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The Compatible Solute Ectoine Protects against Nanoparticle-induced Neutrophilic Lung Inflammation

¹ Environmental Health Research Institute (IUF) at the Heinrich-Heine-University Düsseldorf gGmbH, Düsseldorf, Germany

Correspondence and requests for reprints should be addressed to Dr. Klaus Unfried, Ph.D., Institut für Umweltmedizinische Forschung (IUF), Auf'm Hennekamp 50, 40225 Düsseldorf, Germany. E-mail: klaus.unfried{at}uni-duesseldorf.de

Rationale: 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.

Objectives: 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.

Measurements and Main 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.

Key Words: lung epithelium • mitogen-activated protein kinases • IL-8

AT A GLANCE COMMENTARY Scientific Knowledge on the Subject Compatible solutes are considered as stabilizers of macromolecules, including membrane structures. There are few indications that this group of substances could be used for the prevention or therapy of diseases. What This Study Adds to the Field Ectoine applied to the lung prevents neutrophil inflammation induced by environmentally relevant model nanoparticles.