Ethyl pyruvate modulates adhesive and secretory reactions in human lung epithelial cells

Life Sci. 2009 Jun 5;84(23-24):805-9. doi: 10.1016/j.lfs.2009.03.012. Epub 2009 Apr 2.

Abstract

Aims: Ethyl pyruvate (EtP) may prolong survival and ameliorate organ dysfunction in a variety of models of critical illness, e.g. severe sepsis and acute respiratory syndrome, by modulation of the expression of inflammatory mediators. Here, we studied the effects of EtP on the reactions in and between human neutrophils and lung epithelial (A549) cells in vitro.

Main methods: Neutrophil adhesion to, surface expression of ICAM-1 and VCAM-1 on, and release of IL-8 and G-CSF from A549 cells were measured by ELISA after stimulation with IL-1 beta or TNFalpha.

Key findings: After treatment of A549 cells with EtP, a substantial reduction in the cytokine-induced adhesion of neutrophils to monolayers was noted, whereas sodium pyruvate (NaP) conferred no reduction. Likewise, treatment with 2.5-10 mM EtP (but not NaP) reduced ICAM-1 and VCAM-1 expression in a dose-dependent fashion. The generation of cytokines of significance for adhesive and proliferative events in host defense, IL-8 and G-CSF, was also potently impaired by EtP.

Significance: Exposure of lung epithelial cells to 2.5-10 mM EtP inhibited the generation of inflammatory-regulating cytokines IL-8 and G-CSF, reduced ICAM-1 and VCAM-1 expression and impeded the adhesiveness of neutrophils to lung epithelial cells. These are reactions of significance for early inflammatory responses in the lung, suggesting a role for EtP as a treatment for acute pulmonary conditions.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Adhesion / drug effects
  • Cell Adhesion / physiology*
  • Cell Line, Tumor
  • Epithelial Cells / drug effects
  • Epithelial Cells / metabolism*
  • Granulocyte Colony-Stimulating Factor / antagonists & inhibitors
  • Granulocyte Colony-Stimulating Factor / metabolism
  • Humans
  • Intercellular Adhesion Molecule-1 / biosynthesis
  • Interleukin-1beta / antagonists & inhibitors
  • Interleukin-1beta / physiology
  • Interleukin-8 / antagonists & inhibitors
  • Interleukin-8 / metabolism
  • Lung / cytology
  • Lung / drug effects
  • Lung / metabolism*
  • Neutrophils / drug effects
  • Neutrophils / metabolism
  • Pyruvates / pharmacology*
  • Respiratory Mucosa / cytology*
  • Respiratory Mucosa / drug effects
  • Respiratory Mucosa / metabolism*
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors
  • Tumor Necrosis Factor-alpha / physiology
  • Vascular Cell Adhesion Molecule-1 / biosynthesis

Substances

  • Interleukin-1beta
  • Interleukin-8
  • Pyruvates
  • Tumor Necrosis Factor-alpha
  • Vascular Cell Adhesion Molecule-1
  • ethyl pyruvate
  • Intercellular Adhesion Molecule-1
  • Granulocyte Colony-Stimulating Factor