstrated that else mutants of IRF9, except for IRF9-ΔDBD, have different inhibitory effects upon TRIF-mediated NF-κB pathway. This study provides a novel evidence about the negatively regulation of innate immune signaling pathway in teleost fish. In addition, this finding provides new insights into the regulatory mechanism in mammals.

Keywords: IRF9; NF-κB; Negative regulation; TRIF; Teleost.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Vesicular Transport / immunology*
  • Adaptor Proteins, Vesicular Transport / metabolism
  • Animals
  • Blotting, Western
  • Immunity, Innate / immunology*
  • Immunohistochemistry
  • Interferon-Stimulated Gene Factor 3, gamma Subunit / immunology*
  • Interferon-Stimulated Gene Factor 3, gamma Subunit / metabolism
  • NF-kappa B / immunology*
  • NF-kappa B / metabolism
  • Perciformes / immunology*
  • Perciformes / metabolism
  • Polymerase Chain Reaction
  • Signal Transduction / immunology

Substances

  • Adaptor Proteins, Vesicular Transport
  • Interferon-Stimulated Gene Factor 3, gamma Subunit
  • NF-kappa B