title: Andrographolide inhibits ICAM-1 expression and NF-κB activation in TNF-α-treated EA.hy926 cells.
abstract: Several lines of evidence indicate that inflammation and endothelial cell dysfunction are important initiating events in atherosclerosis. Tumor necrosis factor-α (TNF-α), a pro-inflammatory cytokine, induces the expression of cell adhesion molecules and results in monocyte adherence and atheromatous plaque formation. Andrographolide (AP) is a major bioactive diterpene lactone in Andrographis paniculata that has anti-inflammatory activity. A previous study demonstrated the role of heme oxygenase 1 (HO-1) in the inhibition of TNF-α-induced ICAM-1 expression by AP. The present study investigated the effect of AP on the IKK/NF-κB signaling pathway, which mediates TNF-α-induced ICAM-1 expression in EA.hy926 cells. Similar to the previous study, AP inhibited TNF-α-induced ICAM-1 mRNA and protein levels, its expression on the cell surface, and subsequent adhesion of HL-60 cells to EA.hy926 cells. AP inhibited TNF-α-induced κB inhibitor (IκB) kinase (IKK) and IκBα activation, p65 nuclear translocation, NF-κB and DNA binding activity, and promoter activity of ICAM-1. Although AP increased the intracellular cAMP concentration and induced the phosphorylation of cAMP response element-binding protein (CREB), knocking down CREB protein expression by transfecting the cells with CREB-specific small interfering RNA did not relieve the inhibition of ICAM-1 expression by AP. Taken together, these results suggest that AP down-regulates TNF-α-induced ICAM-1 expression at least in part via attenuation of activation of NF-κB in EA.hy926 cells rather than through activation of CREB. The results suggest that AP may have potential as a cardiovascular-protective agent.
authors.affiliation: Department of Health and Nutritional Biotechnology, Asia University, Taichung, Taiwan.
authors.forename: Che-Yi
authors.initials: CY
authors.lastname: Chao
authors.forename: Chong-Kuei
authors.initials: CK
authors.lastname: Lii
authors.forename: I-Ting
authors.initials: IT
authors.lastname: Tsai
authors.forename: Chien-Chun
authors.initials: CC
authors.lastname: Li
authors.forename: Kai-Li
authors.initials: KL
authors.lastname: Liu
authors.forename: Chia-Wen
authors.initials: CW
authors.lastname: Tsai
authors.forename: Haw-Wen
authors.initials: HW
authors.lastname: Chen
mesh_terms: D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002318:Cardiovascular Diseases / Q000517:prevention & control; D002448:Cell Adhesion / Q000187:drug effects; D002460:Cell Line; D004224:Diterpenes / Q000494:pharmacology*; D042783:Endothelial Cells / Q000187:drug effects / Q000502:physiology; D015870:Gene Expression / Q000187:drug effects*; D018922:HL-60 Cells; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000032:analysis / Q000235:genetics*; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D012333:RNA, Messenger / Q000032:analysis; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
chemical_list: D000893:Anti-Inflammatory Agents; D004224:Diterpenes; D016328:NF-kappa B; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; C030419:andrographolide