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, LPS, IFN-gamma), which are released during the inflammatory process. We have investigated the possibility that other factors, related to the stress 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 ICAM-1 gene expression shows a maximum level of induction 4 h after 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 increase in RNA expression seems significantly greater that the subsequent 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. may be linked to the cellular specificity.
Martinotti
S
S
Department of Experimental Medicine, University of L'Aquila, Italy.
Toniato
E
E
Colagrande
A
A
Alesse
E
E
Alleva
C
C
Screpanti
I
I
Morrone
S
S
Scarpa
S
S
Frati
L
L
Hayday
A C
AC
D002104:Cadmium / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis* / Q000235:genetics; D016131:Lymphocyte Subsets / Q000187:drug effects / Q000378:metabolism; D009928:Organ Specificity; D014158:Transcription, Genetic / Q000187:drug effects; D015032:Zinc / Q000494:pharmacology*
D002104:Cadmium; D018799:Intercellular Adhesion Molecule-1; D015032:Zinc