HEAVY-METAL MODULATION OF THE HUMAN INTERCELLULAR-ADHESION MOLECULE (ICAM-1) GENE-EXPRESSION

The intercellular adhesion molecule 1 (ICAM-1) can be induced on many different cell types by a set of various modulators (IL1 beta, TNF, LP S, IFN-gamma), which are released during the inflammatory process. We have investigated the possibility that other factors, related to the s tress and biophysical perturbations of the inflammatory response, may also modulate ICAM-1. Here, we report that heavy metals, in particular zinc, can enhance the expression of the ICAM-1 gene on cells actively involved at different levels during inflammation. Kinetic studies of the ICAM-1 gene expression shows a maximum level of induction 4 h afte r treatment with metals, followed by a rapid decrease to basal levels within 12 h. The effect on enhanced gene expression is mostly due to a rapid increase of the transcriptional rate as shown by nuclear run-on experiments. In B lymphoblastoid cells, but not in fibroblasts, the i ncrease in RNA expression seems significantly greater that the subsequ ent increase in protein expression, suggesting that a further point of post-transcriptional regulation of ICAM-1 occurs and may be linked to the cellular specificity.