An inverse relationship between peroxisome proliferator-activated receptor gamma and allergic airway inflammation in an allergen challenge model.
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.
Kobayashi
Michiko
M
Respiratory Disease, Wyeth Research, Cambridge, Massachusetts, USA.
Thomassen
Mary Jane
MJ
Rambasek
Todd
T
Bonfield
Tracey L
TL
Raychaudhuri
Baisakhi
B
Malur
Anagha
A
Winkler
Aaron R
AR
Barna
Barbara P
BP
Goldman
Samuel J
SJ
Kavuru
Mani S
MS
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
D000485:Allergens; D047495:PPAR gamma; D012333:RNA, Messenger