Quinine inhibits production of tumor necrosis factor-alpha from human alveolar macrophages.

N. Maruyama, Y. Kakuta, K. Yamauchi, Y. Ohkawara, T. Aizawa, T. Ohrui, M. Nara, T. Oshiro, I. Ohno, G. Tamura

Research output: Contribution to journalArticlepeer-review

36 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)514-520
Number of pages7
JournalAmerican journal of respiratory cell and molecular biology
Volume10
Issue number5
DOIs
Publication statusPublished - 1994 May

ASJC Scopus subject areas

  • Molecular Biology
  • Pulmonary and Respiratory Medicine
  • Clinical Biochemistry
  • Cell Biology

Fingerprint

Dive into the research topics of 'Quinine inhibits production of tumor necrosis factor-alpha from human alveolar macrophages.'. Together they form a unique fingerprint.

Cite this