MEK/ERK MAP kinase limits poly I:C-induced antiviral gene expression in RAW264.7 macrophages by reducing interferon-beta expression

FEBS Lett. 2021 Nov;595(21):2665-2674. doi: 10.1002/1873-3468.14200. Epub 2021 Oct 11.

Abstract

Toll-like receptor 3 (TLR3) recognizes viral double-stranded RNA (or the synthetic dsRNA analog poly I:C) and induces a signal transduction pathway that results in activation of transcription factors that induce expression of antiviral genes including type I interferon (IFN-I). Secreted IFN-I positively feeds back to amplify antiviral gene expression. In this report, we study the role of MEK/ERK MAP kinase in modulating antiviral gene expression downstream of TLR3. We find MEK/ERK is a negative regulator of antiviral gene expression by limiting expression of IFN-β. However, MEK/ERK does not limit antiviral responses downstream of the type I interferon receptor. These findings provide insights into regulatory mechanisms of antiviral gene expression and reveal potential targets for modulating antiviral immunity.

Keywords: EGFR; ERK; IRF3; ISG; RAW264.7; TLR3; interferon; poly I:C.

Publication types

  • Letter
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Extracellular Signal-Regulated MAP Kinases / genetics
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Gene Expression Regulation / drug effects
  • Interferon-beta* / genetics
  • Interferon-beta* / metabolism
  • MAP Kinase Signaling System / drug effects
  • Macrophages* / drug effects
  • Macrophages* / immunology
  • Macrophages* / metabolism
  • Macrophages* / virology
  • Mice
  • Poly I-C* / pharmacology
  • RAW 264.7 Cells
  • Toll-Like Receptor 3* / genetics
  • Toll-Like Receptor 3* / metabolism

Substances

  • Poly I-C
  • Interferon-beta
  • Toll-Like Receptor 3
  • TLR3 protein, mouse
  • Extracellular Signal-Regulated MAP Kinases