Sodium arsenite-induced inhibition of cell proliferation is related to inhibition of IL-2 mRNA expression in mouse activated T cells.

Autor: Conde P; Sección Toxicología, Centro de Investigación y de Estudios Avanzados, CINVESTAV, P.O. Box 14-740, Mexico, D.F., 07360, Mexico., Acosta-Saavedra LC, Goytia-Acevedo RC, Calderon-Aranda ES
Jazyk: angličtina
Zdroj: Archives of toxicology [Arch Toxicol] 2007 Apr; Vol. 81 (4), pp. 251-9. Date of Electronic Publication: 2006 Sep 29.
DOI: 10.1007/s00204-006-0152-7
Abstrakt: A proposed mechanism for the As-induced inhibition of cell proliferation is the inhibition of IL-2 secretion. However, the effects of arsenite on IL-2 mRNA expression or on the ERK pathway in activated-T cells have not yet been described. We examined the effect of arsenite on IL-2 mRNA expression, cell activation and proliferation in PHA-stimulated murine lymphocytes. Arsenite (1 and 10 microM) decreased IL-2 mRNA expression, IL-2 secretion and cell proliferation. Arsenite (10 microM) strongly inhibited ERK-phosphorylation. However, the partial inhibition (50%) of IL-2 mRNA produced by 1 microM, consistent with the effects on IL-2 secretion and cell proliferation, could not be explained by the inhibition of ERK-phosphorylation, which was not affected at this concentration. The inhibition of IL-2 mRNA expression caused by 1 microM could be associated to effects on pathways located downstream or parallel to ERK. Arsenite also decreased early activation (surface CD69+ expression) in both CD4+ and CD8+, and decreased total CD8+ count without significantly affecting CD4+, supporting that the cellular immune response mediated by cytotoxic T cells is an arsenic target. Thus, our results suggest that arsenite decreases IL-2 mRNA levels and T-cell activation and proliferation. However, further studies on the effects of arsenite on IL-2 gene transcription and IL-2 mRNA stability are needed.
Databáze: MEDLINE
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