Changes in proteome activity and chemokine expression patterns in airway epithelial cells induced by particulate matter

Exposure to particulate matter (PM) from ambient air has been shown to be a considerable health problem. Accumulating evidence suggests that inflammation plays an important role in the development of respiratory health effects associated with PM-exposure. The airway epithelium plays an active role in mediating pulmonary inflammation. Epithelium-derived chemokines are crucial to recruit immune cells to the site of injury. Depending on the chemokine pattern the innate or adaptive (Th1/Th2) immune system wil l be activated. Thus, revealing the mechanism regulating PM-induced chemokine release from epithelial cells may be important to understand the pathology of lung diseases associated with PM exposure. In the presented project we will expose airway epithel ial cells to ambient PM and PM components such as PAHs, ultrafine particles, mineral particles and metals. Reactive oxygen species will also be included in the study. We aim to characterise changes in chemokine expression pattern induced by PM and PM comp onents, and how this is associated with changes in proteomal activity (i.e. changes in protein expression or protein phosphorylation). We will identify component-specific intracellular signals and investigate their involvement in PM-induced chemokine rele ase. We also aim to characterise how component-induced stress signals are organised and regulated in intracellular pathways. The work will be performed in cooperation with Ken Donaldson, Edinburgh, Scotland, and ongoing projects at the Department of Air P ollution and Noise, NIPH. The project will provide important information on how PM induces inflammatory reactions in the pulmonary epithelium, how different constituents of PM contribute in these responses, and how different PM components may react in co ncert to the observed effect of PM-exposure. Understanding the ability of different PM components to induce inflammatory reactions may contribute towards developing a more refined PM metric for risk assessment.