Rebamipide suppresses mite-induced asthmatic responses in NC/Nga mice

Am J Physiol Lung Cell Mol Physiol. 2015 Oct 15;309(8):L872-8. doi: 10.1152/ajplung.00194.2015. Epub 2015 Aug 21.

Abstract

Allergic asthma caused by continuous allergen exposure evokes allergen-specific Th2 responses and is characterized by chronic airway inflammation and hyperresponsiveness. A previous report showed that rebamipide improved asthmatic symptoms in an ovalbumin/trypsin mice model. However, it is still unclear how rebamipide exerts its effects in asthma. In this study, rebamipide improved the asthmatic responses induced by mite exposure in NC/Nga mice, revealing the mechanism of this therapeutic effect. Rebamipide suppressed the infiltration of eosinophils into the airways and lung as well as attenuating the production of reactive oxygen species in tissues. In addition to these anti-inflammatory effects, rebamipide inhibited the production of IL-33, a member of the IL-1 family that drives the subsequent production of Th2-associated cytokines. These observations identify the point where rebamipide exerts its suppressive action on asthma and suggest that rebamipide has therapeutic potential in preventing mite-induced asthma.

Keywords: IL-33; asthma; eosinophil; reactive oxygen species; rebamipide.

MeSH terms

  • 8-Hydroxy-2'-Deoxyguanosine
  • Alanine / analogs & derivatives*
  • Alanine / therapeutic use
  • Allergens / administration & dosage
  • Animals
  • Antigens, Dermatophagoides / administration & dosage
  • Antioxidants / therapeutic use
  • Asthma / drug therapy*
  • Asthma / etiology
  • Asthma / pathology
  • Bronchoalveolar Lavage Fluid / cytology
  • Bronchoalveolar Lavage Fluid / immunology
  • Chemokine CCL11 / genetics
  • Chemokine CCL11 / metabolism
  • Chemokine CCL24 / genetics
  • Chemokine CCL24 / metabolism
  • Cytokines / genetics
  • Cytokines / metabolism
  • Deoxyguanosine / analogs & derivatives
  • Deoxyguanosine / metabolism
  • Disease Models, Animal
  • Interleukin-33 / genetics
  • Interleukin-33 / metabolism
  • Lung / drug effects
  • Lung / pathology
  • Lung / physiopathology
  • Macrophages / drug effects
  • Macrophages / immunology
  • Male
  • Mice
  • Quinolones / therapeutic use*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Respiratory Hypersensitivity / drug therapy

Substances

  • Allergens
  • Antigens, Dermatophagoides
  • Antioxidants
  • Ccl11 protein, mouse
  • Ccl24 protein, mouse
  • Chemokine CCL11
  • Chemokine CCL24
  • Cytokines
  • Il33 protein, mouse
  • Interleukin-33
  • Quinolones
  • RNA, Messenger
  • 8-Hydroxy-2'-Deoxyguanosine
  • Deoxyguanosine
  • rebamipide
  • Alanine