New insights into the regulation of ICAM-1 gene expression

Abstract

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 proinflammatory mediators, interferon-γ and phorbol myristate acetate, and the possible role of the serinekhreonine 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.

Key Words:

• ICAM-1
• mRNA stability
• serine/threonine phosphorylation
• inflammation