Increased expression of ADAM33 and ADAM8 with disease progression in asthma.
BACKGROUND
ADAM33, a disintegrin and metalloproteinase 33 gene, has been identified as a risk factor for asthma and bronchial hyperresponsiveness and has been postulated as a gene for airway remodeling. ADAM8 is strongly induced by allergens and T(H)2 cytokines in the lung in experimental asthma.


OBJECTIVE
To assess the importance of these genes in asthma pathogenesis and to investigate whether expression relates to disease severity or deterioration in lung function, we measured the mRNA and protein expression of both genes in bronchial biopsies of subjects with asthma and control subjects.


METHODS
RNA was extracted from frozen endobronchial biopsies of mild, moderate, and severe adults with asthma and controls. Subjects with moderate and severe asthma were taking corticosteroids. The mRNA transcript of both genes was measured by real time RT-PCR using specific primers. Protein expression was examined by immunohistochemistry on paraffin sections.


RESULTS
ADAM33 mRNA expression was significantly higher in both moderate and severe asthma compared with mild asthma (P < .05) and controls. Immunostaining for ADAM33 was increased in the epithelium, submucosal cells, and smooth muscle in severe asthma compared with mild disease and controls. ADAM8 mRNA expression was significantly increased in all asthma groups compared with controls. Increased inflammatory cells stained positive for ADAM8 in both moderate (P < .05) and severe asthma (P < .005) compared with mild disease.


CONCLUSIONS
These results demonstrate increased expression of both ADAM genes as asthma severity increases.


CONCLUSIONS
These genes may contribute to the remodeling process that occurs with asthma progression and may have implications for future treatment in severe disease.
Foley
Susan C
SC
Meakins-Christie Laboratories, McGill University, Montreal Chest Institute, Montréal, Québec, Canada.
Mogas
Andrea K
AK
Olivenstein
Ron
R
Fiset
Pierre O
PO
Chakir
Jamila
J
Bourbeau
Jean
J
Ernst
Pierre
P
Lemière
Catherine
C
Martin
James G
JG
Hamid
Qutayba
Q
D051722:ADAM Proteins / Q000096:biosynthesis / Q000235:genetics*; D000328:Adult; D001249:Asthma / Q000209:etiology / Q000378:metabolism*; D002478:Cells, Cultured; D018450:Disease Progression; D005260:Female; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000096:biosynthesis / Q000235:genetics*; D008875:Middle Aged
D008565:Membrane Proteins; D051722:ADAM Proteins; C450441:ADAM33 protein, human; C068490:ADAM8 protein, human