Pyrrolidine dithiocarbamate inhibits cytokine-induced VCAM-1 gene expression in rat cardiac myocytes.
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.
Hattori
Y
Y
Department of Endocrinology, Dokkyo University School of Medicine, Tochigi, Japan.
Akimoto
K
K
Murakami
Y
Y
Kasai
K
K
D000818:Animals; D002478:Cells, Cultured; D007375:Interleukin-1 / Q000037:antagonists & inhibitors*; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D016328:NF-kappa B / Q000037:antagonists & inhibitors; D011759:Pyrrolidines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013859:Thiocarbamates / Q000494:pharmacology*; D019010:Vascular Cell Adhesion Molecule-1 / Q000032:analysis / Q000187:drug effects* / Q000235:genetics*
D007375:Interleukin-1; D016328:NF-kappa B; D011759:Pyrrolidines; D013859:Thiocarbamates; D019010:Vascular Cell Adhesion Molecule-1; C020972:pyrrolidine dithiocarbamic acid