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 micro tubule assembly, we used colchicine as another microtubule antagonist and c ompared it with griseofulvin to further characterize this inhibition. By fl ow cytometry, colchicine inhibited VCAM-1 induction on TNF alpha -stimulate d human dermal microvascular endothelial cells (HDMEC) dose-dependently. Co lchicine also inhibited VCAM-1 induction on both TNF alpha- and IL-1 alpha -stimulated human umbilical vein endothelial cells (HUVEC). Although this i nhibition was reversible, colchicine-treated cells showed slower restoratio n of its expression than griscofulvin-treated cells. Moreover, co-incubatio n with a microtubule stabilizer paclitaxel blocked this inhibition, and col chicine-treated cells were more resistant to this blocking than griseofulvi n. RT-PCR of HDMEC showed inhibition of the transcript level of VCAM-1 by b oth antagonists. These results indicate intimate association between VCAM-1 expression and microtubules. (C) 2001 Elsevier Science Ireland Ltd. All ri ghts reserved.