Effects of benidipine, a dihydropyridine-Ca2+ channel blocker, on expression of cytokine-induced adhesion molecules and chemoattractants in human aortic endothelial cells.
Benidipine hydrochloride (benidipine) is a dihydropyridine-Ca2+ channel blocker with antioxidant properties. We examined the effects of benidipine on cytokine-induced expression of adhesion molecules and chemokines, which play important roles in the adhesion of monocytes to endothelium. Pretreatment of human aortic endothelial cells (HAECs) with benidipine (0.3-10 micromol/l) for 24 h significantly suppressed cytokine-induced vascular cell adhesion molecule-1 (VCAM-1) and intracellular cell adhesion molecule-1 (ICAM-1) mRNA and protein expression, resulting in reduced adhesion of THP-1 monocytes. Benidipine also suppressed induction of monocyte chemoattractant protein (MCP)-1 and interleukin-8. Benidipine inhibited redox-sensitive transcriptional nuclear factor-kappaB (NF-kappaB) pathway, as determined by Western blotting of inhibitory kappaB (IkappaB) phosphorylation and luciferase reporter assay. Results of analysis using optical isomers of benidipine and antioxidants suggested that these inhibitory effects were dependent on pharmacological effects other than Ca2+ antagonism such as antioxidant effects. Benidipine may thus have anti-inflammatory properties and benefits for in the treatment of atherosclerosis.
Matsubara
Masahiro
M
Department of Pharmaceutical Research Institute, Kyowa Hakko Kogyo Co., Ltd., 1188 Shimotogari, Nagaizumi-cho, Sunto-gun, Shizuoka 411-8731, Japan. masahiro.matsubara@kyowa.co.jp
Hasegawa
Kazuhide
K
D000975:Antioxidants / Q000494:pharmacology; D001011:Aorta / Q000166:cytology; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism; D002630:Chemotactic Factors / Q000235:genetics / Q000378:metabolism*; D016207:Cytokines / Q000494:pharmacology*; D004095:Dihydropyridines / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D007375:Interleukin-1 / Q000494:pharmacology; D016328:NF-kappa B / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013237:Stereoisomerism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism
D000975:Antioxidants; C111835:CCL2 protein, human; D002121:Calcium Channel Blockers; D015815:Cell Adhesion Molecules; D018932:Chemokine CCL2; D002630:Chemotactic Factors; D016207:Cytokines; D004095:Dihydropyridines; D007375:Interleukin-1; D016328:NF-kappa B; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; C061004:benidipine; C038806:1,4-dihydropyridine