Akos HEINEMANN
Devision of Pharmacology
Otto Loewi Research Center
Medical University of Graz
Neue Stiftingstalstraße 6
A-8010 Graz
Website Heinemann group
Program
”Prostaglandins in lung fibrosis and asthma”
Idiopathic pulmonary fibrosis (IPF) and bronchial asthma (BA) are chronic progressive disorders of unknown origin with limited therapeutic options. IPF progresses with the recruitment of fibroblasts and myofibroblasts that contribute to the accumulation of extracellular matrix (ECM) proteins, leading to the loss of compliance and alveolar integrity, compromising the gas exchange capacity of the lung. BA asthma is an inflammatory disease of the airways that is characterized by periodic or sustained airway narrowing, and in severe cases by exacerbations needing hospitalization. In the majority of asthma patients elevated levels of eosinophil granulocytes can be found in the lungs and blood.
Of the known prostanoid receptors, human eosinophils express the prostaglandin D2 (PGD2) receptors DP1 [also D-type prostanoid (DP)] and DP2, the prostaglandin E2 receptors EP2 and EP4, and the prostacyclin (PGI2) receptor IP. Prostanoids can bind to either one or multiple receptors, characteristically have a short half-life in vivo, and are quickly degraded into metabolites with altered affinity and specificity for a given receptor subtype. Prostanoid receptors signal mainly through G proteins and naturally activate signal transduction pathways according to the G protein subtype that they preferentially interact with. This can lead to the activation of sometimes opposing signaling pathways. In addition, prostanoid signaling is often cell-type specific and also the combination of expressed receptors can influence the outcome of the prostanoid impulse. The major prostaglandin PGE2 is known to exert protective effects in BA, and shows antifibrotic properties in IPF. Thus, the aim of this talk is to give an overview of prostaglandin pharmacology in respiratory diseases.
Host: Johannes SCHMID
Contact for questions: Helmut KUBISTA