Presentation description

Individuals plagued by chronic inflammation of the lungs often suffer from respiratory diseases, such as CF. Although advancements in targeted CFTR protein therapy have been made, a subset of the CF community is left with an untreatable form of the disease. Understanding how epithelial sodium channels (ENaCs) cause electrochemical imbalances that lead to chronic inflammation opens the possibility of universal treatment for lung inflammation and diseases such as cystic fibrosis (CF). Derived from our preliminary findings, we hypothesize that hyperactive ENaC dysfunction distorts cellular osmolarity, leading to extracellular release of HMGB1 and its association with RAGE, thereby driving innate immune responses following increased ENaC activity.

To support this new line of inquiry, we measured osmotic stress observed in A549 lung epithelial cells in different osmolarities of PBS. Measurements of cells in 344 mOsm, 170 mOsm, 170 mOsm + 1uM amiloride, and 170 mOsm NMDG were made. Cell volume changes were quantified using ImageJ software, and SigmaPlot 14.0 was utilized for statistical analysis to determine whether sodium ions (Na+) are a crucial regulator of cell size. Additionally, extracellular HMGB1 and RAGE in primary cells and bronchoalveolar lavage fluid (BALF) isolated from WT and Scnn1b (lung ENaC overexpression) mouse models were directly measured.