Pyrrolidine dithiocarbamate inhibits cytokine-induced VCAM-1 gene expression in rat cardiac myocytes.

Abstract

We investigated whether interleukin-1alpha (IL-1) would induce gene expression of vascular cell adhesion molecule-1 (VCAM-1) in cardiac myocytes and, if so, whether nuclear factor kappaB (NF-kappaB) was involved. We evaluated the VCAM-1 gene expression in cultured neonatal rat cardiac myocytes by the reverse transcription-polymerase chain reaction. IL-1 alone or together with interferon-gamma (IFN) induced VCAM-1 gene expression in the cells. Induction of VCAM-1 gene expression in response to IL-1 and IFN was antagonized in a concentration-dependent manner by pyrrolidine dithiocarbamate, an inhibitor of NF-kappa b activation (25-100 microM). Tosyl-lysine-chloromethyl ketone, another inhibitor of NF-kappa b activation, also inhibited the expression of the VCAM-1 gene in response to IL-1 and IFN. Thus, VCAM-1 gene expression appeared to be mediated by NF-kappa b in cardiac myocytes, and this cardiac myocyte VCAM-1 may be involved in cardiac inflammatory disorders. Disruption of expression of VCAM-1 by inhibition of NF-kappa b activation may indicate a target for pharmacologic intervention intended to limit cardiac inflammation.