Institute of Pharmacology and Toxicology,
University of Zurich;
Swiss Reinsurance Company Ltd.
Inflammatory responses play a fundamental role in the defense against physical injury or infection. Nevertheless, the need to control inflammation is obvious since the pathogenesis of several common diseases is associated with prolonged or inappropriate inflammatory responses ranging from asthma and COPD to cancer, heart disease, and atherosclerosis. In order to harness the body’s own natural ability to down-regulate inflammation, there is a need to identify endogenous anti-inflammatory pathways. Recent findings have shown that adenosine, whose levels are increased during inflammatory and hypoxic processes, plays a crucial role in the down-regulation of inflammation by activating the adenosine receptor A2A. This effect is mediated by transcriptional regulation in key inflammatory cell types, which ultimately results in change of cytokine profiles.
Project 1 deals with the molecular transcriptional events triggered by adenosine on inflammatory cells and how the interplay between the involved signaling pathways can be modulated in the course of an anti-inflammatory response. Understanding these molecular events provoked by adenosine will allow the engineering of specific therapeutic agents for the modulation of inflammatory processes.
In project 2 we complement our cell and molecular research by looking at physiopathological aspects of a commonly occurring disease in horses. Equine recurrent airway obstruction (RAO, previously known as equine COPD) shares many features of human asthma, including lower airway inflammation, reversible airflow obstruction and bronchial hyper-responsiveness. This project aims to establish the role of adenosine signaling in RAO based on the evaluation of bronchoalveolar lavage (BAL) samples from selected RAO-affected horses and to determine if this could represent a novel therapeutic approach for this disease. Three complementary approaches are employed: first, to measure adenosine concentration in BAL samples, second, to assess the status of adenosine receptor subtype expression in tissue sections and in BAL-recovered cells, and third, to evaluate the reactivity of these cells to adenosine receptor stimulation.