Crosstalk between Akt and NF-κB pathway mediates inhibitory effect of gas6 on monocytes-endothelial cells interactions stimulated by P. gingivalis-LPS.

Correlation between periodontitis and atherosclerosis is well established, and the inherent mechanisms responsible for this relationship remain unclear. The biological function of growth arrest-specific 6 (gas6) has been discovered in both atherosclerosis and inflammation. Inhibitory effects of gas6 on the expression of inflammatory factors in human umbilical vein endothelial cells (HUVECs) stimulated by Porphyromonas gingivalis lipopolysaccharide (P. gingivalis-LPS) were reported in our previous research. Herein, the effects of gas6 on monocytes-endothelial cells interactions in vitro and their probable mechanisms were further investigated. Gas6 protein in HUVECs was knocked down with siRNA or overexpressed with plasmids. Transwell inserts and co-culturing system were introduced to observe chemotaxis and adhering affinity between monocytes and endothelial cells in vitro. Expression of gas6 was decreased in inflammatory periodontal tissues and HUVECs challenged with P. gingivalis-LPS. The inhibitory effect of gas6 on chemotaxis and adhesion affinity between monocytes and endothelial cells was observed, and gas6 promoted Akt phosphorylation and inhibited NF-κB phosphorylation. To our best knowledge, we are first to report that gas6 inhibit monocytes-endothelial cells interactions in vitro induced by P. gingivalis-LPS via Akt/NF-κB pathway. Additionally, inflammation-mediated inhibition of gas6 expression is through LncRNA GAS6-AS2, rather than GAS6-AS1, which is also newly reported.