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Related Concept Videos

Notch Signaling Pathway03:14

Notch Signaling Pathway

The Notch signaling pathway is a major intracellular signaling pathway that is highly conserved over a broad spectrum of metazoan species. It stands unique from other intracellular signaling mechanisms in animals because notch protein itself acts as the receptor as well as the primary signaling molecule.
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not until 1985...
Notch Signaling Pathway03:14

Notch Signaling Pathway

The Notch signaling pathway is a major intracellular signaling pathway that is highly conserved over a broad spectrum of metazoan species. It stands unique from other intracellular signaling mechanisms in animals because notch protein itself acts as the receptor as well as the primary signaling molecule.
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not until 1985...
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...
Cells of the Innate Immune Response01:28

Cells of the Innate Immune Response

The innate immune response is an immediate and non-specific response against pathogens, acting swiftly to prevent the spread of infections. The primary cells involved in this response are phagocytes and natural killer (NK) cells.
Phagocytes
Phagocytes police the peripheral tissues by removing cellular debris and responding to the invasion of foreign substances or pathogens. Many phagocytes attack and remove microorganisms even before lymphocytes detect them. The human body has two general...
Immune Surveillance by NK Cells and Phagocytes01:25

Immune Surveillance by NK Cells and Phagocytes

Immune surveillance is an integral part of the innate immune system, involving the continuous monitoring of peripheral tissues to detect and respond to pathogens, infected cells, or cancerous cells. This surveillance is conducted primarily by natural killer (NK) cells and phagocytes, which employ distinct but complementary mechanisms to identify and eliminate threats.
Natural Killer Cells: The Fast Responders
NK cells are large granular lymphocytes found in the blood and lymphatic system. These...
Role Of Notch Signalling In Intestinal Stem Cell Renewal01:12

Role Of Notch Signalling In Intestinal Stem Cell Renewal

Notch signaling was first discovered in Drosophila melanogaster, where it is involved in cell lineage differentiation. Notch signaling regulates the maintenance and differentiation of intestinal stem cells or ISCs by controlling the expression of atonal homolog 1 or Atoh1. Atoh1 directs cells to differentiate into secretory cells.
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...

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Related Experiment Video

Updated: Jun 6, 2026

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

Intracellular pathogen sensor NOD2 programs macrophages to trigger Notch1 activation.

Kushagra Bansal1, Kithiganahalli N Balaji

  • 1Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore 560012, India.

The Journal of Biological Chemistry
|December 16, 2010
PubMed
Summary

NOD2 programs macrophages to activate Notch1 signaling, crucial for anti-inflammatory responses. This pathway, involving PI3K and nitric oxide, resolves inflammation and enhances macrophage survival.

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Published on: May 21, 2018

Area of Science:

  • Immunology
  • Molecular Biology
  • Cell Signaling

Background:

  • Nucleotide-binding oligomerization domain-containing protein 2 (NOD2) is an intracellular sensor involved in inflammatory responses.
  • The precise molecular mechanisms underlying NOD2's role in regulating inflammation are not fully understood.
  • NOD2's involvement in various inflammatory diseases necessitates a deeper investigation into its signaling pathways.

Purpose of the Study:

  • To elucidate the molecular mechanisms by which NOD2 regulates anti-inflammatory responses.
  • To investigate the role of Notch1 signaling in NOD2-mediated immune responses.
  • To identify key signaling molecules and pathways involved in NOD2's function.

Main Methods:

  • Utilized genetic approaches and signaling perturbations in macrophage models.
  • Investigated the interaction between Notch1 and PI3K signaling pathways.
  • Assessed the role of inducible nitric oxide synthase (iNOS) in NOD2 signaling using knockout mice.

Main Results:

  • NOD2 stimulation triggers Notch1 signaling in macrophages, leading to the expression of anti-inflammatory mediators like COX-2/PGE(2) and IL-10.
  • Cross-talk between Notch1 and PI3K signaling is essential for NOD2-mediated immune gene expression.
  • Nitric oxide produced by iNOS is critical for NOD2-induced Notch1 activation and subsequent anti-inflammatory functions.

Conclusions:

  • NOD2 activates macrophages via the Notch1-PI3K signaling axis, promoting anti-inflammatory gene expression and macrophage survival.
  • This pathway is vital for resolving inflammation and protecting macrophages from apoptosis.
  • Findings provide a framework for understanding NOD2-associated inflammatory diseases and developing targeted therapies.