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Crosstalk between Akt and NF-κB pathway mediates inhibitory effect of gas6 on monocytes-endothelial cells interactions stimulated by P. gingivalis-LPS.
Journal of Cellular and Molecular Medicine ( IF 5.3 ) Pub Date : 2020-05-28 , DOI: 10.1111/jcmm.15430
Xuekui Wang 1, 2, 3, 4, 5 , Yingjun Liu 1, 3, 4, 5 , Shengnan Zhang 2, 3, 4, 5 , Xiangying Ouyang 2, 3, 4, 5 , Yuguang Wang 3, 4, 5 , Yong Jiang 1, 3, 4, 5 , Na An 1, 3, 4, 5
Affiliation  

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.

中文翻译:

Akt和NF-κB通路之间的串扰介导gas6对牙龈卟啉单胞菌-LPS刺激的单核细胞-内皮细胞相互作用的抑制作用。

牙周炎与动脉粥样硬化之间的相关性已被很好地建立,并且导致这种关系的内在机制仍不清楚。在动脉粥样硬化和炎症中都发现了特定于生长停滞的6(gas6)的生物学功能。gas6对牙龈卟啉单胞菌脂多糖(P. gingivalis)刺激的人脐静脉内皮细胞(HUVEC)中炎性因子表达的抑制作用-LPS)在我们以前的研究中已有报道。本文进一步研究了gas6对体外单核细胞-内皮细胞相互作用的影响及其可能的机制。HUVEC中的Gas6蛋白用siRNA敲低或用质粒过表达。引入Transwell插入物和共培养系统以观察体外单核细胞和内皮细胞之间的趋化性和粘附亲和力。在牙周炎攻击的牙周炎组织和HUVEC中gas6的表达降低‐LPS。观察到gas6对趋化性和单核细胞与内皮细胞之间的粘附亲和力有抑制作用,gas6促进Akt磷酸化并抑制NF-κB磷酸化。据我们所知,我们是第一个报道gas6通过Akt /NF-κB途径体外抑制齿龈丙酸杆菌-LPS诱导的单核细胞-内皮细胞相互作用的研究。此外,炎症介导的gas6表达抑制是通过LncRNA GAS6-AS2而非GAS6-AS1进行的,这也是最近报道的。
更新日期:2020-07-10
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