title: Ketamine Inhalation Ameliorates Ovalbumin-Induced Murine Asthma by Suppressing the Epithelial-Mesenchymal Transition.
abstract: BACKGROUND Asthma accounts for 0.4% of all deaths worldwide, a figure that increases annually. Ketamine induces bronchial smooth muscle relaxation, and increasing evidence suggests that its anti-inflammatory properties might protect against lung injury and ameliorate asthma. However, there is a lack of evidence of the usefulness and mechanism of ketamine in acute asthma exacerbation. This study aimed to analyze the therapeutic effects and mechanism of action of ketamine on acute ovalbumin (OVA)-induced murine asthma. MATERIAL AND METHODS In vivo, BALB/c mice with OVA-induced asthma were treated with or without ketamine (25 or 50 mg/mL). Serum, lung sections, and mononuclear cell suspensions from the lung were collected for histological, morphometric, immunofluorescence, microRNA, quantitative polymerase chain reaction, regulatory T cell identification, cytokine, and Western blotting analyses. In vitro, bronchial epithelial cells were cultured to analyze the effect and mechanism of ketamine on epithelial-mesenchymal transition (EMT) and transforming growth factor-β (TGF-β) signaling. RESULTS The inhalation of ketamine 25 or 50 mg/mL markedly suppressed OVA-induced airway hyper-responsiveness and airway inflammation, significantly increased the percentage of CD4+CD25+ T cells, and significantly decreased OVA-induced up-regulation of TGF-β1 and the EMT. MiR-106a was present at higher amounts in OVA-induced lung samples and was suppressed by ketamine treatment. The in vitro results showed that TGF-β1-induced EMT was suppressed by ketamine via miR-106a level regulation. CONCLUSIONS Ketamine ameliorates lung fibrosis in OVA-induced asthmatic mice by suppressing EMT and regulating miR-106a level, while ketamine inhalation might be a new therapeutic approach to the treatment of allergic asthma.
authors.affiliation: Department of Anesthesiology, Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, China (mainland).
authors.forename: Li
authors.initials: L
authors.lastname: Song
authors.affiliation: Department of Vascular and Thyroid Surgery, Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, China (mainland).
authors.forename: Shi
authors.initials: S
authors.lastname: Sen
authors.affiliation: Department of Pharmacy, Southwest Medical University, Luzhou, Sichuan, China (mainland).
authors.forename: Yuhong
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Anesthesiology, Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, China (mainland).
authors.forename: Jun
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Department of Anesthesiology, Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, China (mainland).
authors.forename: Liqun
authors.initials: L
authors.lastname: Mo
authors.affiliation: Department of Vascular and Thyroid Surgery, Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, China (mainland).
authors.forename: Yanzheng
authors.initials: Y
authors.lastname: He
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D001249:Asthma / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D001992:Bronchoalveolar Lavage Fluid; D004195:Disease Models, Animal; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D005260:Female; D007649:Ketamine / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism; D010047:Ovalbumin; D011658:Pulmonary Fibrosis / Q000188:drug therapy / Q000473:pathology; D011897:Random Allocation; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D000893:Anti-Inflammatory Agents; D035683:MicroRNAs; C543896:Mirn106 microRNA, mouse; D053773:Transforming Growth Factor beta1; D007649:Ketamine; D010047:Ovalbumin