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 TNFalpha-stimulated human dermal microvascular endothelial cells (HDMEC) dose-dependently. Colchicine also inhibited VCAM-1 induction on both TNFalpha- and IL-1alpha-stimulated human umbilical vein endothelial cells (HUVEC). Although this inhibition was reversible, colchicine-treated cells showed slower restoration of its expression than griseofulvin-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.
Asahina
A
A
Department of Dermatology, Faculty of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, 113-8655, Tokyo, Japan.
Tada
Y
Y
Nakamura
K
K
Tamaki
K
K
D002478:Cells, Cultured; D003078:Colchicine / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D006118:Griseofulvin / Q000494:pharmacology*; D006801:Humans; D008870:Microtubules / Q000187:drug effects / Q000378:metabolism; D017239:Paclitaxel / Q000494:pharmacology; D014158:Transcription, Genetic / Q000187:drug effects; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism*
D019010:Vascular Cell Adhesion Molecule-1; D006118:Griseofulvin; D017239:Paclitaxel; D003078:Colchicine