Study on the influence of diesel particulate matter on the processes of metabolism, differentiation and cell growth in co-culture of respiratory epithelial cells and THP-1 inflammatory cells.

• Grant number: 24/00343-0
• Support Opportunities: Scholarships in Brazil - Master
• Start date: August 01, 2024
• End date: July 31, 2025
• Field of knowledge: Biological Sciences - Pharmacology - Toxicology
• Principal Investigator: Mariangela Macchione
• Grantee: Gabriela Lima Vieira
• Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Exposure to air pollution is a growing global concern, given its association witha variety of adverse impacts on human health. The interaction between lungepithelial cells, immune system cells, and air pollutants, such as dieselparticulate matter (DEP), triggers a cascade of molecular events that cancompromise normal cellular function and lead to adverse health consequences.These effects include activation of inflammatory pathways, oxidative stress,DNA damage, and even tumor promotion. Understanding these mechanisms isessential to develop strategies to prevent and mitigate damage caused by airpollution, protecting the population's lung and immunological health. Polycyclicaromatic hydrocarbons (PAHs) trigger the activation of the aryl hydrocarbonreceptor (AhR), responsible for regulating the enzymes of the xenobioticmetabolizing system (CYP450) and the transcription factor Nrf2, playing acrucial role in the basal activation of antioxidant enzymes . AhR plays amultifaceted role in cellular responses, affecting both antioxidant regulation,acting on the indirect activation of Nrf2, and cell cycle regulation (Ccno cyclin).To investigate changes in cellular mechanisms, especially related to theproduction of cytokines (TNF-±, and IL-6) and the architecture of the cellularcytoskeleton (cytokeratin), Nrf2 silencing and AhR knockout will be performedusing the CRISPR/Cas9 technique. in normal (BEAS-2B) and cancerous (A549)epithelial cells, in co-culture conditions, separately, to THP-1 cells, differentiatedinto macrophages, exposed to DEP. Thus, it is possible to develop a cellularmicroenvironment suitable for analyzing the pathophysiological conditions ofcell behavior when exposed to DEP.