Related Experiment Video

Updated: Jul 14, 2026

Isolation Protocol of Mouse Monocyte-derived Dendritic Cells and Their Subsequent In Vitro Activation with Tumor Immune Complexes
11:48

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

Published on: May 31, 2018

RIP2 mediates LPS-induced p38 and IkappaBalpha signaling including IL-12 p40 expression in human monocyte-derived

Nurguel Usluoglu1, Jovan Pavlovic, Karin Moelling

  • 1Institute of Medical Virology, University of Zurich, Zurich, Switzerland.

European Journal of Immunology
|June 21, 2007
PubMed

Insights

This study reveals Raf kinase activates receptor-interacting protein 2 (RIP2) to control Interleukin-12 (IL-12) production in dendritic cells stimulated by lipopolysaccharide (LPS). This pathway is crucial for initiating Th1 immune responses.

Area of Science:

  • Immunology
  • Cell Biology
  • Molecular Signaling

Background:

  • Interleukin-12 (IL-12) is essential for Th1 immune responses.
  • Dendritic cells (DCs) produce IL-12 upon stimulation with lipopolysaccharide (LPS).
  • LPS-induced IL-12 expression involves PI3K, MAPK, and NF-kappaB signaling pathways.

Purpose of the Study:

  • To investigate the role of the kinase Raf in LPS-induced IL-12 expression in human DCs.
  • To elucidate the specific signaling pathway mediating Raf's effect on IL-12 production.

Main Methods:

  • Utilized specific inhibitors for MAPK pathways to study signaling cascades.
  • Employed small interfering RNA (siRNA) to knock down receptor-interacting protein 2 (RIP2).
  • Assessed the impact of RIP2 knockdown on IL-12 p40 expression and upstream signaling molecules.

Main Results:

  • Raf kinase regulates IL-12 subunit p40 expression in LPS-stimulated human DCs.
  • Raf's regulation occurs via receptor-interacting protein 2 (RIP2), not the kinase MEK.
  • Knockdown of RIP2 inhibited LPS-dependent IL-12 p40 expression and reduced phosphorylation of p38 MAPK, ERK, and IkappaBalpha.

Conclusions:

  • LPS stimulation in human DCs activates a signal cascade involving Raf-dependent activation of RIP2.
  • This pathway leads to the expression of IL-12 p40, a critical component for Th1 immune responses.
  • RIP2 acts as a key mediator in the LPS-induced signaling pathway for IL-12 production.

More Related Videos

Activation and Measurement of NLRP3 Inflammasome Activity Using IL-1β in Human Monocyte-derived Dendritic Cells09:04

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

Published on: May 22, 2014

Myeloid Innate Signaling Pathway Regulation by MALT1 Paracaspase Activity07:09

Myeloid Innate Signaling Pathway Regulation by MALT1 Paracaspase Activity

Published on: January 7, 2019

Related Concept Videos

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...
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...
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...
T Cell Types and Functions01:24

T Cell Types and Functions

When T cells with CD4 markers are activated, they give rise to two types of effector cells: helper T cells and regulatory T cells. Meanwhile, T cells with CD8 markers differentiate into effector cytotoxic T cells. The differentiation of CD4 T cells into helper T cell subsets, such as Th1, Th2, and Th17 cells, is dependent on the antigen type, antigen-presenting cell, and regulatory cytokines.
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...
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...
Phosphoinositides and PIPs01:42

Phosphoinositides and PIPs

Phosphoinositides are a group of phospholipids containing a glycerol backbone with two fatty acid chains and a phosphate attached to a myoinositol sugar ring. The inositol head group extends into the cytoplasm, where it is modified by adding phosphate groups to form phosphatidylinositol phosphates or PIPs.
Different phosphoinositides are synthesized and recruited on the cytosolic face of the plasma membrane. The localization of specific phosphoinositides concentrated in separate membrane...