Enhanced pulmonary leptin expression in patients with severe COPD and asymptomatic smokers.

J.H. Vernooy, N.E. Drummen, R.J. van Suylen, R.H. Cloots, G.M. Moller, K.R. Bracke, S. Zuyderduyn, M.A. Dentener, G.G. Brusselle, P.S. Hiemstra, E.F. Wouters

    Research output: Contribution to journalArticleAcademicpeer-review

    Abstract

    BACKGROUND: COPD is characterized by an abnormal inflammatory reaction of the lungs, involving activation of epithelial cells. Leptin is a pleiotropic cytokine important in the regulation of immune responses via its functional receptor Ob-Rb. This study was undertaken to test the hypothesis that severe COPD is associated with increased leptin expression in epithelial cells. METHODS: Immunohistochemistry for leptin was performed on peripheral lung specimens from 20 COPD patients (GOLD 4), 14 asymptomatic (ex-)smokers and 13 never smokers. Leptin and Ob-Rb mRNA expression was determined by rtPCR in cultured primary bronchial epithelial cells (BEC) and primary type II pneumocytes. NCI-H292 and A549 cell lines were used to study functional activation of leptin signalling. RESULTS: Leptin immunoreactivity in lung tissue was observed in BEC, type II pneumocytes, macrophages (tissue/alveolar), and interstitial lymphocytic infiltrates. rtPCR analysis confirmed pulmonary leptin and Ob-Rb mRNA expression in primary BEC and pneumocytes. Leptin-expressing BEC and alveolar macrophages were markedly higher in severe COPD patients and (ex-) smokers versus never smokers (p<0.02). Exposure of cultured primary BEC to smoke resulted in increased expression of both leptin and Ob-Rb (p<0.05). Leptin induced phosphorylation of STAT3 in both NCI-H292 and A549 cells. CONCLUSIONS: Leptin expression is increased in BEC and alveolar macrophages of (ex-) smokers with or without severe COPD versus never smokers. A functional leptin signalling pathway is present in lung epithelial cells.
    Original languageEnglish
    Pages (from-to)26-32
    JournalThorax
    Volume64
    Issue number1
    DOIs
    Publication statusPublished - 1 Jan 2009

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