The Effects of Club Cell Protein 16 on Endothelial NFκB Signaling 2258195

Abstract

Abstract Introduction Club Cell Protein 16 (CC16), one of the most abundant proteins in airway secretions, is primarily produced by Club Cells in the pulmonary epithelium; however, CC16 is readily detectable in circulation. Decreased CC16 concentrations in the serum have been associated with worse lung function in several chronic respiratory diseases, such as COPD and Asthma. CC16 has previously been shown to inhibit PLA2 activity, as well as NFκB activation in airway epithelial cells, yet little is known regarding CC16 interactions with endothelial cells. As such this study aimed to determine if CC16 plays an anti-inflammatory role in endothelial cells. Methods We investigated the effects of rCC16 on canonical NFκB signaling in endothelial cells using hTERT immortalized Human Aortic Endothelial Cells during IL-1β stimulation. Inflammatory factors were assessed by qRT-PCR (IL-6, IL-8, VCAM-1, and ICAM-1) and NFκB signaling pathways were examined by western blot analysis. Results While IL-1β increased all inflammatory factors examined, rCC16 led to significant reductions in both IL-6 and IL-8 when given concurrently during stimulation. Western blot analysis did not display observable trends in phosphorylated P65 at 15 minutes in IL-1β stimulated cells in which rCC16 was present compared to IL-1β stimulation alone. Conclusion These results suggest that CC16 is not merely a serum biomarker of lung function decline but may play an active role in circulation by limiting NFκB -driven inflammation in the endothelium. Further study into the mechanisms by which rCC16 may be effecting endothelial cells is necessary. Funding Source NIH funding: HL142769 Topic Categories Innate Immune Responses and Host Defense: Molecular Mechanisms (INM)