Department of Periodontology, Peking University School and Hospital of Stomatology, Beijing 100081, China.
Department of General Dentistry II, Peking University School and Hospital of Stomatology, Beijing 100081, China.
J Immunol Res. 2021 Oct 25;2021:9577695. doi: 10.1155/2021/9577695. eCollection 2021.
Periodontitis involves chronic inflammation of the tissues around the teeth caused by plaque and the corresponding immune response. Growth arrest-specific protein 6 (GAS6) and AXL receptor tyrosine kinase (AXL) are known to be involved in inflammatory diseases, while signal transducer and activator of transcription-1 (STAT1) and suppressor of cytokine signaling (SOCS) are related to inflammatory processes. Moreover, miRNA34a directly targets to regulate the AXL expression. However, the specific roles of GAS6 and AXL in periodontitis remain unclear. This study was designed to explore the effect and mechanism of AXL on the expression of inflammatory cytokines induced by lipopolysaccharide ( LPS) in human periodontal ligament cells (hPDLCs). The effects of different concentrations of LPS on the expression of GAS6/AXL in hPDLCs were observed. Additionally, the effect of LPS on AXL was investigated by transfection of the miRNA34a inhibitor. was knocked down or overexpressed to observe the release of inflammatory cytokines interleukin- (IL-) 8 and IL-6. The results showed that the expression levels of GAS6 and AXL decreased after LPS infection. Transfection of a miR-34a inhibitor to hPDLCs demonstrated a role of miR-34a in the downregulation of AXL expression induced by LPS. Moreover, knockdown or overexpression influencing the expression of IL-8 and IL-6 was investigated under LPS stimulation. knockdown decreased the expression of STAT1 and SOCS1/3. Overall, these results demonstrate that AXL inhibits the expression of LPS-induced inflammatory cytokines in hPDLCs and that STAT1 and SOCS1/3 are involved in the regulation of inflammation by GAS6/AXL.
牙周炎涉及由斑块引起的牙齿周围组织的慢性炎症和相应的免疫反应。生长停滞特异性蛋白 6（GAS6）和 AXL 受体酪氨酸激酶（AXL）已知参与炎症性疾病，而信号转导和转录激活因子 1（STAT1）和细胞因子信号转导抑制因子（SOCS）与炎症过程有关。此外，miRNA34a 可直接靶向 以调节 AXL 的表达。然而，GAS6 和 AXL 在牙周炎中的具体作用尚不清楚。本研究旨在探讨 AXL 在脂多糖（LPS）诱导的人牙周膜细胞（hPDLCs）炎症因子表达中的作用及其机制。观察不同浓度 LPS 对 hPDLCs 中 GAS6/AXL 表达的影响。此外，通过转染 miRNA34a 抑制剂研究 LPS 对 AXL 的影响。敲低或过表达 观察炎症因子白细胞介素-（IL-）8 和 IL-6 的释放。结果表明，LPS 感染后 GAS6 和 AXL 的表达水平降低。miR-34a 抑制剂转染 hPDLCs 表明 miR-34a 在 LPS 诱导的 AXL 表达下调中起作用。此外，还研究了 LPS 刺激下 敲低或过表达对 IL-8 和 IL-6 表达的影响。 敲低降低了 STAT1 和 SOCS1/3 的表达。总体而言，这些结果表明 AXL 抑制 LPS 诱导的 hPDLCs 中炎症因子的表达，并且 STAT1 和 SOCS1/3 参与 GAS6/AXL 对炎症的调节。
