Jin Zhenyu, Tsuruya Yuto, Igarashi Kazuma, Yamaguchi Arisa, Takai Hideki, Nakayama Yohei, Ogata Yorimasa
Department of Periodontology, Nihon University School of Dentistry at Matsudo, Chiba, Japan.
Research Institute of Oral Science, Nihon University School of Dentistry at Matsudo, Chiba, Japan.
Odontology. 2025 Jan 8. doi: 10.1007/s10266-024-01050-9.
Follicular dendritic cell-secreted protein (FDC-SP) is produced by follicular dendritic cells, periodontal ligament and junctional epithelium (JE). JE exists immediately apical to the bottom of the pocket and binds enamel with hemidesmosomes to protect the periodontium from bacterial infection. To analyze the transcriptional regulation of the FDC-SP gene by interleukin-6 (IL-6), we performed real-time PCR, Western blotting, immunofluorescence, luciferase (LUC) assays, gel mobility shift and chromatin immunoprecipitation (ChIP) assays using Ca9-22 and Sa3 gingival epithelial cells. IL-6 increased FDC-SP mRNA and protein levels at 3-24 h. IL-6 increased LUC activities of the LUC constructs containing FDC-SP gene promoter sequences from -116 to -717 bp upstream from the transcriptional start site. IL-6 induced LUC activities of -345FDCSP were inhibited by protein kinase A, tyrosine kinase, mitogen-activated protein kinase kinase, phosphoinositide 3-kinase, signal transducer, activator of transcription 3 (STAT3) and glycoprotein 130 inhibitors. Gel shift and ChIP assays showed that IL-6 induced Yin Yang1 (YY1), GATA binding protein (GATA), CCAAT/enhancer-binding protein (C/EBP) β, phosphorylated STAT3 (p-STAT3) binding to YY1, GATA, C/EBP2, C/EBP3 and GAS2-3 elements. These results indicate that IL-6 induces FDC-SP gene transcription YY1, GATA, C/EBP2, GAS2-3 and C/EBP3 elements in the human FDC-SP gene promoter, and suggesting that FDC-SP may be involved in the defense against JE in periodontium during the progression of periodontitis.
滤泡树突状细胞分泌蛋白（FDC-SP）由滤泡树突状细胞、牙周韧带和结合上皮（JE）产生。结合上皮紧邻牙周袋底部的根尖部，通过半桥粒与牙釉质结合，以保护牙周组织免受细菌感染。为了分析白细胞介素-6（IL-6）对FDC-SP基因的转录调控，我们使用Ca9-22和Sa3牙龈上皮细胞进行了实时聚合酶链反应、蛋白质免疫印迹、免疫荧光、荧光素酶（LUC）检测、凝胶迁移率变动分析和染色质免疫沉淀（ChIP）检测。IL-6在3至24小时内增加了FDC-SP的信使核糖核酸和蛋白质水平。IL-6增加了含有转录起始位点上游-116至-717碱基对的FDC-SP基因启动子序列的LUC构建体的荧光素酶活性。蛋白激酶A、酪氨酸激酶、丝裂原活化蛋白激酶激酶、磷脂酰肌醇3激酶、信号转导子、转录激活因子3（STAT3）和糖蛋白130抑制剂抑制了IL-6诱导的-345FDCSP的荧光素酶活性。凝胶迁移率变动分析和ChIP检测表明，IL-6诱导阴阳1（YY1）、GATA结合蛋白（GATA）、CCAAT/增强子结合蛋白（C/EBP）β、磷酸化STAT3（p-STAT3）与YY1、GATA、C/EBP2、C/EBP3和GAS2-3元件结合。这些结果表明，IL-6在人类FDC-SP基因启动子中通过YY1、GATA、C/EBP2、GAS2-3和C/EBP3元件诱导FDC-SP基因转录，提示FDC-SP可能在牙周炎进展过程中参与牙周组织结合上皮的防御。
