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

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-b. 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.

Phenotypic Alteration of BMDM In Vitro Using Small Interfering RNA

“…In IRF3 −/− macrophages, poly I:C failed to stimulate NO production [ 42 ]. Mechanistic experiments allowed authors to suggest that ERK and IRF3 coordinate induction of NO by macrophages in response to stimulation of TLR3 [ 43 ]. These data support our observations on the critical role of IRF3 in the induction of crucial macrophage polarization markers.…”

EGFR Activation Impairs Antiviral Activity of Interferon Signaling in Brain Microvascular Endothelial Cells During Japanese Encephalitis Virus Infection

“…When compared to mock-treated cells, a markedly impaired production of JEV viral RNA and E protein, as well as viral particles in U0126, was observed, but this change was not noticed in 17-AAG-treated hBMECs (Figures 6F-H). Previous reports have demonstrated that ERK negatively regulates the interferon signaling-mediated antiviral response (Yang and Ding, 2019;Freed et al, 2021). Therefore, the expression of interferons and ISGs was also measured with U0126 treatment in JEV-infected hBMECs.…”