title: An inverse relationship between peroxisome proliferator-activated receptor gamma and allergic airway inflammation in an allergen challenge model.
abstract: BACKGROUND
  Peroxisome proliferator-activated receptor gamma (PPAR-gamma) expression has not been evaluated in bronchoalveolar lavage (BAL) cells from allergic asthmatic patients.
  
  
  OBJECTIVE
  To determine whether inappropriate down-regulation of PPAR-gamma in alveolar macrophages may contribute to persistent airway inflammation in allergic asthma.
  
  
  METHODS
  We used segmental allergen challenge as a model of in vivo experimental allergic asthmatic exacerbation and airway inflammation. PPAR-y gene expression was evaluated at baseline and 24 hours later in asthmatic patients and controls using real-time polymerase chain reaction. Immunofluorescence was used to determine cellular location of the PPAR-gamma protein.
  
  
  RESULTS
  We demonstrate for the first time to our knowledge that PPAR-gamma messenger RNA and protein, which are highly expressed in alveolar macrophages of healthy individuals, are significantly reduced in asthmatic patients after segmental allergen challenge. In allergic asthmatic patients (n=9), PPAR-gamma gene expression decreased significantly from baseline to postchallenge BAL (median decrease, 45%; P = .008). Furthermore, immunofluorescence staining demonstrated that PPAR-gamma protein was associated with alveolar macrophages and not with inflammatory eosinophils and neutrophils.
  
  
  CONCLUSIONS
  Results implicate down-regulation of PPAR-gamma in BAL cells as a potential factor in dysregulation of lung homeostasis in asthmatic patients. The present findings suggest that PPAR-gamma agonists could have a future role in asthma therapy and warrant further study.
authors.affiliation: Respiratory Disease, Wyeth Research, Cambridge, Massachusetts, USA.
authors.forename: Michiko
authors.initials: M
authors.lastname: Kobayashi
authors.forename: Mary Jane
authors.initials: MJ
authors.lastname: Thomassen
authors.forename: Todd
authors.initials: T
authors.lastname: Rambasek
authors.forename: Tracey L
authors.initials: TL
authors.lastname: Bonfield
authors.forename: Baisakhi
authors.initials: B
authors.lastname: Raychaudhuri
authors.forename: Anagha
authors.initials: A
authors.lastname: Malur
authors.forename: Aaron R
authors.initials: AR
authors.lastname: Winkler
authors.forename: Barbara P
authors.initials: BP
authors.lastname: Barna
authors.forename: Samuel J
authors.initials: SJ
authors.lastname: Goldman
authors.forename: Mani S
authors.initials: MS
authors.lastname: Kavuru
mesh_terms: D000293:Adolescent; D000328:Adult; D000402:Airway Obstruction / Q000276:immunology* / Q000378:metabolism; D000485:Allergens / Q000276:immunology*; D001249:Asthma / Q000276:immunology* / Q000378:metabolism; D001985:Bronchial Provocation Tests; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D015536:Down-Regulation; D015870:Gene Expression; D006801:Humans; D007249:Inflammation / Q000276:immunology* / Q000378:metabolism; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000276:immunology*; D008875:Middle Aged; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis
chemical_list: D000485:Allergens; D047495:PPAR gamma; D012333:RNA, Messenger