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

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.
Shawn M Freed 1 Danielle S Baldi 1 Jason A Snow 1 Sierra R Athen 1 Zachary P Guinn 2 T Scott Pinkerton 1 Thomas M Petro 2 Tyler C Moore 1
Affiliations

Affiliations

  • 1 Department of Biology, College of Science and Technology, Bellevue University, NE, USA.
  • 2 Department of Oral Biology, College of Dentistry, University of Nebraska Medical Center, Lincoln, NE, USA.
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.

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