Related Experiment Videos

Suppression of vascular permeability and inflammation by targeting of the transcription factor c-Jun

Roger G Fahmy1, Alla Waldman, Guishui Zhang

  • 1Centre for Vascular Research, University of New South Wales, and Department of Haematology, The Prince of Wales Hospital, Sydney NSW 2031, Australia.

Nature Biotechnology
|July 11, 2006
PubMed

Insights

Targeting c-Jun with DNAzyme Dz13 effectively reduces vascular permeability and leukocyte migration. This novel approach shows promise for treating inflammatory diseases like rheumatoid arthritis with fewer side effects.

Area of Science:

  • Molecular Biology
  • Immunology
  • Pharmacology

Background:

  • Conventional anti-inflammatory drugs cause side effects, necessitating targeted therapies.
  • Vascular permeability and leukocyte emigration are key processes in inflammation.

Purpose of the Study:

  • To investigate the efficacy of DNAzyme Dz13 in suppressing inflammation by targeting c-Jun.
  • To evaluate Dz13 as a novel therapeutic agent for inflammatory conditions.

Main Methods:

  • Utilized murine models for vascular permeability, inflammation, acute inflammation, and rheumatoid arthritis.
  • Administered Dz13 to assess its impact on vascular permeability, leukocyte adhesion, and infiltration.
  • Conducted mechanistic studies to identify molecular targets of Dz13.

Main Results:

  • Dz13 significantly reduced vascular permeability induced by anaphylactic challenge or VEGF.
  • Dz13 inhibited leukocyte rolling, adhesion, and extravasation in inflammatory models.
  • Dz13 suppressed neutrophil infiltration and attenuated joint swelling and bone erosion in rheumatoid arthritis models.

Conclusions:

  • Targeting c-Jun with Dz13 is a viable strategy for developing novel anti-inflammatory therapies.
  • Dz13 effectively blocks key inflammatory pathways, including endothelial adhesion molecule expression.

Related Concept Videos

Eukaryotic Transcription Inhibitors01:52

Eukaryotic Transcription Inhibitors

Certain biochemical processes, such as embryonic development and cell growth regulation, depend on the repression of specific genes. DNA binding proteins known as eukaryotic transcription inhibitors regulate the repression of gene expression in eukaryotes. The presence of these inhibitors at the required location and time in the cell is triggered by the presence of hormones and additional signals from other cells.
Eukaryotic transcription inhibitors usually contain two distinct domains, a DNA...
Inflammatory Response01:28

Inflammatory Response

An inflammatory response is a localized, nonspecific immune reaction that occurs when a tissue is injured. It is characterized by redness, swelling, heat, and pain, which are commonly called the cardinal signs and symptoms of inflammation. Inflammation can sometimes result in a loss of function.
Inflammation can be triggered by various stimuli, such as impact, abrasion, chemical irritation, infections, and extreme hot or cold temperatures. These can damage cells and connective tissue fibers,...
Regulation of Angiogenesis and Blood Supply01:24

Regulation of Angiogenesis and Blood Supply

Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits.  Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl hydroxylase and factor...
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...
Master Transcription Regulators02:23

Master Transcription Regulators

Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a  complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...