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. Objectives: 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. Clinical implications: These genes may contribute to the remodeling process that occurs with asthma progression and may have implications for future treatment in severe disease.