Metformin, an antidiabetic agent, suppresses the production of tumor necrosis factor and tissue factor by inhibiting early growth response factor-1 expression in human monocytes in vitro

Masatoku Arai, Mitsuhiro Uchiba, Hidefumi Komura, Yuichiro Mizuochi, Naoaki Harada, Kenji Okajima

Research output: Contribution to journalArticle

77 Citations (Scopus)

Abstract

Metformin, an antidiabetic agent, has been shown to reduce atherothrombotic disease in diabetic patients independent of antihyperglycemic effect. Recent studies have demonstrated that metformin attenuates the proinflammatory responses in human vascular wall cells and macrophages. However, the detailed molecular mechanisms underlying these therapeutic effects remain unclear. In the present study, we investigated the effects of metformin on tumor necrosis factor (TNF) production and tissue factor (TF) expression in isolated human monocytes stimulated with lipopolysaccharide (LPS) or oxidized low-density lipoprotein (oxLDL). Metformin significantly inhibited both TNF production and TF expression in isolated human monocytes stimulated with LPS or oxLDL. Metformin also significantly inhibited TNF and TF mRNA in human monocytes stimulated with LPS. Although metformin did not inhibit the activation of either nuclear factor- κB or activator protein-1, it inhibited the expression of early growth response factor-1 (Egr-1) and phosphorylation of extracellular signal-regulated protein kinase (ERK) 1/2 in monocytes stimulated with LPS or oxLDL. These results suggest that metformin may attenuate the inflammatory responses, at least in part, by suppressing the production of both TNF and TF through the inhibition of the ERK1/2-Egr-1 pathway in human monocytes.

Original languageEnglish
Pages (from-to)206-213
Number of pages8
JournalJournal of Pharmacology and Experimental Therapeutics
Volume334
Issue number1
DOIs
Publication statusPublished - 01-07-2010
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Pharmacology

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