Colchicine and griseofulvin inhibit VCAM-1 expression on human vascular endothelial cells - evidence for the association of VCAM-1 expression with microtubules

We have previously reported that griseofulvin inhibits VCAM-1 expression on human vascular endothelial cells. Since griseofulvin interferes with microtubule assembly, we used colchicine as another microtubule antagonist and compared it with griseofulvin to further characterize this inhibition. By flow cytometry, colchicine inhibited VCAM-1 induction on TNF alpha -stimulated human dermal microvascular endothelial cells (HDMEC) dose-dependently. Colchicine also inhibited VCAM-1 induction on both TNF alpha- and IL-1 alpha -stimulated human umbilical vein endothelial cells (HUVEC). Although this inhibition was reversible, colchicine-treated cells showed slower restoration of its expression than griscofulvin-treated cells. Moreover, co-incubation with a microtubule stabilizer paclitaxel blocked this inhibition, and colchicine-treated cells were more resistant to this blocking than griseofulvin. RT-PCR of HDMEC showed inhibition of the transcript level of VCAM-1 by both antagonists. These results indicate intimate association between VCAM-1 expression and microtubules. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.