Related Experiment Video

Updated: Jul 10, 2026

A High Resolution Method to Monitor Phosphorylation-dependent Activation of IRF3
11:44

A High Resolution Method to Monitor Phosphorylation-dependent Activation of IRF3

Published on: January 24, 2016

The interferon-stimulated gene factor 3 complex mediates the inhibitory effect of interferon-beta on matrix

Xueyan Zhao1, Susan Nozell, Zhendong Ma

  • 1Department of Cell Biology, University of Alabama at Birmingham, AL 53294-0005, USA.

The FEBS Journal
|November 22, 2007
PubMed

Insights

Interferon-beta suppresses matrix metalloproteinase-9 (MMP-9) gene expression transcriptionally. This requires the interferon-stimulated gene factor 3 (ISGF3) complex, impacting inflammatory diseases and cancer progression.

Area of Science:

  • Molecular Biology
  • Immunology
  • Biochemistry

Background:

  • Matrix metalloproteinase-9 (MMP-9) is crucial in physiological and pathological processes, including inflammation and cancer.
  • Interferon-beta (IFN-β) is a cytokine with diverse biological activities, primarily known for positive gene regulation via the JAK-STAT pathway.

Purpose of the Study:

  • To elucidate the mechanisms by which interferon-beta negatively regulates gene expression, specifically focusing on MMP-9.
  • To determine the role of the interferon-stimulated gene factor 3 (ISGF3) complex in IFN-β-mediated MMP-9 suppression.

Main Methods:

  • Utilized cell lines deficient in STAT-1, STAT-2, and interferon regulatory factor 9 (IRF9) to assess ISGF3 complex involvement.
  • Performed chromatin immunoprecipitation (ChIP) assays to analyze protein recruitment to the MMP-9 promoter.
  • Assessed histone acetylation levels at the MMP-9 promoter.

Main Results:

  • Interferon-beta significantly inhibits MMP-9 gene expression at the transcriptional level.
  • All three components of the ISGF3 complex (STAT-1, STAT-2, IRF9) are essential for IFN-β-induced MMP-9 suppression.
  • IFN-β reduces the recruitment of key transcriptional activators (NF-κB p65, Sp1) and coactivators (CBP, p300) to the MMP-9 promoter.
  • IFN-β decreases histone acetylation at the MMP-9 promoter, independent of direct ISGF3 binding.

Conclusions:

  • Interferon-beta actively suppresses MMP-9 gene expression through transcriptional mechanisms.
  • The ISGF3 complex plays a critical role in mediating IFN-β's inhibitory effect on MMP-9.
  • These findings reveal novel insights into IFN-β's regulatory functions and its potential as a therapeutic target in MMP-9-driven diseases.

More Related Videos

High-throughput Quantitative Real-time RT-PCR Assay for Determining Expression Profiles of Types I and III Interferon Subtypes10:00

High-throughput Quantitative Real-time RT-PCR Assay for Determining Expression Profiles of Types I and III Interferon Subtypes

Published on: March 24, 2015

Vasodilation of Isolated Vessels and the Isolation of the Extracellular Matrix of Tight-skin Mice08:09

Vasodilation of Isolated Vessels and the Isolation of the Extracellular Matrix of Tight-skin Mice

Published on: March 24, 2017

Related Concept Videos

Inhibitors of Viral Protein Synthesis01:30

Inhibitors of Viral Protein Synthesis

Protein synthesis is indispensable for viral replication, as viruses lack the cellular machinery required for this process and must hijack the host's translational apparatus. In response, host cells deploy a critical innate immune defense involving interferons, specialized cytokines that play a central role in inhibiting viral propagation.Upon viral detection, infected cells release interferons that bind to receptors on adjacent uninfected cells, activating the JAK-STAT signaling pathway and...
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...
Role of Matrix Metalloproteases in Degradation of ECM01:23

Role of Matrix Metalloproteases in Degradation of ECM

Matrix metalloproteases (MMPs) are enzymes involved in the hydrolysis of proteins and glycoproteins of the extracellular matrix. MMPs are essential for the migration and proliferation of cells through the dense matrix network, throughout embryonic development, and throughout morphogenesis. The first MMP activity discovered was a collagenase in a tadpole's tail undergoing metamorphosis. The active collagen deposition and modifications lead to the morphogenesis of tadpoles into the adult body.
A...
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...
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...