Kazumi Hayashi (1), Tadashi Nagamatsu (1), Mikio Ito (1), Hideo Yagita (2) and Yoshio Suzuki (1, *)
(1) Department of Pharmacology, Faculty of Pharmacy, Meijo University, 150 Yagotoyama, Tenpaku-ku, Nagoya 468, Japan (2) Department of Immunology, Juntendo University School of Medicine, Hongo 2-1-1, Bunkyo-ku, Tokyo 113, Japan
(*) To whom correspondence should be addressed.
Abstract: It is known that adhesion molecules play a crucial role in the development of glomerulo-nephritis. Therefore, we investigated the effects of acteoside on the expression of intercellular adhesion molecule-1 (ICAM-1) in nephritic glomeruli, in vivo, and human umbilical vein endothelial cells (HUVECs) and rat mesangial cells, in vitro. Acteoside treatment significantly decreased the up-regulation of ICAM-1 expression in nephritic glomeruli. Acteoside prevented the up-regulation of ICAM-1 expression mediated by inflammatory cytokines or phorbol 12-myristate 13-acetate on HUVECs and rat mesangial cells. Adhesion of neutrophils and macrophages to acteoside-treated HUVECs was suppressed to one half of that in untreated HUVECs. These data support the finding that acteoside inhibits the up-regulation of ICAM-1 in the nephritic glomeruli. Additionally, it is suggested that the antinephritic action of acteoside is due to the inhibition of intraglomerular accumulation of leukocytes through the prevention of the up-regulation of ICAM-1. This is the first paper demonstrating that the up-regulation of ICAM-1 in nephritic glomeruli is inhibited by a natural product, acteoside.
Keywords:
Acteoside, Anti-GBM nephritis, Adhesion molecule, Neutrophil, Endothelial cell