title: PI3K and Notch signal pathways coordinately regulate the activation and proliferation of T lymphocytes in asthma.
abstract: OBJECTIVE
  In the present study, we determined whether Phosphoinositide 3-kinase (PI3K) and Notch signal pathways are involved in the expression of cyclinD1, cyclinA and p27kip1 which were key molecules in controlling cell cycling from CD4(+) T lymphocyte in animal model of asthma.
  
  
  METHODS
  Ovalbumin (OVA) sensitized murine model of asthma was used to investigate the expression of cyclin D1, cyclin A, and p27kip1 by splenic CD4(+) T lymphocytes. We further observed the effect of specific inhibitor of PI3K(LY294002) and specific inhibitor of Notch(DAPT) on the proliferation of such CD4(+) T lymphocytes.
  
  
  RESULTS
  We found that the expression of cyclinD1 and cyclinA was upregulated at both protein and mRNA levels in asthma group while p27kip1 was down-regulated. Both LY294002 and DAPT inhibit the proliferation of CD4(+) T lymphocytes in a time- and dose-dependent manner. Furthermore, LY294002 and DAPT have additive effect in down-regulation of cyclinD1 and upregulation of p27kip1. An upregulation of cyclinA, although not statistically significant, was also observed.
  
  
  CONCLUSIONS
  These data suggested that PI3K signal pathway and Notch signal pathway may coordinately regulate the cell proliferation and differentiation processes through up-regulating cyclinD1 and down-regulating p27kip1 of CD4(+) T lymphocytes.
authors.affiliation: Department of Pediatric Pulmonology, The Second Affiliated Hospital &Yuying Children's Hospital, Wenzhou Medical College, Wenzhou 325027, China.
authors.forename: Weixi
authors.initials: W
authors.lastname: Zhang
authors.forename: Ying
authors.initials: Y
authors.lastname: Nie
authors.forename: Lei
authors.initials: L
authors.lastname: Chong
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Cai
authors.forename: Hui
authors.initials: H
authors.lastname: Zhang
authors.forename: Beibei
authors.initials: B
authors.lastname: Lin
authors.forename: Yafeng
authors.initials: Y
authors.lastname: Liang
authors.forename: Changchong
authors.initials: C
authors.lastname: Li
mesh_terms: D000818:Animals; D001249:Asthma / Q000378:metabolism*; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000378:metabolism*; D049109:Cell Proliferation / Q000187:drug effects; D002867:Chromones / Q000008:administration & dosage / Q000494:pharmacology; D019925:Cyclin A / Q000235:genetics; D019938:Cyclin D1 / Q000235:genetics; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000235:genetics; D004151:Dipeptides / Q000008:administration & dosage / Q000494:pharmacology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009025:Morpholines / Q000008:administration & dosage / Q000494:pharmacology; D010047:Ovalbumin; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D012333:RNA, Messenger / Q000378:metabolism; D051880:Receptors, Notch / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013154:Spleen / Q000166:cytology / Q000378:metabolism; D013997:Time Factors; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D002867:Chromones; D019925:Cyclin A; D019938:Cyclin D1; D050760:Cyclin-Dependent Kinase Inhibitor p27; D004151:Dipeptides; D009025:Morpholines; D010047:Ovalbumin; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D012333:RNA, Messenger; D051880:Receptors, Notch; C530105:Ccnd1 protein, mouse; C493961:Cdkn1b protein, mouse; C419410:N-(N-(3,5-difluorophenacetyl)alanyl)phenylglycine tert-butyl ester; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one