Dexmedetomidine mitigate acute lung injury by inhibiting IL-17-induced inflammatory reaction

Immunobiology. 2018 Jan;223(1):32-37. doi: 10.1016/j.imbio.2017.10.017. Epub 2017 Oct 7.

Abstract

Interleukin-17 (IL-17) is considered to play an important role in the pathogenesis of a number of inflammatory conditions. Previous studies demonstrated that intranasal injections of IL-17 resulted in pulmonary inflammation and lung damage, we therefore hypothesize that dexmedetomidine, a potent α2 adrenergic receptor agonist that shows anti-inflammation effects in several animal models of inflammation, would attenuate IL-17 induced lung injury. We examined the lung damage using a histological approach, and assessed the number of lung-infiltrating neutrophils in the bronchoalveolar lavage fluid. We then compared the production of selected cytokines by measuring their serum concentration after various treatments. Finally, we evaluated the expression of selected inflammatory genes and activation of NF-κB in the lung epithelial cells, using real-time PCR and western blot assay, respectively. In every aspect of pulmonary inflammation investigated, dexmedetomidine significantly and dose-dependently attenuated the inflammatory effects of IL-17. Our results not only give a comprehensive description of the protective action of dexmedetomidine on IL-17 induced acute lung injury, but also provide insights to the underlying cellular and molecular mechanisms.

Keywords: Dexmedetomidine; IL-17; Inflammation; Lung injury; NF-κB.

MeSH terms

  • Acute Lung Injury / drug therapy*
  • Adrenergic alpha-2 Receptor Agonists / therapeutic use*
  • Animals
  • Anti-Inflammatory Agents / therapeutic use*
  • Bronchoalveolar Lavage Fluid / immunology
  • Cell Movement
  • Cells, Cultured
  • Cytokines / metabolism
  • Dexmedetomidine / therapeutic use*
  • Epithelial Cells / drug effects
  • Epithelial Cells / immunology*
  • Inflammation / drug therapy*
  • Interleukin-17 / metabolism
  • Lung / pathology
  • Mice
  • Mice, Inbred Strains
  • NF-kappa B / metabolism
  • Neutrophils / drug effects
  • Neutrophils / immunology*

Substances

  • Adrenergic alpha-2 Receptor Agonists
  • Anti-Inflammatory Agents
  • Cytokines
  • Interleukin-17
  • NF-kappa B
  • Dexmedetomidine