Cytokine reducing effect of azelnidipine in human peripheral blood mononuclear cells.

Abstract

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.

• Authors: Ryuzea Miura, Kazufumi Nakamura, Daiji Miura, Aya Miura, Masahito Kajiya, Kenichi Hisamatsu, Satoshi Nagase, Hiroshi Morita, Kengo Fukushima Kusano, Hiromi Matsubara, Tohru Ohe, Hiroshi Ito
• Journal: Biological & pharmaceutical bulletin (Biol Pharm Bull) Vol. 33 Issue 7 Pg. 1148-51 ( 2010) ISSN: 1347-5215 [Electronic] Japan
• PMID: 20606305 (Publication Type: Journal Article)

Chemical References

• Calcium Channel Blockers
• Cytokines
• Dihydropyridines
• Inflammation Mediators
• Azetidinecarboxylic Acid
• azelnidipine

Topics

• Azetidinecarboxylic Acid (analogs & derivatives, pharmacology)
• Calcium Channel Blockers (pharmacology)
• Cytokines (blood)
• Dihydropyridines (pharmacology)
• Enzyme-Linked Immunosorbent Assay
• Humans
• Inflammation Mediators (blood)
• Monocytes (drug effects, metabolism)