Regulation of intercellular adhesion molecule-1 (CD54) gene expression

Intercellular adhesion molecule-1 (ICAM-1, CD54) is an inducible cell adhes ion glycoprotein of the immunoglobulin supergene family expressed on the su rface of a wide variety of cell types. ICAM-1 interactions with the Beta(2) integrins CD11a/CD18 (LFA-1) and CD11b/CD18 (MAC-1) on the surface of leuk ocytes are important for their transendothelial migration to sites of infla mmation and their function as costimulatory molecules for T cell activation . ICAM-1 is constitutively expressed on the cell surface and is up-regulate d in response to a variety of inflammatory mediators, including proinflamma tory cytokines, hormones, cellular stresses, and virus infection. These sti muli increase ICAM-1 expression primarily through activation of ICAM-1 gene transcription. During the past decade much has been learned about the cell type- and stimulus-specific transcription of ICAM-1. The architecture of t he ICAM-1 promoter is complex, containing a large number of binding sites f or inducible transcription factors, the most important of which is nuclear factor-kappa B (NF-kappaB). NF-kappaB acts in concert with other transcript ion factors and co-activators via specific protein-protein interactions, wh ich facilitate the assembly of distinct stereo-specific transcription compl exes on the ICAM-1 promoter. These transcription complexes presumably media te the induction of ICAM-1 expression in different cell types and in respon se to different stimuli. In this review, we summarize our current understan ding of ICAM-1 gene regulation with a particular emphasis on the transcript ions factors and signal transduction pathways critical for the cell type- a nd stimulus-specific activation of ICAM-1 gene transcription. J.Leukoc. Bio l. 66: 876-888; 1999.