Related Experiment Video

Updated: Aug 15, 2026

Analysis of Schwann-astrocyte Interactions Using In Vitro Assays
10:17

Analysis of Schwann-astrocyte Interactions Using In Vitro Assays

Published on: January 14, 2011

Transcriptional regulation of intercellular adhesion molecule-1 in astrocytes involves NF-kappaB and C/EBP isoforms

S J Lee1, J Hou, E N Benveniste

  • 1Department of Cell Biology, University of Alabama at Birmingham 35294-0005, USA.

Journal of Neuroimmunology
|January 23, 1999
PubMed

Insights

Cytokine-induced ICAM-1 expression in astrocytes involves NF-kappaB and C/EBP transcription factors. These factors interact to regulate ICAM-1 gene transcription in the central nervous system.

Area of Science:

  • Neuroimmunology
  • Molecular Biology
  • Cellular Biology

Background:

  • Intercellular Adhesion Molecule-1 (ICAM-1) is crucial for immune cell trafficking and responses in inflamed tissues.
  • Astrocytes, immune effector cells in the central nervous system (CNS), upregulate ICAM-1 in response to proinflammatory cytokines like TNF-alpha and IL-1beta.

Purpose of the Study:

  • To elucidate the transcriptional regulatory mechanisms of ICAM-1 in astrocytes stimulated by TNF-alpha and IL-1beta.
  • To identify the specific transcription factors and their binding sites involved in ICAM-1 gene upregulation.

Main Methods:

  • Utilized human ICAM-1 promoter-luciferase reporter constructs transfected into astrocytes.
  • Stimulated astrocytes with TNF-alpha and IL-1beta to assess promoter activity.
  • Performed electrophoretic mobility shift assays (EMSA) to identify transcription factor binding.

Main Results:

  • Identified critical binding sites for NF-kappaB (at -186 bp) and C/EBP (at -198 bp) in the ICAM-1 promoter.
  • Demonstrated that p65 homodimers and p65/p50 heterodimers bind to the NF-kappaB site, while C/EBPdelta homodimers and C/EBPbeta/delta heterodimers bind to the C/EBP site.
  • Showed that p65 transactivates ICAM-1 promoter activity, p50 inhibits p65-mediated transcription, and C/EBPbeta can abolish p65's transactivating effects.

Conclusions:

  • Cytokine-induced ICAM-1 expression in astrocytes is regulated by the interplay between NF-kappaB and C/EBP transcription factors.
  • Specific isoforms of NF-kappaB and C/EBP proteins bind to distinct promoter regions, influencing ICAM-1 transcription.
  • The findings provide insights into the molecular mechanisms controlling immune cell interactions within the CNS.

More Related Videos

Methods for the Modulation and Analysis of NF-κB-dependent Adult Neurogenesis14:58

Methods for the Modulation and Analysis of NF-κB-dependent Adult Neurogenesis

Published on: February 14, 2014

Correlating Gene-specific DNA Methylation Changes with Expression and Transcriptional Activity of Astrocytic KCNJ10 (Kir4.1)11:19

Correlating Gene-specific DNA Methylation Changes with Expression and Transcriptional Activity of Astrocytic KCNJ10 (Kir4.1)

Published on: September 26, 2015

Related Concept Videos

Regulation of Nuclear Protein Sorting01:45

Regulation of Nuclear Protein Sorting

Nuclear protein sorting regulates nucleus composition and gene expression, crucial for determining the fate of a eukaryotic cell. Hence, the entry and exit of molecules across the nuclear envelope is a tightly controlled process. Nuclear protein sorting can be inhibited by one of the following ways: 1) masking cargo signal sequences, 2) modifying the nuclear receptor's affinity for cargo, 3) controlling the nuclear pore size, 4) retaining the cargo during its transit to the cytosol or the...
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...
Overview of Cell-Matrix Interactions01:24

Overview of Cell-Matrix Interactions

The extracellular matrix or ECM holds cells together to form a tissue and allows the cells within the tissue to communicate. ECM comprises proteins such as fibronectin, collagen, laminin, etc. The most abundant protein in this space is collagen. Collagen fibers are interwoven with carbohydrate-containing protein molecules called proteoglycans. ECM allows cell migration and provides a structural scaffold at cell adhesion that anchors the cell when the extracellular matrix proteins interact with...
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...
Cell Adhesion Molecules - Types and Functions01:20

Cell Adhesion Molecules - Types and Functions

Cell adhesion molecules (CAMs) are pivotal to multicellularity and the coordinated functioning of tissues and organ systems. They enable physical interactions between cells and provide mechanical strength to tissues. They also function as receptors for signal transmission across the plasma membrane. The CAMs are broadly classified into four families - integrins, cadherins, selectins, and immunoglobulin-like CAMs (IgCAMs).
CAM Families
The Integrin family of proteins is primarily  involved in a...
Immunoglobulin-like Cell Adhesion Molecules01:31

Immunoglobulin-like Cell Adhesion Molecules

Immunoglobulin-like cell adhesion molecules or Ig-CAMs are a versatile group of cell surface glycoproteins belonging to the immunoglobulin protein superfamily. Ig-CAMs possess the characteristic immunoglobulin protein domains and other domains such as the fibronectin type III domain. The Ig domains are glycosylated to varying degrees in different Ig-CAMs.
Ig-CAMs exhibit either homophilic binding (to other Ig-CAMs) or heterophilic binding (to other ligands such as integrins). While most Ig-CAMs...