Inhibitory capacity of different steroids on neutrophil migration across a bilayer of endothelial and bronchial epithelial cells

Eur J Pharmacol. 2003 Sep 23;477(3):261-7. doi: 10.1016/s0014-2999(03)02153-8.

Abstract

Neutrophil infiltration to the airway lumen is a common feature of respiratory inflammatory processes. The aim of this study was to evaluate whether different corticosteroids exert any selective effect on the migration of isolated neutrophils. A bilayer of cultured human endothelial and bronchial epithelial cells was used as a model for neutrophil migration through the blood-air barrier. Low spontaneous migration of neutrophils (2.8+/-0.9%, n=8; mean+/-S.E.M.) occurred, while in the absence of any steroid, a migration of 28.5+/-7.6% could be induced by lipopolysaccharide. Pre-incubation during 1 h of epithelial cells with dexamethasone, budesonide, or prednisolone (10(-10)-10(-4) M) showed in all instances a concentration-dependent inhibition following a bell-shaped curve. At 10(-7) M, both dexamethasone and budesonide were on the minimum effect peak of the bell-shaped curve. The peak for prednisolone was found at 10(-8) M. However, when steroid pre-incubation was extended to 4 h, a sigmoid curve was observed, with significant inhibition of migration at concentrations >10(-7) M. Steroids can inhibit neutrophil recruitment through two different pathways with distinct result, depending on the length of incubation time.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bronchi / cytology
  • Bronchi / drug effects*
  • Bronchi / physiology
  • Cell Line
  • Cell Movement / drug effects
  • Cell Movement / physiology
  • Dose-Response Relationship, Drug
  • Endothelium, Vascular / cytology
  • Endothelium, Vascular / drug effects*
  • Endothelium, Vascular / physiology
  • Epithelial Cells / cytology
  • Epithelial Cells / drug effects*
  • Epithelial Cells / metabolism
  • Humans
  • Interleukin-1 / pharmacology
  • Lipopolysaccharides / pharmacology
  • Neutrophil Infiltration / drug effects*
  • Neutrophil Infiltration / physiology
  • Neutrophils / drug effects
  • Neutrophils / metabolism
  • Pregnanes / pharmacology
  • Steroids / chemistry
  • Steroids / pharmacology*
  • Time Factors
  • Tumor Necrosis Factor-alpha / pharmacology

Substances

  • Interleukin-1
  • Lipopolysaccharides
  • Pregnanes
  • Steroids
  • Tumor Necrosis Factor-alpha