title: Differential expression of peroxisome proliferator activated receptor gamma and cyclin D1 does not affect proliferation of asthma- and non-asthma-derived airway smooth muscle cells.
abstract: PPARgamma levels in asthma- and non-asthma-derived airway smooth muscle cells and PPARgamma activation-induced cell proliferation were investigated. In the presence of FBS, PPARgamma levels were higher in subconfluent asthma-derived cells but lower in confluent cells compared with non-asthma-derived. However, PPARgamma activation did not alter cell proliferation.
  
  
  OBJECTIVE
  Airway remodelling involves thickening of the airway smooth muscle (ASM) bulk. Proliferation of asthma-derived ASM cells is increased in vitro, but underlying mechanisms remain unknown. Peroxisome proliferators activated receptor-gamma (PPARgamma) regulates the cell cycle. It is suggested that PPARgamma agonists have anti-inflammatory effects, which may be valuable in the treatment of asthma, but information regarding their antiproliferative properties in ASM is lacking. Although corticosteroids reduce airway inflammation, in vitro they inhibit proliferation in only non-asthma ASM cells by reducing cyclin D1. We therefore investigated the effects of mitogenic stimulation (foetal bovine serum (FBS)), and a PPARgamma ligand (ciglitazone), on PPARgamma and cyclin D1 expression and proliferation of ASM cells. In addition, we examined the effects of ciglitazone on ASM cell proliferation.
  
  
  METHODS
  We assessed PPARgamma and cyclin D1 mRNA and protein levels using quantitative PCR and immunoblotting. Cell proliferation was assessed using bromodeoxyuridine uptake.
  
  
  RESULTS
  In the presence of 5% FBS, PPARgamma and cyclin D1 expression decreased over time in non-asthmatic cells but increased in asthmatic cells (compared with sub-confluent cells). FBS-induced proliferation of asthmatic cells increased at all time points, but occurred only at day 7 with non-asthmatic cells (compared with unstimulated time-matched control). Ciglitazone increased PPARgamma expression in both groups, but did not alter cell proliferation, while fluticasone increased PPARgamma protein only in asthmatic cells.
  
  
  CONCLUSIONS
  Although in the presence of a mitogenic stimulus, PPARgamma was differentially expressed in asthma- and non-asthma-derived ASM; its expression was not related to the increased proliferation observed in asthmatic ASM.
authors.affiliation: Cooperative Research Centre for Asthma and Airways, The University of Sydney, Sydney, New South Wales, Australia. jlau@med.usyd.edu.au
authors.forename: Justine Y
authors.initials: JY
authors.lastname: Lau
authors.forename: Brian G
authors.initials: BG
authors.lastname: Oliver
authors.forename: Lyn M
authors.initials: LM
authors.lastname: Moir
authors.forename: Judith L
authors.initials: JL
authors.lastname: Black
authors.forename: Janette K
authors.initials: JK
authors.lastname: Burgess
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000730:Androstadienes / Q000494:pharmacology; D001249:Asthma / Q000378:metabolism* / Q000473:pathology*; D001980:Bronchi / Q000473:pathology; D001993:Bronchodilator Agents / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D019938:Cyclin D1 / Q000378:metabolism*; D005260:Female; D000068298:Fluticasone; D006801:Humans; D008297:Male; D008875:Middle Aged; D008934:Mitogens / Q000494:pharmacology; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D047495:PPAR gamma / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D045162:Thiazolidinediones / Q000494:pharmacology; D055815:Young Adult
chemical_list: D000730:Androstadienes; D001993:Bronchodilator Agents; D008934:Mitogens; D047495:PPAR gamma; D012333:RNA, Messenger; D045162:Thiazolidinediones; D019938:Cyclin D1; D000068298:Fluticasone; C039671:ciglitazone