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DOI: 10.1055/s-2006-933798
Role of Phosphodiesterases in Idiopathic Pulmonary Fibrosis
Idiopathic pulmonary fibrosis (IPF) is a chronic progressive interstitial lung disease with a fatal outcome. The underlying causes of IPF are currently unknown and there is no available drug therapy that effectively blocks or reverses the progressive scarring of the lung. Drugs which interfere with the cyclic nucleotide levels have profound effects on regulation of airway smooth muscle tone, activation of inflammatory cells, epithelial and smooth muscle cell apoptosis, platelet aggregation, fluid homeostasis. In the present study, we thus intend to investigate the role of the cyclic nucleotide phosphodiesterases (PDEs) in IPF. The large family of PDEs, that catalyse cyclic nucleotide hydrolysis, covers multiple numbers of families, izoenzymes and splice variants. We used a semi-quantitative RT-PCR method to analyse the mRNA expression profile of PDE 1, 2, 3, 4 and 5 families in IPF human lungs compared to healthy donor lungs. The screening revealed significant up-regulation of PDE 1A, PDE 1C and PDE 2A in fibrosis versus donor lungs. These findings indicate that the cAMP/ cGMP-specific PDE 1 and PDE 2 families may play a pivotal role in the cellular signalling mechanisms underlying the pathological entity of IPF and specific inhibition of these PDEs holds promises for therapeutic intervention on lung fibrosis. Supported by DFG, SFB547 „Kardiopulmonales Gefäßsystem“. Sevdalina Nikolova is supported by a predoctoral fellowship from Altana Pharma