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MTOR-Mediated Autophagy Is Involved in the Protective Effect of Ketamine on Allergic Airway Inflammation.
- Source :
-
Journal of immunology research [J Immunol Res] 2019 Jan 09; Vol. 2019, pp. 5879714. Date of Electronic Publication: 2019 Jan 09 (Print Publication: 2019). - Publication Year :
- 2019
-
Abstract
- Unresolved inflammation underpins the pathogenesis of allergic airway diseases, such as asthma. Ketamine, accepted as a promising therapy for resistant asthma, has been demonstrated to attenuate allergic airway inflammation. However, the anti-inflammatory mechanism by ketamine in this setting is largely unknown. We aimed to investigate whether autophagy was involved in the protective effect of ketamine on allergic airway inflammation. Female C57BL/6 mice were sensitized to ovalbumin (OVA) and treated with ketamine at 25, 50, or 100 mg/kg prior to OVA challenge. In this model, the pulmonary morphological findings and airway inflammation were significantly inhibited at 50 mg/kg but not at 25 or 100 mg/kg. Moreover, 50 mg/kg ketamine abrogated the increased concentrations of inflammatory cytokines in bronchoalveolar lavage fluid (BALF) of allergic mice, as well as activated the expression of phosphorylated mammalian target of rapamycin (p-MTOR) and inhibited autophagy in allergic mice. To confirm whether the effect of 50 mg/kg ketamine on asthma was mediated by inhibiting autophagy, rapamycin was administered to mice sensitized to OVA and exposed to 50 mg/kg ketamine. All of the effect of 50 mg/kg ketamine was reversed by rapamycin treatment, including increased p-MTOR and decreased autophagy. Taken together, the present study demonstrates that 50 mg/kg ketamine inhibits allergic airway inflammation by suppressed autophagy, and this effect is mediated by the activation of MTOR in the lungs of allergic mice.
- Subjects :
- Animals
Asthma immunology
Bronchoalveolar Lavage Fluid
Cytokines immunology
Disease Models, Animal
Female
Lung immunology
Lung physiopathology
Mice
Mice, Inbred C57BL
Ovalbumin
Anti-Inflammatory Agents pharmacology
Asthma drug therapy
Autophagy drug effects
Inflammation immunology
Ketamine pharmacology
TOR Serine-Threonine Kinases immunology
Subjects
Details
- Language :
- English
- ISSN :
- 2314-7156
- Volume :
- 2019
- Database :
- MEDLINE
- Journal :
- Journal of immunology research
- Publication Type :
- Academic Journal
- Accession number :
- 30729138
- Full Text :
- https://doi.org/10.1155/2019/5879714