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Constitutive expression of human intercellular adhesion molecule-1 (ICAM-1) is regulated by differentially active

A Jahnke1, A Van de Stolpe, E Caldenhoven

  • 1Institute of Immunology, Munich, Germany.

European Journal of Biochemistry
|March 1, 1995
PubMed

Insights

Intracellular adhesion molecule 1 (ICAM-1) gene expression is regulated by both enhancers and silencers. This balance determines ICAM-1 levels in different cell types, impacting inflammation and autoimmune disease.

Area of Science:

  • Molecular biology
  • Immunology
  • Genetics

Background:

  • Intracellular adhesion molecule 1 (ICAM-1; CD54) expression is linked to chronic inflammation, autoimmune diseases, and certain tumors.
  • In normal tissues, ICAM-1 is constitutively expressed at low levels in specific cell types.
  • Constitutive ICAM-1 expression levels correlate with ICAM-1 mRNA levels.

Purpose of the Study:

  • To identify regulatory regions within the 5' upstream region of the ICAM-1 gene responsible for its constitutive expression.
  • To understand the mechanisms controlling basal ICAM-1 gene transcription in human cell lines.

Main Methods:

  • Analysis of 5.8 kb of the ICAM-1 5' upstream region using transient transfection of reporter-gene constructs in 16 human cell lines.
  • Investigated enhancer and silencer activities within the promoter region.

Main Results:

  • Identified three enhancer regions and one silencer region within the ICAM-1 5' upstream sequence.
  • An enhancer upstream of -1352 was active in all tested cell lines.
  • A silencer region (-339 to -290) was active in only 50% of cell lines, particularly those with high or no ICAM-1 expression, but absent in low-expressing cells.

Conclusions:

  • Constitutive ICAM-1 expression appears to be regulated by a dual mechanism involving both enhancing and silencing elements.
  • The balance between these regulatory elements, influenced by transcription factors, dictates ICAM-1 expression levels.
  • Differential activity of the silencer region may explain variations in ICAM-1 expression across different cell types in vivo.

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