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

Abstract

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.

Suppression of lncRNA GAS6-AS2 alleviates sepsis-related acute kidney injury through regulating the miR-136-5p/OXSR1 axis in vitro and in vivo

“…Here, GAS6-AS2 expression was found to be abnormally up-regulated in HK2 cells treated with LPS and renal tissues from sepsis AKI rats, which was consistent with previous results. Additionally, GAS6-AS2 is associated with the apoptosis of melanoma cells [ 14 ], hepatocellular carcinoma cells [ 10 ], and osteosarcoma cells [ 12 ], as well as inflammation [ 15 ]. We found that down-regulation of GAS6-AS2 could significantly relieve apoptosis, inflammatory response, and oxidative stress in renal epithelial cells, as well as reduce kidney pathology in AKI rats.…”

“…LncRNA GAS6-AS2 has been shown to act as an oncogene to promote the development of a number of tumors, such as hepatocellular carcinoma [ 10 ], breast cancer [ 11 ], osteosarcoma [ 12 ], non-small-cell lung cancer [ 9 ], bladder cancer [ 13 ], and melanoma [ 14 ]. In addition, existing results indicated that GAS6-AS2 was related to inflammatory response [ 15 ] and apoptosis [ 14 ], which are also the important features of septic AKI. However, the role and mechanism of GAS6-AS2 in sepsis-related AKI are unknown.…”

Gas6/TAM Signalling Negatively Regulates Inflammatory Induction of GM-CSF in Mouse Brain Microglia

“…We observed a strong increase in levels of p65 in the nuclei of microglia exposed to LPS, which was markedly reduced when cells were co-incubated with Gas6. Gas6 has previously been shown to attenuate neuroinflammation through inhibition of the NF-κB family in damaged brain tissue [ 52 ] and both the Mer and Axl receptors have been shown to be involved in the Gas6-mediated response [ 53 ]. Here, we have expanded the known associations by demonstrating that Gas6 alters GM-CSF signalling through modification of the NF-κB pathway.…”

STAT1/SOCS1/3 Are Involved in the Inflammation-Regulating Effect of GAS6/AXL in Periodontal Ligament Cells Induced by Porphyromonas gingivalis Lipopolysaccharide In Vitro

“…AXL originates from hematopoietic, epithelial, and mesenchymal cells and is expressed in most human cells [ 7 ], whereas GAS6 is widely expressed in a variety of tissues such as the bone, lung, heart, and kidney, but its expression level is low in the liver [ 37 ]. P. gingivalis LPS inhibits the expression of AXL and GAS6 in human umbilical vein endothelial cells [ 38 ]. The inhibitory effect of Escherichia coli LPS on the expression of AXL in human umbilical vein endothelial cells has also been reported [ 39 ].…”