title: Periodontal pathogen Aggregatibacter actinomycetemcomitans LPS induces mitochondria-dependent-apoptosis in human placental trophoblasts.
abstract: OBJECTIVE
  Increasing evidence suggests an association between periodontal disease and low birthweight (LBW); however the underlying molecular mechanisms are yet to be fully elucidated. In this study, we performed a microarray analysis to observe the human placental trophoblast-like BeWo cells response to lipopolysaccharide (LPS) from periodontopathogen Aggregatibacter actinomycetemcomitans (Aa), in order to investigate the molecular basis of mechanisms for periodontitis-associated LBW. In vivo pregnant rats were also used to confirm the in vitro results.
  
  
  METHODS
  The effects of Aa-LPS on cultured human placental trophoblast-like BeWo cells were studied using a DNA microarray, Ingenuity Pathway Analysis, real-time PCR and poly-caspase staining. The in vivo effects of Aa-LPS in pregnant rats were examined using TUNEL assays.
  
  
  RESULTS
  In BeWo cells, Aa-LPS increased levels of cytochrome c, caspase 2, caspase 3, caspase 9 and BCL2-antagonist/killer 1 mRNA, decreased those of B-cell CLL/lymphoma 2, BCL2-like 1 and catalase mRNA and increased poly-caspase activity, all of which are consistent with activation of the mitochondria-dependent apoptotic pathway. TUNEL assays confirmed the increased incidence of apoptosis in placentas of Aa-LPS-treated rats (p < 0.001).
  
  
  CONCLUSIONS
  Aa-LPS induces apoptosis in human trophoblasts via the mitochondria-dependent pathway, and this effect may contribute to the pathogenesis of periodontitis-associated LBW.
authors.affiliation: Department of Biochemistry and Molecular Biology, Nihon University School of Dentistry at Matsudo, 2-870-1, Sakaecho-Nishi, Matsudo, Chiba 271-8587, Japan. yingli3051@263.net
authors.forename: Y
authors.initials: Y
authors.lastname: Li
authors.forename: Y
authors.initials: Y
authors.lastname: Shibata
authors.forename: L
authors.initials: L
authors.lastname: Zhang
authors.forename: N
authors.initials: N
authors.lastname: Kuboyama
authors.forename: Y
authors.initials: Y
authors.lastname: Abiko
mesh_terms: D000189:Actinobacillus Infections / Q000235:genetics / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D016976:Aggregatibacter actinomycetemcomitans / Q000737:chemistry*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D002478:Cells, Cultured; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D008070:Lipopolysaccharides / Q000302:isolation & purification / Q000494:pharmacology*; D046228:Microarray Analysis; D008928:Mitochondria / Q000187:drug effects / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D010518:Periodontitis / Q000235:genetics / Q000378:metabolism / Q000382:microbiology*; D010920:Placenta / Q000166:cytology / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000235:genetics / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014327:Trophoblasts / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology
chemical_list: D008070:Lipopolysaccharides