Bone Morphogenic Proteins and their antagonists in the lower airways of stable COPD patients

Abstract

<b>Background:</b> Bone morphogenic proteins (BMPs) and their antagonists are involved in development and homeostasis in various organs. <b>Objective:</b> To determine the protein expression of BMPs and their antagonists in stable COPD. <b>Methods:</b> The expression and localization of BMPs and some relevant antagonists was measured in bronchial biopsies (bb) of patients with stable COPD with mild/moderate (n=18), severe/very severe disease (n=16), control smokers (CS)(n=13) and control non-smokers (CNS)(n=11) and in lung parenchyma of mild/moderate COPD (n=9), CS (n=11) and CNS (n=9) using immunohistochemistry and transcriptome analysis. <b>Results:</b> In large airways (bb) the BMP4 antagonists CRIM1 and Chordin were significantly increased in bronchial epithelium and in the lamina propria of COPD. BMPER was slightly increased in the bronchial epithelium of all smokers, with or without COPD, compared to control non-smokers. BMP4 expression was decreased in the bronchial epithelium of severe-very severe and mild-moderate COPD compared to control non-smokers. Chordin levels (cells/mm2) in bb significantly inversely correlated with FEV1% predicted values in patients with COPD. In vitro stimulation of 16HBE epithelial cells with RANTES and IL-8 (100ng/ml) induced a significant decrease in BMP4 over 0-24h. In the peripheral airways BMP8a protein increased significantly in bronchiolar epithelium and lamina propria of COPD patients compared to both control groups. Transcriptome data were similar in all groups studied. <b>Conclusion:</b> These data show an imbalance of BMPs proteins and their antagonists in the bronchial mucosa of stable COPD.