Uemura Yuta, Hiroshima Yuka, Tada Ayano, Murakami Keiji, Yoshida Kaya, Inagaki Yuji, Kuwahara Tomomi, Murakami Akikazu, Fujii Hideki, Yumoto Hiromichi
Department of Periodontology and Endodontology, Graduate School of Biomedical Sciences, Tokushima University, 3-18-15 Kuramoto, Tokushima 770-8504, Japan.
Department of Oral Microbiology, Graduate School of Biomedical Sciences, Tokushima University, 3-18-15 Kuramoto, Tokushima 770-8504, Japan.
Biomedicines. 2022 Oct 20;10(10):2643. doi: 10.3390/biomedicines10102643.
() is a keystone pathogen associated with chronic periodontitis and produces outer membrane vesicles (OMVs) that contain lipopolysaccharide (LPS), gingipains, and pathogen-derived DNA and RNA. -OMVs are involved in the pathogenesis of periodontitis. -OMV-activated pathways that induce the production of the pro-inflammatory cytokines, interleukin (IL)-6, and IL-8 in the human gingival epithelial cell line, OBA-9, were investigated. The role of mitogen-activated protein kinase (MAPK) and nuclear factor (NF)-κB in levels of -OMV-induced pro-inflammatory cytokines was investigated using Western blot analysis and specific pathway inhibitors. -OMVs induced IL-6 and IL-8 production via the extracellular signal-regulated kinase (Erk) 1/2, c-Jun N-terminal kinase (JNK), p38 MAPK, and NF-κB signaling pathways in OBA-9 cells. In addition, the stimulator of interferon genes (STING), an essential innate immune signaling molecule, was triggered by a cytosolic pathogen DNA. -OMV-induced IL-6 and IL-8 mRNA expression and production were significantly suppressed by STING-specific small interfering RNA. Taken together, these results demonstrated that -OMV-activated Erk1/2, JNK, p38 MAPK, STING, and NF-κB signaling pathways resulting in increased IL-6 and IL-8 expression in human gingival epithelial cells. These results suggest that -OMVs may play important roles in periodontitis exacerbation by stimulating various pathways.
（）是与慢性牙周炎相关的关键病原体，可产生包含脂多糖（LPS）、牙龈蛋白酶以及病原体来源的DNA和RNA的外膜囊泡（OMV）。-OMV参与牙周炎的发病机制。-研究了OMV激活的诱导人牙龈上皮细胞系OBA-9中促炎细胞因子白细胞介素（IL）-6和IL-8产生的途径。使用蛋白质印迹分析和特定途径抑制剂研究了丝裂原活化蛋白激酶（MAPK）和核因子（NF）-κB在-OMV诱导的促炎细胞因子水平中的作用。-OMV通过细胞外信号调节激酶（Erk）1/2、c-Jun氨基末端激酶（JNK）、p38 MAPK和NF-κB信号通路在OBA-9细胞中诱导IL-6和IL-8的产生。此外，干扰素基因刺激物（STING）是一种重要的先天免疫信号分子，由胞质病原体DNA触发。-STING特异性小干扰RNA显著抑制了OMV诱导的IL-6和IL-8 mRNA表达及产生。综上所述，这些结果表明-OMV激活的Erk1/2、JNK、p38 MAPK、STING和NF-κB信号通路导致人牙龈上皮细胞中IL-6和IL-8表达增加。这些结果表明-OMV可能通过刺激各种途径在牙周炎加重中发挥重要作用。
