PhD defence I. (Isabella) Cattani Pinto Cavalieri
|When:||Mo 14-06-2021 18:00 - 19:00|
Air pollution exposure of lung models
Focus on inflammation, oxidative stress and cAMP signaling
Air pollution is a global public health concern and represents one of the main environmental risk factors for mortality associated with unwanted respiratory events.
A growing body of evidence indicates that air pollution promotes the induction of inflammation and oxidative stress in the lungs. Conversely, intracellular signaling associated with (an increase in) the second messenger cAMP is known to reduce and/or protect against airway inflammation, oxidative stress and mitochondrial dysfunction. Interestingly, a relationship between mitochondrial dysfunction (as an underlying pathological mechanism) and several chronic diseases, including COPD and asthma, has been proposed.
Air pollution contains considerable amounts of particulate matter (PM), including diesel exhaust particles (DEP) that contain highly toxic compounds. We evaluated the effects of DEP and biodiesel PM on lung (patho)physiology in vitro (e.g., by using human bronchial epithelial cells) and in vivo in mouse models of acute and chronic air pollution exposure. The studies described in this thesis show that exposure to these air pollutants promotes airway inflammation, oxidative stress and epithelial-to-mesenchymal transition. In addition, exposure to DEP induced mitochondrial dysfunction and changes in the cellular ability to produce cAMP. We speculate that mitochondrial cAMP nanodomains are critical in disrupting cAMP homeostasis. From a more clinically relevant perspective, our studies identify and highlight the therapeutic potential of dimethyl fumarate (DMF) to reduce DEP-induced parameters of airway inflammation, oxidative/nitrosative stress, and overall lung injury. The exact mechanisms by which DMF affects the inflammatory response and antioxidant system will be the topic of future research by our group.
Promotores: prof. dr. M. Schmidt and prof.dr. S. dos Santos Valenca