title: Expression of Nodal on Bronchial Epithelial Cells Influenced by Lung Microbes Through DNA Methylation Modulates the Differentiation of T-Helper Cells.
abstract: OBJECTIVE
  The previous study in our lab showed that Nodal molecule on bronchial epithelial cells (BECs) was modulated by all kinds of lung microbes. The present study was designed to determine the effects of Nodal on proliferation of BECs and BECs-induced differentiation of T-helper (Th) cells. The epigenetic mechanisms of Nodal expression following treatments of different lung microbes were also identified.
  
  
  METHODS
  Real-time polymerization chain reaction (PCR) and western blot were used to determine the expression of Nodal. Flow cytometry was used to observe the effects of proliferation of BECs and subsequent BECs-induced differentiation of Th cells. Methylation levels of CpG islands in Nodal promoters were also analyzed by time of flight mass spectrometry.
  
  
  RESULTS
  The results showed that Nodal promoted proliferation of BECs and BECs-induced differentiation of Th cell from Th1 to Th2 and Th17. Nodal promoter showed a hyper-methylation in normal BECs. Through methylation modification in the promoter, P. aeruginosa or A.baumanni inhibited the expression of Nodal while RSV promoted the expression of Nodal.
  
  
  CONCLUSIONS
  Our data showed that Nodal promoted Th2 and Th17 differentiation and inhibited Th1 differentiation which may cause imbalance of airway microenvironment. P. aeruginosa or A.baumanni may be hopeful for the treatment of airway hyperresponsveness by inhibition Nodal expression through DNA methylation modification in the promoter.
authors.forename: Lili
authors.initials: L
authors.lastname: Wang
authors.forename: Guojun
authors.initials: G
authors.lastname: Wu
authors.forename: Xiaoqun
authors.initials: X
authors.lastname: Qin
authors.forename: Qiongshan
authors.initials: Q
authors.lastname: Ma
authors.forename: Yigang
authors.initials: Y
authors.lastname: Zhou
authors.forename: Shuiping
authors.initials: S
authors.lastname: Liu
authors.forename: Yurong
authors.initials: Y
authors.lastname: Tan
mesh_terms: D040981:Acinetobacter baumannii / Q000502:physiology; D001980:Bronchi / Q000166:cytology; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology; D002454:Cell Differentiation; D002460:Cell Line; D018920:Coculture Techniques; D018899:CpG Islands; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D006801:Humans; D055457:Nodal Protein / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D011550:Pseudomonas aeruginosa / Q000502:physiology; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D012136:Respiratory Syncytial Viruses / Q000472:pathogenicity; D021241:Spectrometry, Mass, Electrospray Ionization; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology* / Q000276:immunology / Q000378:metabolism
chemical_list: D055457:Nodal Protein; D034741:RNA, Small Interfering