New insights into the regulation of ICAM-1 gene expression.
Cell-cell adhesion is critical in the generation of effective immune responses and is dependent upon the expression of a variety of cell surface receptors. Intercellular adhesion molecule-1 (ICAM-1; CD54) is an inducible cell surface glycoprotein expressed at a low level on a subpopulation of hematopoietic cells, vascular endothelium, fibroblasts, and certain epithelial cells. However, its expression is dramatically increased at sites of inflammation, providing important means of regulating cell-cell interactions and thereby inflammatory responses. Inasmuch the modulation of ICAM-1 expression during inflammation by pharmacologic agents might be very attractive for medical treatment, the intracellular regulatory elements and signaling pathways underlying the inducible expression of ICAM-1 by proinflammatory cytokines remain largely unknown. In this review, a novel posttranscriptional regulation of ICAM-1 gene expression by two inflammatory mediators, interferon-gamma and phorbol myristate acetate, and the possible role of the serine/threonine phosphorylation pathway in the cycloheximide-induced ICAM-1 message stabilization are discussed in light of our current understanding of ICAM-1 gene regulation during an inflammatory response.
Ohh
M
M
Department of Medical Genetics, University of British Columbia, Vancouver, Canada.
Takei
F
F
D000818:Animals; D015703:Antigens, CD / Q000235:genetics; D001665:Binding Sites; D015815:Cell Adhesion Molecules / Q000235:genetics; D003513:Cycloheximide / Q000494:pharmacology; D005786:Gene Expression Regulation; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics*; D007371:Interferon-gamma / Q000502:physiology*; D010768:Phosphoserine / Q000378:metabolism; D010769:Phosphothreonine / Q000378:metabolism; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics; D012045:Regulatory Sequences, Nucleic Acid; D017384:Sequence Deletion; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D014158:Transcription, Genetic / Q000187:drug effects
D015703:Antigens, CD; D015815:Cell Adhesion Molecules; C065289:ICAM2 protein, human; D011500:Protein Synthesis Inhibitors; D012333:RNA, Messenger; D010769:Phosphothreonine; D018799:Intercellular Adhesion Molecule-1; D010768:Phosphoserine; D007371:Interferon-gamma; D003513:Cycloheximide; D013755:Tetradecanoylphorbol Acetate