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Pneumolysin induces cellular senescence in microglial cells: involvement of MAPK and NF‐κB pathways
Author(s) -
Kwon IiSeul,
Pyo Suhkneung
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.1122.2
Subject(s) - pneumolysin , senescence , microbiology and biotechnology , p38 mitogen activated protein kinases , mapk/erk pathway , cell cycle checkpoint , oxidative stress , apoptosis , reactive oxygen species , biology , signal transduction , programmed cell death , cell cycle , streptococcus pneumoniae , genetics , biochemistry , antibiotics
Senescence, which is an irreversible proliferation arrest, is induced by various stress stimuli such as genotoxic stress and oxidative stress. Pneumolysin (Ply) that is important pathogenicity factor unique to S. pneumoniae plays a pathogenic role in pneumococcal‐induced meningitis. Brain cells exposed to PLY undergo cell‐cycle arrest or apoptosis. However, the cell fate response to toxin is mechanistically unclear. In the present study, we investigated the effect of PLY on cellular senescence in BV‐2 microglial cells. Exposure to PLY resulted in changes in the expression of genes associated with senescence and increased senescence‐associated β‐galactosidase (SA‐β‐gal) activity. PLY‐treatment also showed a concentration‐ and time‐dependent increase in PAI‐1 expression and G1/G0 phase arrest. PLY induced NF‐κB activation through the suppression of SIRT‐1 expression and phosphorylation of ERK, JNK and p38 MAP kinase. Additionally, PLY increased the production of reactive oxygen species. Overall, our results suggest that PLY induces cellular senescence by enhancing ROS production, activation of MAPK and NF‐κB, and the inhibition of the SIRT‐1 expression, resulting in regulation of cellular senescence in microglial cells. Senescence, which is an irreversible proliferation arrest, is induced by various stress stimuli such as genotoxic stress and oxidative stress. Pneumolysin (Ply) that is important pathogenicity factor unique to S. pneumoniae plays a pathogenic role in pneumococcal‐induced meningitis. Brain cells exposed to PLY undergo cell‐cycle arrest or apoptosis. However, the cell fate response to toxin is mechanistically unclear. In the present study, we investigated the effect of PLY on cellular senescence in BV‐2 microglial cells. Exposure to PLY resulted in changes in the expression of genes associated with senescence and increased senescence‐associated β‐galactosidase (SA‐β‐gal) activity. PLY‐treatment also showed a concentration‐ and time‐dependent increase in PAI‐1 expression and G1/G0 phase arrest. PLY induced NF‐κB activation through the suppression of SIRT‐1 expression and phosphorylation of ERK, JNK and p38 MAP kinase. Additionally, PLY increased the production of reactive oxygen species. Overall, our results suggest that PLY induces cellular senescence by enhancing ROS production, activation of MAPK and NF‐κB, and the inhibition of the SIRT‐1 expression, resulting in regulation of cellular senescence in microglial cells.