Interferon regulatory factor 3 plays a role in macrophage responses to interferon-γ.

Abstract:

:IFN-γ produced during viral infections activates the IFN-γ receptor (IFNGR) complex for STAT1 transcriptional activity leading to expression of Interferon Regulatory Factors (IRF). Simultaneous activation of TBK/IKKε via TLR3 during viral infections activates the transcription factor IRF3. Together these transcription factors contributes to expression of intracellular proteins (e.g. ISG49, ISG54) and secreted proteins (e.g. IFN-β, IP-10, IL-15) that are essential to innate antiviral immunity. Here we examined the role of IRF3 in expression of innate anti-viral proteins produced in response to IFN-γ plus TLR3 agonist. Wild-type (WT) and IRF3KO RAW264.7 cells, each with ISG54-promoter-luciferase reporter vectors, were stimulated with IFN-γ, poly I:C, or both together. ISG54 promoter activity was significantly reduced in IRF3KO RAW264.7 cells responding to IFN-γ, poly I:C, or IFN-γ plus poly I:C, compared with WT RAW264.7 cells. These data were confirmed with western blot and qRT-PCR. Primary macrophages and dendritic cells (DCs) from IRF3KO mice also showed decreased ISG54 in response to IFN-γ, poly I:C, or IFN-γ plus poly I:C compared with those from WT mice. Moreover, pharmacological inhibition of TBK/IKKε significantly reduced ISG54 promoter activity in response to IFN-γ, poly I:C, or IFN-γ plus poly I:C. Similarly, expression of ISG49 and IL-15, but not IP-10, was impaired in IRF3KO RAW264.7 cells responding to IFN-γ or poly I:C, which also had impaired STAT1 phosphorylation and IRF1 expression. These data show that IRF3 contributes to IFN-γ/IFNGR signaling for expression of innate anti-viral proteins in macrophages.

journal_name

Immunobiology

journal_title

Immunobiology

authors

Guinn ZP,Petro TM

doi

10.1016/j.imbio.2019.04.004

subject

Has Abstract

pub_date

2019-07-01 00:00:00

pages

565-574

issue

4

eissn

0171-2985

issn

1878-3279

pii

S0171-2985(19)30092-0

journal_volume

224

pub_type

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