Related Experiment Video

Updated: Aug 8, 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

Human/mouse interleukin-1 receptor/receptor accessory protein interactions in IL-1beta-induced NFkappaB activation

S Layé1, J Lundkvist, T Bartfai

  • 1Department of Neurochemistry and Neurotoxicology, Stockholm University, Sweden.

FEBS Letters
|July 14, 1998
PubMed

Insights

Functional complexes between human IL-1RI (interleukin-1 receptor type I) and murine IL-1R accessory protein (mIL-1RAcP) were formed. Both homologous and heterologous interactions support NFkappaB translocation, but with distinct signaling patterns.

Area of Science:

  • Immunology
  • Cell Biology
  • Molecular Biology

Background:

  • Interleukin-1 receptor type I (IL-1RI) and IL-1R accessory protein (IL-1RAcP) form receptor complexes crucial for IL-1 signaling.
  • Understanding the formation and function of heterologous complexes between human and murine IL-1 receptor components is important for comparative immunology and drug development.

Purpose of the Study:

  • To investigate the formation of functional heterologous complexes between human IL-1RI and murine IL-1RAcP.
  • To determine how these heterologous interactions influence downstream signaling pathways, specifically NF-kappaB activation.

Main Methods:

  • Utilized human embryonic kidney 293 (HEK 293) cells and murine fibroblast C127 cells.
  • Employing stable transfection to express human IL-1RI in C127 cells (C127-hIL-1RI).
  • Assessed NF-kappaB p50/p65 and p65/p65 heterodimer activation in response to IL-1beta stimulation.

Main Results:

  • In non-transfected C127 cells, IL-1beta signaled via the murine IL-1RI-mIL-1RAcP complex, activating NFkappaB p50/p65 heterodimers.
  • In C127-hIL-1RI cells, IL-1beta signaled through the human IL-1RI, activating both p65/p65 and p50/p65 NFkappaB complexes.
  • Activation of NFkappaB p65/p65 was dependent on mIL-1RAcP in the heterologous system.

Conclusions:

  • Both homologous (murine-murine) and heterologous (human-murine) IL-1RI-IL-1RAcP interactions effectively support NF-kappaB translocation.
  • Distinct signaling patterns arise from homologous versus heterologous IL-1 receptor complex formation.
  • These findings highlight the potential for cross-species receptor interactions and their differential signaling outcomes.

More Related Videos

An ELISA Based Binding and Competition Method to Rapidly Determine Ligand-receptor Interactions08:40

An ELISA Based Binding and Competition Method to Rapidly Determine Ligand-receptor Interactions

Published on: March 14, 2016

A Guide to Production, Crystallization, and Structure Determination of Human IKK1/α11:27

A Guide to Production, Crystallization, and Structure Determination of Human IKK1/α

Published on: November 2, 2018

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...
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...
Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
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...
The JAK-STAT Signaling Pathway01:20

The JAK-STAT Signaling Pathway

Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as  SH2...
Intracellular Signaling Affects Focal Adhesions01:17

Intracellular Signaling Affects Focal Adhesions

Integrins act both as extracellular input receivers and as intracellular processing activators. As their name suggests, integrins are entirely integrated into the membrane structure. Their hydrophobic membrane-spanning regions interact with the phospholipid bilayer's hydrophobic region. These membrane receptors provide extracellular attachment sites for effectors like hormones and growth factors. They activate intracellular response cascades when their effectors are bound and active.
Some...