Gas6 protein induces invasion and reduces inflammatory cytokines in oral squamous cell carcinoma

Hirschi, Kelsey M.; Chapman, Steven; Hall, Parker; Ostergar, Adam; Winden, Duane R.; Reynolds, Paul; Arroyo, Juan A.

doi:10.1111/jop.12738

Cited by 3 publications

(3 citation statements)

References 29 publications

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“…Accordingly, monocyte chemotaxis and adhesion were mitigated by gas6. Previous studies [26][27][28][29] showed that several aspects of gas6/TAM systems are involved in orchestrating inflammation, including the attenuation of inflammatory lung injury and sepsis-induced tight junction injury. Congruent with our findings, gas6 was also reported to inhibit the adhesion of polymorphonuclear cells to endothelial cells in a dose-dependent manner, 30 and not only inhibit VCAM-1 expression in human microvascular endothelial cells induced by high glucose, 31 but inhibit NF-κB activation in mouse aortic endothelial cells induced by E. coli LPS.…”

Section: Discussionmentioning

confidence: 99%

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

Wang

Liu

Zhang

et al. 2020

J Cellular Molecular Medi

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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.

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Section: Discussionmentioning

confidence: 99%

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

Wang

Liu

Zhang

et al. 2020

J Cellular Molecular Medi

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“…We next wanted to determine lung-signaling molecules in this model of PE. Specifically, we studied levels of ERK and AKT kinases that signal transduction and are activated in Gas6/AXL signaling [ 8 , 20 ]. A characteristic Western blot for ERK and AKT is shown in Figure 4 A,C.…”

Section: Resultsmentioning

confidence: 99%

“…The activation of these signaling molecules was decreased to basal levels when the AXL inhibitor was added to the treated animals ( Figure 4 B,D). Because increased infiltration of cells in the lungs was observed in Gas6 treatment and that previous studies have shown a correlation between ERT and AKT proteins and the modulation of inflammation, we decided to determine levels of secreted lung-associated inflammatory cytokines in this model of PE [ 20 , 21 , 22 ]. Interleukin 1 alpha (IL-1α) is a pro-inflammatory cytokine that is known to be increased during damage to the epithelium of the lung and has been suggested as a driver of inflammation in disease [ 23 ].…”

Section: Resultsmentioning

confidence: 99%

Lung Inflammation Is Associated with Preeclampsia Development in the Rat

Curtis

Clarke

Hanegan

et al. 2022

Cells

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Preeclampsia (PE) is an obstetric complication associated with significant health implications for the fetus and mother. Studies have shown a correlation between lung disease development and PE. Gas6 protein is expressed in the lung and placenta, and binds to the AXL Tyrosine kinase receptor. Recently, our laboratory utilized Gas6 to induce preeclamptic-like conditions in rats. Our objective was to determine the role of Gas6/AXL signaling in the maternal lung during PE development. Briefly, pregnant rats were divided into control, Gas6, or Gas6 + R428 (an AXL inhibitor). Immunofluorescence was performed to determine AXL expression. Bronchoalveolar lavage fluid (BALF) was procured for the assessment of inflammatory cell secretion. Western blot was performed to detect signaling molecules and ELISA determined inflammatory cytokines. We observed increased proteinuria and increased blood pressure in Gas6-treated animals. AXL was increased in the lungs of the treated animals and BALF fluid revealed elevated total protein abundance in Gas6 animals. Extracellular-signal regulated kinase (ERK) and protein kinase B (AKT) signaling in the lung appeared to be mediated by Gas6 as well as the secretion of inflammatory cytokines. We conclude that Gas6 signaling is capable of inducing PE and that this is associated with increased lung inflammation.

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