Quinine inhibits production of tumor necrosis factor-alpha from human alveolar macrophages.
Although tumor necrosis factor-alpha (TNF-alpha) produced by alveolar macrophages plays a key role in acute and chronic inflammatory states of the lung, the regulation of TNF-alpha synthesis remains to be elucidated. Recently, a K channel blocker, quinine, has been reported to inhibit cell proliferation and protein synthesis in lymphocytes, implicating physiologic roles for K channels in lymphocytes. The effect of quinine on protein synthesis in human alveolar macrophages, however, has not been determined, although alveolar macrophages have been reported to have two types of K channels. Therefore, we investigated the effect of quinine on TNF-alpha production from human alveolar macrophages. The production of TNF-alpha was induced by lipopolysaccharide (LPS) stimulation. We obtained the following results. First, LPS induced time-dependent activation of both types of K channels. Second, quinine inhibited TNF-alpha release in a dose-dependent fashion at concentrations of 50 to 200 microM, concentrations capable of blocking both types of K channels, with no appreciable reduction of phagocytosis of latex beads. Third, the compound remarkably inhibited the expression of TNF-alpha mRNA without any appreciable effect on the expression of beta-actin mRNA. These results indicate that both types of K channels are activated by stimulation with LPS and that quinine, at concentrations required to inhibit K channels, specifically blocks TNF-alpha production of human alveolar macrophages at the level of gene transcription.
Maruyama
N
N
First Department of Internal Medicine, Tohoku University School of Medicine, Sendai, Japan.
Kakuta
Y
Y
Yamauchi
K
K
Ohkawara
Y
Y
Aizawa
T
T
Ohrui
T
T
Nara
M
M
Oshiro
T
T
Ohno
I
I
Tamura
G
G
D000328:Adult; D015152:Blotting, Northern; D002118:Calcium / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D016676:Macrophages, Alveolar / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D008875:Middle Aged; D010587:Phagocytosis / Q000187:drug effects; D015221:Potassium Channels / Q000187:drug effects; D011803:Quinine / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000235:genetics
D008070:Lipopolysaccharides; D015221:Potassium Channels; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D011803:Quinine; D002118:Calcium