Pharmacological modulation of endothelial cell-associated adhesion molecule expression: implications for future treatment of dermatological diseases.
Skin diseases with an inflammatory component, regardless of their etiology, are characterized at some point by the extravasation and subsequent infiltration of leukocytes into the dermal and/or epidermal compartments. This trafficking pattern is determined by a complex series of events whereby the leukocytes interact with cell adhesion molecules (CAM), particularly those induced on endothelial cells following activation with various inflammatory mediators. Vascular CAMs belonging to the selectin family (i.e., P-selectin and E-selectin) are thought to mediate early and reversible events involving leukocyte rolling and margination along the lumenal surface of microvascular cells (post-capillary venules). Certain members of the immunoglobulin supergene family (i.e., VCAM-1 and ICAM-1) regulate later and irreversible steps which lead to firm attachment and subsequent diapedesis of leukocytes. Accumulating evidence suggests that if one blocks the ligand-binding sites between leukocytes and endothelial cells, or inhibits vascular CAM expression, hematopoietic cell extravasation and progressive inflammatory events can be greatly diminished. To identify such inhibitors we developed a cell-based Elisa using the human microvascular cell line HMEC-1. As reported in the present paper, this approach yielded a naturally-occurring, low molecular weight compound which potently inhibits cytokine-induced adhesion molecule expression on cultured endothelial cells, without modulating "house-keeping" proteins.
Foster
C A
CA
Department of Dermatology, Sandoz Research Institute, Vienna, Austria.
Dreyfuss
M
M
Mandak
B
B
Meingassner
J G
JG
Naegeli
H U
HU
Nussbaumer
A
A
Oberer
L
L
Scheel
G
G
Swoboda
E M
EM
D015815:Cell Adhesion Molecules / Q000096:biosynthesis / Q000187:drug effects*; D002460:Cell Line; D016572:Cyclosporine / Q000494:pharmacology; D016207:Cytokines / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D005938:Glucocorticoids / Q000494:pharmacology; D006801:Humans; D007962:Leukocytes / Q000187:drug effects / Q000378:metabolism; D016559:Tacrolimus / Q000494:pharmacology
D015815:Cell Adhesion Molecules; D016207:Cytokines; D005938:Glucocorticoids; D016572:Cyclosporine; D016559:Tacrolimus