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 therefore investigated its putative immunomodulatory roles by flow cytometric analysis of cell adhesion molecules on human leukocytes and human vascular endothelial cells. Griseofulvin downregulated L-selectin expression on neutrophils, but not on lymphocytes, in a dose-dependent manner. Griseofulvin did not affect CD11b/CD18 expression on neutrophils. On human dermal microvascular endothelial cells (HDMEC), griseofulvin inhibited the expression of TNF alpha-induced VCAM-1 dose-dependently, and this inhibition was fully reversible. Similarly, griseofulvin inhibited the induction of VCAM-1 expression on both TNF alpha- and IL-1 alpha-stimulated human umbilical vein endothelial cells (HUVEC). In addition, it partially inhibited the induction of E-selectin expression, whereas it had a marginal effect on ICAM-1 expression. Reverse transcription-polymerase chain reaction of TNF alpha-stimulated 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.
Asahina
A
A
Department of Dermatology, The University of Tokyo School of Medicine, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.
Tada
Y
Y
Nakamura
K
K
Tamaki
K
K
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000935:Antifungal Agents / Q000494:pharmacology; D001483:Base Sequence; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D017931:DNA Primers / Q000235:genetics; D019040:E-Selectin / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D006118:Griseofulvin / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D019041:L-Selectin / Q000378:metabolism; D007962:Leukocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism
D000276:Adjuvants, Immunologic; D000935:Antifungal Agents; D015815:Cell Adhesion Molecules; D017931:DNA Primers; D019040:E-Selectin; D012333:RNA, Messenger; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D019041:L-Selectin; D006118:Griseofulvin