title: The compatible solute ectoine protects against nanoparticle-induced neutrophilic lung inflammation.
abstract: BACKGROUND
  Inflammatory reactions of the airways induced by nanoparticles of occupational and environmental origin contribute to organ-specific and systemic human diseases. Because this kind of exposure in modern societies is often unavoidable, a strategy of molecular prevention on an individual level could help to prevent inflammation-derived secondary diseases.
  
  
  OBJECTIVE
  To test whether the compatible solute ectoine [(S)-2-methyl-1,4,5,6-tetrahydropyrimidine-4-carboxylic acid], which is known to reduce cell stress effects on a molecular level, prevents nanoparticle-induced lung inflammation.
  
  
  METHODS
  Inflammatory parameters were studied in Fischer 344 rats treated with model carbon nanoparticles. The molecular effects of ectoin on proinflammatory signal transduction were demonstrated in the rat and in the human system using cultured lung epithelial cells.
  
  
  RESULTS
  Ectoine, given with or before the nanoparticles, dose-dependently reduced neutrophil inflammation in the lung. This preventive effect was not observed when lung inflammation was induced by bacterial lipopolysaccharide. Analyses of the underlying mode of action revealed that ectoine acted on lung epithelial cells. Ectoine administration inhibited nanoparticle-induced signaling, which is known to be responsible for proinflammatory reactions in rat lung epithelial cells in vitro as well as in vivo. These findings were corroborated and extended in experiments with cultured human bronchial epithelial cells in which ectoine inhibited nanoparticle-triggered cell signaling and IL-8 induction.
  
  
  CONCLUSIONS
  Because compatible solutes are compliant natural products without known toxic potential, we propose that this group of substances may be used for the prevention of particle-induced airway inflammation in humans.
authors.affiliation: Institut für Umweltmedizinische Forschung, Düsseldorf, Germany.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Sydlik
authors.forename: Inka
authors.initials: I
authors.lastname: Gallitz
authors.forename: Catrin
authors.initials: C
authors.lastname: Albrecht
authors.forename: Josef
authors.initials: J
authors.lastname: Abel
authors.forename: Jean
authors.initials: J
authors.lastname: Krutmann
authors.forename: Klaus
authors.initials: K
authors.lastname: Unfried