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Human gene expression profiling for CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD) drug target discovery

 

Chiara Villa,* Michela Mattioli,* Andrea pilucchi,# Antonio Foresi,# Paola Tarroni*

 

* AXXAM s.r.l., via Olgettina 58, 20132 Milan, Italy. # Respiratory Pathophysiology Unit, Sesto San Giovanni Hospital, viale Matteotti 83, 20099 Sesto San Giovanni, Italy

 

Chronic inflammation and exposure to smoke are known to play a key role in COPD pathogenesis. Inflammatory cells signaling pathways hence represent promising targets for innovative COPD therapeutics; studies on human ex vivo cells are of main relevance for gaining pathology knowledge. We have started a program for gene expression profiling of human inflammatory cells from controls/patients and here we report of the pilot study conclusions.

Donor recruitment, following rigorous criteria and patients phenotyping according to GOLD guidelines, was set up to collect blood samples from a) smokers with COPD, b) smokers without COPD, and c) non smokers healthy individuals. Neutrophils, T lymphocytes and monocytes were isolated by immunomagnetic microbeads. We have completed the whole genome expression profiling pilot study on T lymphocytes and monocytes from 15 individuals. We have therefore assessed by statistical methods the number of patients to be analyzed to complete the study and reinforce the preliminary results. Our data indicate that samples show a trend to cluster accordingly to COPD diagnosis and phenotype parameters.  Gene expression levels of inflammation markers, such as IL-8 and TNF-, were verified and a set of differentially expressed genes associated to relevant biological functions related to inflammatory cells activation was identified.

 

 

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