Constitutive Expression of Human Intercellular Adhesion Molecule-1 (ICAM-1) is Regulated by Differentially Active Enhancing and Silencing Elements

Abstract

While expression of intracellular adhesion molecule 1 (ICAM-1; CD54) is associated with chronic inflammation and autoimmune disease, and is also found on some tumours arising from ICAM-1-negative tissues, in apparently normal tissues it is restricted to a few cell types. Levels of constitutive ICAM-1 expression correlate with the levels of ICAM-1 mRNA. In order to identify regions of the gene regulating its constitutive expression, 5.8 kb of the 5' upstream region was studied in 16 human cell lines using transient transfection of reporter-gene constructs. Three enhancing and one silencing region were observed. While the enhancer upstream of position -1352 was active in all cells investigated, the inhibitory influence of a silencer region between positions -339 and -290 was observed only in 50% of the cells. All cells expressing low levels of ICAM-1, such as may occur in many tissues in vivo, lacked an active silencer. In contrast to the ICAM-1 low-expressing cells, cell lines with high constitutive ICAM-1 levels, as well as those with no ICAM-1 expression, showed an active silencer. Thus, ICAM-1 constitutive expression seems to be regulated in two different ways. The fact that silencer and enhancer activities were observed in both strongly positive and negative ICAM-1 cells, suggests that constitutive ICAM-1 expression is regulated by a balance of enhancing and silencing transcription factors and possible additional elements.