Expression profiling of chemotactic receptors in inflammatory diseases

Inflammatory diseases, such as Inflammatory Bowel Disease (IBD), Chronic Obstructive Pulmonary Disease (COPD) and rheumatoid arthritis, are associated with a significant accumulation of leukocytes in the respective tissues. Chemokines and their receptors are key mediators involved in the infiltration of leukocytes. Chemokine receptors belong to the class of G protein coupled receptors (GPCRs) and are therefore considered important drug targets for treatment of inflammatory diseases. In addition, also other chemotactic GPCRs, like the histamine H4and C5aR1 receptors, were found to be expressed on subsets of leukocytes. We have established a quantitative PCR array to define the expression levels of the different chemotactic receptors in patient (e.g. IBD) and control material. Validation of expression of the chemotactic receptors is performed by Western blot analysis, immunohistochemistry and/or binding studies. For example, we have shown histamine H4expression with immunohistochemistry on both inflamed and non-inflamed tissue of IBD patients. This approach is a first step to define novel targets in inflammatory diseases.