Cell cycle arrest and apoptosis induced by Porphyromonas gingivalis require Jun N-terminal protein kinase- and p53- mediated p38 activation in human trophoblasts

Hiroaki Inaba, Atsuo Amano, Richard J. Lamont, Yukitaka Murakami, Michiyo Matsumoto-Nakano

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Porphyromonas gingivalis, a periodontal pathogen, has been implicated as a causative agent of preterm delivery of low-birth-weight infants. We previously reported that P. gingivalis activated cellular DNA damage signaling pathways and ERK1/2 that lead to G1 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 P. gingivalis. P. gingivalis infection of HTR-8 cells induced phosphorylation of p38 and Jun N-terminal protein kinase (JNK), while their inhibitors diminished both G1 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 G1 arrest and apoptosis. Furthermore, regulation of G1 arrest and apoptosis was associated with p21 expression. HTR-8 cells infected with P. gingivalis exhibited upregulation of p21, which was regulated by p53 and HSP27. These results suggest that P. gingivalis induces G1 arrest and apoptosis via novel molecular pathways that involve p38 and JNK with its downstream effectors in human trophoblasts.

Original languageEnglish
Article numbere00923-17
JournalInfection and Immunity
Volume86
Issue number4
DOIs
Publication statusPublished - Apr 1 2018
Externally publishedYes

Keywords

  • Apoptosis
  • Cell cycle arrest
  • HSP27
  • JNK
  • P. gingivalis
  • Trophoblast
  • p38

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Infectious Diseases

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