Artemisinin inhibits monocyte adhesion to HUVECs through the NF-κB and MAPK pathways in vitro.
The adhesion of monocytes to human umbilical vein endothelial cells (HUVECs) plays a crucial role in the initiation of atherosclerosis. Intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) are two important molecules involved in the adhesion of monocytes to HUVECs. Previous studies have suggested that artemisinin, apart from an anti-malarial agent, also has other effects. In the present study, we found that artemisinin significantly decreased the adhesion of monocytes to tumor necrosis factor-α (TNF-α)-stimulated HUVECs in a dose-dependent manner and suppressed the mRNA and protein level of ICAM-1 and VCAM-1 in the TNF-α-stimulated HUVECs. In addition, the nuclear factor-κB (NF-κB) inhibitor, Bay 11-7082, and mitogen-activated protein kinase (MAPK) inhibitors (SB203580 and U0126) respectively reduced the adhesion of monocytes to TNF-α-stimulated HUVECs, and suppressed ICAM-1 and VCAM-1 expression in TNF-α stimulated HUVECs. Moreover, artemisinin impeded the activation of the NF-κB and MAPK signaling pathways. Furthermore, Bay 11-7082 significantly decreased the phosphorylation of levels extracellular signal-regulated protein kinase (ERK)1/2, p38 and c-Jun N-terminal kinase (JNK). Taken together, the findings of our study indicated that artemisinin blocked monocyte adhesion to TNF-α-stimulated to HUVECs by downregulating ICAM-1 and VCAM-1 expression in the TNF-α-stimulated HUVECs. Artemisinin may thus have potential for use in the protection against the early development of atherosclerotic lesions.
Department of Cardiology, Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, P.R. China.
Yue
Y
Wang
Department of Cardiology, Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, P.R. China.
Jiatian
J
Cao
Department of Cardiology, Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, P.R. China.
Yuqi
Y
Fan
Department of Cardiology, Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, P.R. China.
Yushui
Y
Xie
Department of Cardiology, Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, P.R. China.
Zuojun
Z
Xu
Department of Cardiology, Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, P.R. China.
Zhaofang
Z
Yin
Department of Cardiology, Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, P.R. China.
Lin
L
Gao
Department of Cardiology, Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, P.R. China.
Changqian
C
Wang
D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D037621:Artemisinins / Q000494:pharmacology*; D002070:Butadienes / Q000494:pharmacology; D002448:Cell Adhesion / Q000187:drug effects; D002460:Cell Line; D018920:Coculture Techniques; D005786:Gene Expression Regulation; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D009000:Monocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D016328:NF-kappa B / Q000235:genetics* / Q000378:metabolism; D009570:Nitriles / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D015398:Signal Transduction; D013450:Sulfones / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000494:pharmacology; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism
C434003:3-(4-methylphenylsulfonyl)-2-propenenitrile; D000893:Anti-Inflammatory Agents; D037621:Artemisinins; D002070:Butadienes; C573420:ICAM1 protein, human; D007093:Imidazoles; D016328:NF-kappa B; D009570:Nitriles; D047428:Protein Kinase Inhibitors; D011725:Pyridines; D013450:Sulfones; D014409:Tumor Necrosis Factor-alpha; C113580:U 0126; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; C031327:artemisinin; D048031:JNK Mitogen-Activated Protein Kinases; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; C093642:SB 203580