CEC01-05 An integrated human-in vitroapproach to explore the role of miRNAs in occupational asthma

Asthma resulting from sensitization of the respiratory tract to chemicals and defined allergic asthma, is associated with significant morbidity, and is clearly an important health concern with serious clinical consequences. Occupational allergic asthma resulting from sensitization of the respiratory tract to chemicals is clearly an important health concern with serious clinical consequences. The main pathological feature of allergic asthma is due to the complex interactions between immune cells and immunological mediators. Basically, Th1/Th2 ratio imbalance is one of the essential immunological mechanisms of asthma but also Th17/Tregs imbalance form an extreme complex interactive network. Recent evidences reported alterations in miRNA expression in a variety of lung diseases, including allergic asthma. Several miRNAs have been associated with asthma and airways inflammation but target identification remain not yet determined for the majority of the studies. Despite research for more than three decades, there are still no validated methods for the assessment of respiratory sensitizing potential of LMW compounds. The main idea of this project is based on the assessment of a new in vitro approach to better study and investigate the allergic asthma pathology. The central hypothesis of this project is that miRNAs play a key role in the activation and maintenance of the allergic asthma through the active involvement of the immune system. The specific aim of this project, that is entirely based on human cells, is to identify miRNA patterns and consequently which specific targets are involved in the interaction between the respiratory system and the immune system in the allergic asthma disease. The project could be ideally divided in two parts: the in vitro part (Part I) and the human part (Part II). Part I – For the in vitro approach the human lung epithelial cells, namely Calu-3, will be exposed to 5 respiratory sensitizers (hexamethylen, methylene diphenyl, and toluene diisocyanate; ammonium hexachloroplatinate; trimellitic anhydride), 1 skin sensitizer (2,4-dinitrochlorobenzene) and 1 irritant (sodium dodecyl sulphate) through a liquid aerosols system (Cloud Alpha System – VITROCELL ® Systems). A microRNA panels will be performed in control conditions and exposed conditions. A bibliographic research will be made to investigate miRNAs possibly involved in allergic asthma and/or immune system activation/de-regulation. Part II – in collaboration with Dott. Liviero (Occupational Unit of Padova University) a broad miRNA evaluation in asthmatic patients will be conducted, through the analysis of miRNA expression in blood microvesicles and in exhaled breath condensate obtained from healthy and asthmatic patients. The translational potential of the project is due to the use of a primary cell culture model as well as human samples. Furthermore, implementation of miRNA patterns could be useful as prevention tool (biomarkers for diagnosis) of allergic asthma.