Ganoderma lucidum polysaccharides attenuate endotoxin-induced intercellular cell adhesion molecule-1 expression in cultured smooth muscle cells and in the neointima in mice.
The expression of adhesion molecules on vessels and subsequent leukocyte recruitment are critical events in vascular diseases and inflammation. The aim of the present study was to examine the effects of an extract of Ganoderma lucidum (Reishi) polysaccharides (EORP), which is effective against cancer and immunological disorders, on adhesion molecule expression by human aortic smooth muscle cells (HASMCs) and the underlying mechanism. EORP significantly suppressed lipopolysaccharide (LPS)-induced intercellular cell adhesion molecule-1 (ICAM-1) mRNA and protein expression and reduced the binding of human monocytes to LPS-stimulated HASMCs. Immunoprecipitation and real-time polymerase chain reaction demonstrated that EORP markedly reduced the interaction of human antigen R protein (HuR) with the 3'-UTR of ICAM-1 mRNA in LPS-stimulated HASMCs. EORP treatment also suppressed extracellular signal-regulated kinase (ERK) phosphorylation and reduced the density of the shifted bands of nuclear factor (NF)-kappaB after LPS-induced activation. In an endothelial-denuded artery model in LPS-treated mice, daily oral administration of EORP for 2 weeks decreased neointimal hyperplasia and ICAM-1 expression in the plasma and neointima. These results provide evidence that EORP attenuates LPS-induced adhesion molecule expression and monocyte adherence and that this protective effect is mediated by decreased ERK phosphorylation and NF-kappaB activation. These findings suggest that EORP has anti-inflammatory properties and could prove useful in the prevention of vascular diseases and inflammatory responses.
Lin
Ching-Yuang
CY
Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan.
Chen
Yung-Hsiang
YH
Lin
Chia-Ying
CY
Hsu
Hsien-Yeh
HY
Wang
Shu-Huei
SH
Liang
Chan-Jung
CJ
Kuan
I-I
II
Wu
Pei-Jhen
PJ
Pai
Pei-Ying
PY
Wu
Chau-Chung
CC
Chen
Yuh-Lien
YL
D000818:Animals; D002478:Cells, Cultured; D004731:Endotoxins / Q000633:toxicity*; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D009130:Muscle, Smooth / Q000166:cytology / Q000187:drug effects*; D011134:Polysaccharides / Q000494:pharmacology*; D020940:Reishi / Q000737:chemistry*; D017539:Tunica Intima / Q000187:drug effects*
D004731:Endotoxins; D011134:Polysaccharides; D018799:Intercellular Adhesion Molecule-1