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

Shawn M. Freed, Danielle S. Baldi, Jason A. Snow, Sierra R. Athen, Zachary P. Guinn, T. Scott Pinkerton, Thomas M. Petro, Tyler C. Moore

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)2665-2674
Number of pages10
JournalFEBS Letters
Volume595
Issue number21
DOIs
StatePublished - Nov 2021

Keywords

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

ASJC Scopus subject areas

  • Biophysics
  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology

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