title: Propofol inhibits T-helper cell type-2 differentiation by inducing apoptosis via activating gamma-aminobutyric acid receptor.
abstract: Propofol has been shown to attenuate airway hyperresponsiveness in asthma patients. Our previous study showed that it may alleviate lung inflammation in a mouse model of asthma. Given the critical role of T-helper cell type-2 (Th2) differentiation in asthma pathology and the immunomodulatory role of the gamma-aminobutyric acid type A (GABAA) receptor, we hypothesized that propofol could alleviate asthma inflammation by inhibiting Th2 cell differentiation via the GABA receptor.
  
  
  
  For in vivo testing, chicken ovalbumin-sensitized and challenged asthmatic mice were used to determine the effect of propofol on Th2-type asthma inflammation. For in vitro testing, Th2-type cytokines as well as the cell proliferation and apoptosis were measured to assess the effects of propofol on Th2 cell differentiation and determine the underlying mechanisms.
  
  
  
  We found that propofol significantly decreased inflammatory cell counts and interleukin-4 and inflammation score in vivo. Propofol, but not intralipid, significantly reduced the Th2-type cytokine interleukin-5 secretion and caused Th2 cell apoptosis without obvious inhibition of proliferation in vitro. A GABA receptor agonist simulated the effect of propofol, whereas pretreatment with an antagonist reversed this effect.
  
  
  
  This study demonstrates that the antiinflammatory effects of propofol on Th2-type asthma inflammation in mice are mediated by inducing apoptosis without compromising proliferation during Th2 cell differentiation via activation of the GABA receptor.
authors.affiliation: Department of Anesthesiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Jingxia
authors.initials: J
authors.lastname: Meng
authors.affiliation: Department of Anesthesiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Xin
authors.affiliation: Department of Anesthesiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Anesthesiology, Beijing Aerospace General Hospital, Beijing, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Immunology, Institute of Basic Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Huang
authors.affiliation: Department of Anesthesiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Yuguang
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Department of Anesthesiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. Electronic address: zhaojing1009@aliyun.com.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhao
mesh_terms: D000818:Animals; D018927:Anti-Asthmatic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects*; D001249:Asthma / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism; D005260:Female; D051379:Mice; D008807:Mice, Inbred BALB C; D015742:Propofol / Q000494:pharmacology* / Q000627:therapeutic use; D011963:Receptors, GABA-A / Q000378:metabolism*; D018418:Th2 Cells / Q000187:drug effects* / Q000502:physiology
chemical_list: D018927:Anti-Asthmatic Agents; D015415:Biomarkers; D016207:Cytokines; D011963:Receptors, GABA-A; D015742:Propofol
keywords: Airway; Asthma; GABA receptor; Inflammation; Propofol; Th2 cell differentiation