Related Experiment Videos

The toll-like receptor-nuclear factor kappaB pathway in rheumatoid arthritis

Evangelos Andreakos1, Sandra Sacre, Brian M Foxwell

  • 1Kennedy Institute of Rheumatology Division, Faculty of Medicine, Imperial College of Science, Technology and Medicine, London, United Kingdom. evangelos.andreakos@imperial.ac.uk

Frontiers in Bioscience : a Journal and Virtual Library
|June 23, 2005
PubMed

Insights

Nuclear Factor kappaB (NF-kappaB) drives inflammation and joint damage in rheumatoid arthritis (RA). Targeting the Toll-like receptor (TLR)-NF-kappaB pathway offers new therapeutic strategies for RA, but must match anti-TNF agent efficacy and safety.

Area of Science:

  • Immunology
  • Rheumatology
  • Molecular Biology

Background:

  • Cytokines like TNF are key targets in rheumatoid arthritis (RA) treatment, with anti-TNF therapies setting a high standard.
  • Despite successful cytokine targeting, the triggers for inflammatory cytokine production in RA remain unclear.
  • Nuclear Factor kappaB (NF-kappaB) is implicated in expressing inflammatory cytokines and tissue-degrading enzymes in RA.

Purpose of the Study:

  • To review evidence on the role of NF-kappaB in RA pathogenesis.
  • To explore the involvement of Toll-like receptors (TLRs) in initiating RA inflammation and joint destruction.
  • To assess the potential of targeting the TLR-NF-kappaB pathway for RA therapeutics.

Main Methods:

  • Review of existing scientific literature and evidence regarding cytokine signaling in RA.
  • Analysis of the NF-kappaB pathway's role in the expression of inflammatory mediators and enzymes.
  • Evaluation of TLRs as potential therapeutic targets in RA treatment strategies.

Main Results:

  • NF-kappaB is essential for the expression of inflammatory cytokines and tissue-degrading enzymes in RA.
  • TLRs, as activators of NF-kappaB, are potentially involved in triggering RA's inflammatory and destructive processes.
  • The TLR-NF-kappaB pathway presents significant opportunities for therapeutic intervention in RA.

Conclusions:

  • The TLR-NF-kappaB pathway is a promising target for novel RA therapies.
  • Future RA drugs targeting this pathway must demonstrate comparable or superior efficacy and safety to current anti-TNF agents.
  • Predicting the safety profile of new therapeutic interventions remains a significant challenge.

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...
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...
TGF - β Signaling Pathway01:16

TGF - β Signaling Pathway

The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors are of three kinds RI, RII, and RIII. The RI...
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...
NF-kB-dependent Signaling Pathway02:26

NF-kB-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...