Carvedilol, a nonselective β-blocker, suppresses the production of tumor necrosis factor and tissue factor by inhibiting early growth response factor-1 expression in human monocytes in vitro

Yuichiro Mizuochi, Kenji Okajima, Naoaki Harada, Perenlei Molor-Erdene, Mitsuhiro Uchiba, Hidefumi Komura, Takako Tsuda, Hirotada Katsuya

研究成果: Article査読

21 被引用数 (Scopus)

抄録

Tumor necrosis factor (TNF) and tissue factor (TF) produced by monocytes and macrophages have been shown to be among the aggravating factors for chronic heart failure (CHF), because they induce cardiac dysfunction and thrombotic complications, respectively. Carvedilol, a nonselective β-adrenoceptor antagonist with α1- adrenoceptor blockade action, has been demonstrated to improve the outcome of patients with severe CHF, suggesting that carvedilol might inhibit the production of TNF and TF. In this study, this possibility is examined using isolated human monocytes stimulated with lipopolysaccharide (LPS) in vitro. Carvedilol (10 μM) significantly inhibited LPS-induced production of TNF and TF by monocytes, whereas prazosin (a selective α1-adrenoceptor antagonist), bisoprolol (a selective β1-adrenoceptor antagonist), ICI-118,551 (a selective β2-adrenoceptor antagonist), and arotinolol (a nonselective β-adrenoceptor antagonist with α1-adrenoceptor blockade action) did not. Carvedilol inhibited both expression of early growth response factor-1 (Egr-1) and phosphorylation of extracellular signal-regulated kinase (ERK) 1/2, but it did not inhibit activation of either nuclear factor-κB or activator protein-1 in monocytes stimulated with LPS. These results suggest that carvedilol inhibits LPS-induced production of TNF and TF by inhibiting activation of the ERK1/2-Egr-1 pathway independent of its adrenoceptor inhibitory activities in monocytes.

本文言語English
ページ(範囲)223-230
ページ数8
ジャーナルTranslational Research
149
4
DOI
出版ステータスPublished - 04-2007
外部発表はい

All Science Journal Classification (ASJC) codes

  • Public Health, Environmental and Occupational Health
  • Biochemistry, medical
  • Physiology (medical)

フィンガープリント 「Carvedilol, a nonselective β-blocker, suppresses the production of tumor necrosis factor and tissue factor by inhibiting early growth response factor-1 expression in human monocytes in vitro」の研究トピックを掘り下げます。これらがまとまってユニークなフィンガープリントを構成します。

引用スタイル