Modern societies face an increasing impact of environmental, including air, pollution. Lung health is especially affected. Pollution induced changes accumulate over time and cause development of various diseases locally, systemically and affect healthy aging. It is proven that air pollutants, tobacco smoke and pathogens cause post?translational modification of the proteins, including citrullination, leading to the production of autoantibodies and possible systemic autoimmune response. Reports show that citrullinated proteins and deiminases are more prevalent in patients with COPD and that smoking correlates with increased deiminase levels. This is explained by smoking?induced inflammation and oxidative stress rather that smoking per se. Other posible causal mechanisms are also studied. Such assays are performed on lung tissue explants or lung tissue models in vitro. Tissue sample collection from smokers, non?smokers, COPD patients, urban and rural population volunteers would be highly appreciated. We will assess citrullination in the human and mouse lung tissues, identify indicators and relevant pathogenesis factors for the entire group of aging?related diseases, like COPD, lung cancer, macular degeneration, neurodegenerative diseases, atherosclerosis etc. Toxic effects will be investigated in vitro: in alveolar epithelium, microvascular endothelium, bronchial epithelium, lung fibroblasts, where primary pollution effects are exerted. We will also investigate in vivo citrullination, its systemic effects and distribution of modified proteins within the mouse body under exposure to air pollution and cigarette smoke. Human material will also be tested (we already have collected an initial collection of lung tissue explants). Next, protective effects of novel inhibitors of citrullination and similar processes will be evaluated. Phytocannabinoids, their derivates and synergistic mixes will be employed for that.
Research Council of Lithuania (RCL), National Research Programme “Healthy Ageing”
Data obtained in our study will enable to select appropriate dietary and therapeutic interventions for maintaining lung health and healthy aging. Novel indicators of citrullination will allow tailored selection and monitoring of the treatment strategies, will help identify common processes across disease group(s) and will enable development of the novel effective management and prevention strategies.
Period of project implementation: 2016-10-01 - 2018-09-30
Project coordinator: Centre for Innovative Medicine
Project partners: Kaunas University of Technology