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

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)223-230
Number of pages8
JournalTranslational Research
Volume149
Issue number4
DOIs
Publication statusPublished - 04-2007
Externally publishedYes

All Science Journal Classification (ASJC) codes

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

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