title: Porphyromonas gingivalis induces IL-8 and IFN-gamma secretion and apoptosis in human extravillous trophoblast derived HTR8/SVneo cells via activation of ERK1/2 and p38 signaling pathways.
abstract: Preterm birth is a major cause for infant mortality and morbidity. A large number of studies have suggested a link between periodontal disease and preterm birth. The purpose of this study was to investigate the interaction between a periodontopathic bacterium Porphyromonas gingivalis and human extravillous trophoblast derived HTR8/SVneo cells.
  
  
  
  Production of cytokines in HTR8 cells was measured via ELISA. Annexin V/PI flow cytometry was performed to assess apoptosis. Protein expression was measured by western blot. Specific pharmacological inhibitors were used to inactivate relevant signaling pathways (p38 MAPK, SB203580; ERK1/2, U0126; JNK, SP600125; NF-κB, JSH-23) to determine their roles in inflammation and apoptosis.
  
  
  
  HTR8 cells released significant amounts of IL-8 and IFN-γ during exposure to P. gingivalis. Meanwhile, the percentages of both early and late apoptotic cells increased significantly in response to P. gingivalis. The most significant effect on inflammation was found using SB203580 and U0126, followed by SP600125 and JSH-23. Moreover, U0126 and SB203580 both partially but significantly suppressed P. gingivalis-induced apoptosis, with a large effect by U0126. Additionally, both heat-killed P. gingivalis and P. gingivalis lipopolysaccharide significantly induced IL-8 production.
  
  
  
  P. gingivalis induces inflammation and apoptosis in HTR8 cells, and we demonstrated for the first time that activation of ERK1/2 and p38 MAPK pathways participates in P. gingivalis-induced inflammation and apoptosis. The abnormal regulation of inflammation and apoptosis in human trophoblasts by P. gingivalis infection may give new insights into how maternal periodontal disease and periodontal pathogens might be linked to preterm birth.
authors: MOST KLOS & KLOBM, School & Hospital of Stomatology, Wuhan University, Wuhan, Hubei, China.
authors: Hongyu
authors: H
authors: Ren
authors: MOST KLOS & KLOBM, School & Hospital of Stomatology, Wuhan University, Wuhan, Hubei, China.
authors: Yuhong
authors: Y
authors: Li
authors: MOST KLOS & KLOBM, School & Hospital of Stomatology, Wuhan University, Wuhan, Hubei, China.
authors: Han
authors: H
authors: Jiang
authors: MOST KLOS & KLOBM, School & Hospital of Stomatology, Wuhan University, Wuhan, Hubei, China. Electronic address: duminquan@whu.edu.cn.
authors: Minquan
authors: M
authors: Du
mesh_terms: D017304:Annexin A5 / Q000378:metabolism; D017209:Apoptosis / Q000502:physiology*; D002460:Cell Line; D016207:Cytokines / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism*; D016209:Interleukin-8 / Q000378:metabolism*; D016966:Porphyromonas gingivalis; D015398:Signal Transduction / Q000502:physiology*; D014327:Trophoblasts / Q000166:cytology / Q000378:metabolism* / Q000382:microbiology; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D017304:Annexin A5; C508606:CXCL8 protein, human; D016207:Cytokines; D016209:Interleukin-8; D007371:Interferon-gamma; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases
keywords: Apoptosis; Inflammation; MAPK; NF-kappaB; Porphyromonas gingivalis; Trophoblast