Cytokine reducing effect of azelnidipine in human peripheral blood mononuclear cells.
Numerous clinical trials have shown that calcium channel blocker (CCB) therapy improves the clinical outcome in patients with cardiovascular diseases. Since the progression of several types of cardiovascular diseases is closely associated with inflammation, alleviation of inflammation may be one potential mechanism of those beneficial effects of CCB therapy. We examined whether a new CCB (azelnidipine) could influence the inflammatory response of human peripheral blood mononuclear cells (PBMCs), which are recruited to inflammatory lesions and modulate inflammation. We investigated whether azelnidipine affected intracellular signaling and cytokine production by phytohemagglutinin (PHA)-stimulated human PBMCs in vitro. PBMCs were obtained from 10 healthy volunteers and stimulated with PHA. Then relative intracellular calcium ion concentration ([Ca(2+)](i)) was assessed by fluorescence microscopy, and the production of monocyte chemoattractant protein-1 (MCP-1) and tumor necrosis factor-alpha (TNF-alpha) were measured by enzyme-linked immunosorbent assay. Stimulation with PHA significantly raised [Ca(2+)](i) and enhanced the production of MCP-1 and TNF-alpha by human PBMCs. Azelnidipine significantly diminished the PHA-induced rise of [Ca(2+)](i), and the production of MCP-1 and TNF-alpha. These findings indicate that azelnidipine might have an anti-inflammatory influence on human PBMCs, although the mechanisms and the difference from other CCBs still remain unclear and further exploration should be required.
Miura
Ryuzea
R
Department of Cardiovascular Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan. ryuzeamiura@mail.goo.ne.jp
Nakamura
Kazufumi
K
Miura
Daiji
D
Miura
Aya
A
Kajiya
Masahito
M
Hisamatsu
Kenichi
K
Nagase
Satoshi
S
Morita
Hiroshi
H
Kusano
Kengo Fukushima
KF
Matsubara
Hiromi
H
Ohe
Tohru
T
Ito
Hiroshi
H
D001383:Azetidinecarboxylic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D016207:Cytokines / Q000097:blood*; D004095:Dihydropyridines / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood*; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism
D002121:Calcium Channel Blockers; D016207:Cytokines; D004095:Dihydropyridines; D018836:Inflammation Mediators; D001383:Azetidinecarboxylic Acid; C061679:azelnidipine