title: Rapamycin inhibition of eosinophil differentiation attenuates allergic airway inflammation in mice.
abstract: OBJECTIVE
  The mammalian target of rapamycin (mTOR) signalling pathway regulates immune responses, and promotes cell growth and differentiation. Inhibition of mTOR with rapamycin modulates allergic asthma, while the underlying molecular mechanisms remain elusive. Here, we demonstrate that rapamycin, effectively inhibits eosinophil differentiation, contributing to its overall protective role in allergic airway inflammation.
  
  
  METHODS
  Rapamycin was administered in a mouse model of ovalbumin-induced allergic airway inflammation, and the eosinophil differentiation was analysed in vivo and in vitro.
  
  
  RESULTS
  Rapamycin significantly attenuated allergic airway inflammation and markedly decreased the amount of eosinophils in local airways, peripheral blood and bone marrow, independently of levels of interleukin-5 (IL-5). In vitro colony forming unit assay and liquid culture demonstrated that rapamycin directly inhibited IL-5-induced eosinophil differentiation. In addition, rapamycin reduced the production of IL-6 and IL-13 by eosinophils. Rapamycin was also capable of reducing the eosinophil levels in IL-5 transgenic NJ.1638 mice, again regardless of the constitutive high levels of IL-5. Interestingly, rapamycin inhibition of eosinophil differentiation in turn resulted in an accumulation of eosinophil lineage-committed progenitors in bone marrow.
  
  
  CONCLUSIONS
  Altogether these results clearly demonstrate a direct inhibitory role of rapamycin in eosinophil differentiation and function, and reemphasize the importance of rapamycin and possibly, mTOR, in allergic airway disease.
authors.affiliation: Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Hua
authors.affiliation: Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
authors.forename: Li-Xia
authors.initials: LX
authors.lastname: Xia
authors.affiliation: Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
authors.forename: Bao-Ping
authors.initials: BP
authors.lastname: Tian
authors.affiliation: Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
authors.forename: Hua-Qiong
authors.initials: HQ
authors.lastname: Huang
authors.affiliation: Institute of Aging Research, Hangzhou Normal University College of Medicine, Hangzhou, Zhejiang, China.
authors.forename: Zhi-Yang
authors.initials: ZY
authors.lastname: Chen
authors.affiliation: Institute of Aging Research, Hangzhou Normal University College of Medicine, Hangzhou, Zhejiang, China.
authors.forename: Zhen-Yu
authors.initials: ZY
authors.lastname: Ju
authors.affiliation: Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
authors.forename: Zhi-Hua
authors.initials: ZH
authors.lastname: Chen
authors.affiliation: Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.|State Key Laboratory of Respiratory Diseases, Guangzhou, Guangdong, China.
authors.forename: Hua-Hao
authors.initials: HH
authors.lastname: Shen
mesh_terms: D000818:Animals; D001249:Asthma / Q000188:drug therapy / Q000276:immunology / Q000473:pathology; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D004195:Disease Models, Animal; D004804:Eosinophils / Q000187:drug effects / Q000276:immunology; D006967:Hypersensitivity / Q000276:immunology; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007249:Inflammation / Q000188:drug therapy / Q000276:immunology / Q000473:pathology; D007378:Interleukins / Q000276:immunology; D007958:Leukocyte Count; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000494:pharmacology; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology; D015398:Signal Transduction; D020123:Sirolimus / Q000494:pharmacology*; D058570:TOR Serine-Threonine Kinases / Q000276:immunology
chemical_list: D007166:Immunosuppressive Agents; D007378:Interleukins; D015842:Serine Proteinase Inhibitors; D010047:Ovalbumin; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus
keywords: allergy; animal model; asthma; eosinophil; inflammation