Dilazep decreases lipopolysaccharide-induced nitric oxide and TNF-alpha synthesis in RAW 264 cells.
Dilazep dihydrochloride (dilazep) is used to treat ischemic dysfunction, although the mechanisms underlying the anti-inflammatory effects of the drug have not yet been elucidated. The present study evaluated the anti-inflammatory effect of dilazep. Dilazep suppressed the production of nitric oxide (NO) and the expression of TNF-alpha mRNA by lipopolysaccharide (LPS) in RAW 264 cells. However, 1400W, an inducible NO synthase inhibitor, suppressed the production of NO but did not suppress the expression of TNF-alpha mRNA following treatment with LPS. Caffeine, an adenosine antagonist, restored LPS-stimulated NO synthesis, which is suppressed by dilazep. Therefore, these observations may suggest that the suppression of NO synthesis after dilazep treatment in RAW 264 cells is caused by the inhibition of TNF-alpha expression via adenosine receptors.
Nakatsuka
Ryusuke
R
Department of Pharmacology, Osaka Dental University, Hirakata, Osaka, Japan. nakatsur@takii.kmu.ac.jp
Nozaki
Tadashige
T
Shinohara
Mitsuko
M
Ohura
Kiyoshi
K
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D002461:Cell Line, Transformed; D004109:Dilazep / Q000494:pharmacology*; D015536:Down-Regulation / Q000187:drug effects*; D008070:Lipopolysaccharides / Q000633:toxicity; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D009994:Osmolar Concentration; D058915:Purinergic P1 Receptor Antagonists; D012333:RNA, Messenger / Q000378:metabolism; D018047:Receptors, Purinergic P1 / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D008070:Lipopolysaccharides; D058915:Purinergic P1 Receptor Antagonists; D012333:RNA, Messenger; D018047:Receptors, Purinergic P1; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D004109:Dilazep