Induction of heme oxygenase 1 and inhibition of tumor necrosis factor alpha-induced intercellular adhesion molecule expression by andrographolide in EA.hy926 cells.
Andrographolide is the most abundant diterpene lactone in Andrographis paniculata, which is widely used as a traditional medicine in Southeast Asia. Heme oxygenase 1 (HO-1) is an antioxidant enzyme encoded by a stress-responsive gene. HO-1 has been reported to inhibit the expression of adhesion molecules in vascular endothelial cells (EC). Intercellular adhesion molecule (ICAM-1) is an inflammatory biomarker that is involved in the adhesion of monocytes to EC. In this study, we investigated the effect of andrographolide on the expression of ICAM-1 induced by tumor necrosis factor alpha (TNF-alpha) in EA.hy926 cells and the possible mechanisms involved. Andrographolide (2.5-7.5 microM) inhibited the TNF-alpha-induced expression of ICAM-1 in a dose-dependent manner and resulted in a decrease in HL-60 cell adhesion to EA.hy926 cells (p < 0.05). In parallel, andrographolide significantly induced the expression of HO-1 in a concentration-dependent fashion (p < 0.05). Andrographolide increased the rate of nuclear translocation of nuclear factor erythroid 2-related 2 (Nrf2) and induced antioxidant response element-luciferase reporter activity. Transfection with HO-1-specific small interfering RNA knocked down HO-1 expression, and the inhibition of expression of ICAM-1 by andrographolide was significantly reversed. These results suggest that stimulation of Nrf2-dependent HO-1 expression is involved in the suppression of TNF-alpha-induced ICAM-1 expression exerted by andrographolide.
Department of Nutrition, China Medical University, Taichung, Taiwan.
Ai-Lin
AL
Yu
Chia-Yang
CY
Lu
Tsu-Shing
TS
Wang
Chia-Wen
CW
Tsai
Kai-Li
KL
Liu
Yi-Ping
YP
Cheng
Hebron C
HC
Chang
Chong-Kuei
CK
Lii
Haw-Wen
HW
Chen
D021581:Active Transport, Cell Nucleus / Q000187:drug effects; D035685:Andrographis / Q000737:chemistry; D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects; D045744:Cell Line, Tumor; D004224:Diterpenes / Q000494:pharmacology*; D015536:Down-Regulation / Q000187:drug effects*; D015870:Gene Expression / Q000187:drug effects; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D018922:HL-60 Cells; D051547:Heme Oxygenase-1 / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics* / Q000378:metabolism; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism; D010936:Plant Extracts / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism*
D004224:Diterpenes; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; D010936:Plant Extracts; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; C030419:andrographolide; D051547:Heme Oxygenase-1