Daunorubicin inhibits gene expression of cyclooxygenase-2 in vascular smooth muscle cells

Daunorubicin (0-1-1 muM) concentration-dependently inhibited prostacyclin production induced by interleukin-1 beta (IL-1 beta, 2.5 ng/ml) in cultured aortic smooth muscle cells isolated from rats. IL10 stimulation caused activation of nuclear factor-kappaB (NF-kappaB) and expression of cyclooxygenase-2 (COX-2) mRNA and protein, which were inhibited by daunorubicin. However, COX activity, evaluated by conversion of exogenous arachidonic acid to prostacyclin, was not affected by daunorubicin (0.1-1 muM). Protein expression of COX-1 and NF-kappaB was not affected by daunorubicin. Daunorubicin also inhibited nitric oxide (NO) production induced by IL-1 beta. These results suggest that daunorubicin attenuated prostacyclm* synthesis through inhibiting expression of COX-2 mRNA, which could be explained by perturbation of NF-kappaB activation. (C) 2001 Elsevier Science Ltd. All rights reserved.