Related Experiment Video

Updated: May 9, 2026

Application of Genetically Encoded Fluorescent Nitric Oxide (NO•) Probes, the geNOps, for Real-time Imaging of NO• Signals in Single Cells
08:32

Application of Genetically Encoded Fluorescent Nitric Oxide (NO•) Probes, the geNOps, for Real-time Imaging of NO• Signals in Single Cells

Published on: March 16, 2017

IRF3 and ERK MAP-kinases control nitric oxide production from macrophages in response to poly-I:C

Tyler C Moore1, Thomas M Petro

  • 1School of Biological Sciences, University of Nebraska-Lincoln, Lincoln, NE, USA.

FEBS Letters
|July 30, 2013
PubMed

Insights

Interferon regulatory factor 3 (IRF3) and ERK MAP-kinases are crucial for nitric oxide (NO) production in macrophages responding to viral mimicry. These factors coordinate NO induction via Toll-like receptor 3 (TLR3) signaling.

Area of Science:

  • Immunology
  • Virology
  • Cellular Signaling

Background:

  • Nitric oxide (NO) plays a key role in innate antiviral immunity and immune pathology.
  • The precise transcriptional and signaling pathways governing NO production remain incompletely understood.

Purpose of the Study:

  • To elucidate the key factors involved in macrophage nitric oxide (NO) production upon stimulation with a Toll-like receptor 3 (TLR3) agonist.

Main Methods:

  • Macrophages were stimulated with poly I:C (a TLR3 agonist).
  • The roles of Interferon Regulatory Factor 3 (IRF3), ERK MAP-kinases, and Protein Kinase RNA-activated (PKR) in NO production were investigated.
  • IRF3 knockout and knockdown models were utilized to assess cytokine-mediated effects.

Main Results:

  • IRF3, ERK MAP-kinases, and PKR were identified as essential for NO production in response to poly I:C.
  • ERK signaling may induce NO via IRF3 phosphorylation (serine-171) and expression of IL-6 and IFN-β.
  • While IL-6 and IFN-β contribute, they induced less NO in the absence of functional IRF3.

Conclusions:

  • ERK and IRF3 act in coordination to regulate macrophage NO induction following TLR3 stimulation.
  • This provides critical insight into the molecular mechanisms of innate antiviral responses.
Keywords:
BL/6C57BL/6 miceERKERK MAP-kinaseIRF3IRF3 deficient miceIRF3KOInterferon response factor-3Interleukin-6LPSMacrophagesNF-κBNONitric oxideODNPI3KPKRPoly I:CTIRTIR domain-containing adaptor-inducing IFN-βTLRTRIFextracellular signal related kinaseinterferon response factor 3lipopolysaccharidenitric oxidenuclear factor κ-Boligodeoxynucleotidephosphoinositide-3-kinaseprotein kinase Rtoll like receptortoll/IL-1 receptor

More Related Videos

A High Resolution Method to Monitor Phosphorylation-dependent Activation of IRF311:44

A High Resolution Method to Monitor Phosphorylation-dependent Activation of IRF3

Published on: January 24, 2016

Visualization of Vascular Ca2+ Signaling Triggered by Paracrine Derived ROS07:33

Visualization of Vascular Ca2+ Signaling Triggered by Paracrine Derived ROS

Published on: December 21, 2011

Related Concept Videos

Nitric Oxide Signaling Pathway01:28

Nitric Oxide Signaling Pathway

Nitric oxide (NO), an inorganic gas, acts as a potent second messenger in most animal and plant tissues. NO diffuses out of the cells that produce it and enters the neighboring cells to generate a downstream response. NO synthase (NOS) catalyzes NO production by the deamination of the amino acid arginine. There are three isoforms of NOS. Endothelial cells have endothelial NOS (eNOS), nerve and muscle cells have neuronal NOS (nNOS), and macrophages produce inducible NOS (iNOS) upon exposure to...
Regulation of the Unfolded Protein Response01:31

Regulation of the Unfolded Protein Response

Inositol-requiring kinase one or IRE1 is the most conserved eukaryotic unfolded protein response (UPR) receptor. It is a type I transmembrane protein kinase receptor with a distinctive site-specific RNase activity. As the binding mechanics of the misfolded proteins with the N-terminal domain of IRE-1 are unclear, three binding models — direct, indirect, and allosteric -- are proposed for receptor activation. Nevertheless, it is known that once a misfolded protein associates with IRE1, it...
NF-κB-dependent Signaling Pathway02:26

NF-κB-dependent Signaling Pathway

The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The heterodimer of NF-κB...
MAPK Signaling Cascades01:07

MAPK Signaling Cascades

Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
IP3/DAG Signaling Pathway01:11

IP3/DAG Signaling Pathway

Membrane lipids such as phosphatidylinositol (PI) are precursors for several membrane-bound and soluble second messengers. Specific kinases phosphorylate PI and produce phosphorylated inositol phospholipids. One such inositol phospholipids are the  phosphatidylinositol-4,5 bisphosphate [PI(4,5)P2], present in the inner half of the lipid bilayer. Upon ligand binding, GPCR stimulates Gq proteins to turn on phospholipase Cꞵ. Activated phospholipase Cꞵ cleaves PI(4,5)P2 and produces two-second...
Regulation of Angiogenesis and Blood Supply01:24

Regulation of Angiogenesis and Blood Supply

Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits.  Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl hydroxylase and factor...