Griseofulvin has a potential to modulate the expression of cell adhesion molecules on leukocytes and vascular endothelial cells

Griseofulvin has been used as an antifungal drug for many years, but it has recently been shown effective for several inflammatory skin diseases. We t herefore investigated its putative immunomodulatory roles by flow cytometri c analysis of cell adhesion molecules on human leukocytes and human vascula r endothelial cells. Griseofulvin downregulated L-selectin expression on ne utrophils, but not on lymphocytes, in a dose-dependent manner. Griseofulvin did not affect CD11b/CD18 expression on neutrophils. On human dermal micro vascular endothelial cells (HDMEC), griseofulvin inhibited the expression o f TNF alpha -induced VCAM-1 dose-dependently, and this inhibition was fully reversible. Similarly, griseofulvin inhibited the induction of VCAM-1 expr ession on both TNF alpha- and IL-1 alpha -stimulated human umbilical vein e ndothelial cells (HUVEC), In addition, it partially inhibited the induction of E-selectin expression, whereas it had a marginal effect on ICAM-1 expre ssion. Reverse transcription-polymerase chain reaction of TNF alpha -stimul ated HDMEC showed inhibition of VCAM-1, but not ICAM-1 gene transcription. These results indicate potent immunomodulatory properties of griseofulvin, which may be associated with its feature as a microtubule antagonist. (C) 2 001 Elsevier Science B.V. All rights reserved.