Department of Pediatric Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan
Department of Preventive Dentistry, Osaka University Graduate School of Dentistry, Suita-Osaka, Japan.
Infect Immun. 2018 Mar 22;86(4). doi: 10.1128/IAI.00923-17. Print 2018 Apr.
, a periodontal pathogen, has been implicated as a causative agent of preterm delivery of low-birth-weight infants. We previously reported that activated cellular DNA damage signaling pathways and ERK1/2 that lead to G arrest and apoptosis in extravillous trophoblast cells (HTR-8 cells) derived from the human placenta. In the present study, we further examined alternative signaling pathways mediating cellular damage caused by infection of HTR-8 cells induced phosphorylation of p38 and Jun N-terminal protein kinase (JNK), while their inhibitors diminished both G arrest and apoptosis. In addition, heat shock protein 27 (HSP27) was phosphorylated through both p38 and JNK, and knockdown of HSP27 with small interfering RNA (siRNA) prevented both G arrest and apoptosis. Furthermore, regulation of G arrest and apoptosis was associated with p21 expression. HTR-8 cells infected with exhibited upregulation of p21, which was regulated by p53 and HSP27. These results suggest that induces G arrest and apoptosis via novel molecular pathways that involve p38 and JNK with its downstream effectors in human trophoblasts.
牙龈卟啉单胞菌是牙周病原体，已被认为是导致早产低体重儿的病原体。我们之前曾报道过，牙龈卟啉单胞菌激活了细胞 DNA 损伤信号通路和 ERK1/2，导致人胎盘绒毛外滋养层细胞（HTR-8 细胞）的 G 期阻滞和细胞凋亡。在本研究中，我们进一步研究了介导 HTR-8 细胞感染引起的细胞损伤的其他信号通路，发现 p38 和 Jun N-末端蛋白激酶（JNK）磷酸化诱导了 G 期阻滞和细胞凋亡，而它们的抑制剂则减少了 G 期阻滞和细胞凋亡。此外，热休克蛋白 27（HSP27）通过 p38 和 JNK 磷酸化，用小干扰 RNA（siRNA）敲低 HSP27 可防止 G 期阻滞和细胞凋亡。此外，G 期阻滞和细胞凋亡的调节与 p21 的表达有关。感染牙龈卟啉单胞菌的 HTR-8 细胞中 p21 的表达上调，这受 p53 和 HSP27 的调节。这些结果表明，牙龈卟啉单胞菌通过涉及 p38 和 JNK 及其在人滋养层细胞中的下游效应物的新分子途径诱导 G 期阻滞和细胞凋亡。
