Related Experiment Video

Updated: Aug 17, 2026

Activation and Measurement of NLRP3 Inflammasome Activity Using IL-1β in Human Monocyte-derived Dendritic Cells
09:04

Activation and Measurement of NLRP3 Inflammasome Activity Using IL-1β in Human Monocyte-derived Dendritic Cells

Published on: May 22, 2014

IFN-alpha beta reconstitutes the deficiency in lipid A-activated AKR macrophages for nitric oxide synthase

H Jiang1, J A Rummage, A Zhou

  • 1Oklahoma Medical Research Foundation, Noble Center for Biomedical Research, Oklahoma City 73104, USA.

Journal of Immunology (Baltimore, Md. : 1950)
|July 1, 1996
PubMed

Insights

AKR mouse macrophages show a defect in nitric oxide (NO) production in response to lipid A, which is restored by interferon-alpha beta (IFN-αβ). This suggests IFN-αβ is crucial for macrophage activation and NO synthesis.

Area of Science:

  • Immunology
  • Cell Biology
  • Molecular Biology

Background:

  • AKR mouse peritoneal macrophages (PM) exhibit impaired nitric oxide (NO)-mediated tumor cytotoxicity in response to lipid A.
  • This defect is linked to reduced C1q synthesis and can be restored by exogenous IFN-gamma or C1q.

Purpose of the Study:

  • To investigate the role of interferon-alpha beta (IFN-αβ) in modulating macrophage nitric oxide synthase (NOS) induction by lipid A in AKR-PM.
  • To elucidate the molecular mechanisms underlying the refractoriness of AKR-PM to lipid A stimulation.

Main Methods:

  • Comparison of IFN-αβ production between AKR-PM and responsive C3H-PM upon lipid A stimulation.
  • Assessment of NOS mRNA synthesis and NO generation in AKR-PM with and without exogenous IFN-αβ.
  • Analysis of TNF-alpha type II receptor (TNF-RII) mRNA expression and TNF-alpha bioactivity.

Main Results:

  • AKR-PM produced significantly lower levels of IFN-αβ compared to C3H-PM in response to lipid A.
  • AKR-PM failed to increase NOS mRNA and NO generation upon lipid A exposure, despite normal TNF-alpha levels.
  • Exogenous IFN-αβ fully reconstituted NOS mRNA synthesis and NO release in AKR-PM.
  • The defect was associated with reduced IFN-αβ secretion, leading to decreased TNF-RII mRNA expression and impaired autocrine NOS induction.

Conclusions:

  • Insufficient endogenous IFN-αβ secretion is the primary cause of AKR-PM refractoriness to lipid A-induced NOS.
  • IFN-αβ plays a critical role in upregulating macrophage TNF-RII expression for autocrine NOS induction during lipid A stimulation.

More Related Videos

Isolation Protocol of Mouse Monocyte-derived Dendritic Cells and Their Subsequent In Vitro Activation with Tumor Immune Complexes11:48

Isolation Protocol of Mouse Monocyte-derived Dendritic Cells and Their Subsequent In Vitro Activation with Tumor Immune Complexes

Published on: May 31, 2018

A Macrophage Reporter Cell Assay to Examine Toll-Like Receptor-Mediated NF-kB/AP-1 Signaling on Adsorbed Protein Layers on Polymeric Surfaces07:55

A Macrophage Reporter Cell Assay to Examine Toll-Like Receptor-Mediated NF-kB/AP-1 Signaling on Adsorbed Protein Layers on Polymeric Surfaces

Published on: January 7, 2020

Related Concept Videos

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...
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...
Acute Inflammation I: Inflammatory Response01:26

Acute Inflammation I: Inflammatory Response

Acute inflammation is a rapid, short-lived physiological response to tissue injury or infection, designed to eliminate harmful agents and initiate repair. This tightly regulated process typically lasts from minutes to several days and is triggered by factors such as microbial invasion, physical trauma, or chemical injury.Recognition and Mediator ReleaseThe inflammatory response begins when resident immune cells—such as mast cells, macrophages, and dendritic cells—detect damage-associated...