Microglial responses after phagocytosis: Escherichia coli bioparticles, but not cell debris or amyloid beta, induce matrix metalloproteinase-9 secretion in cultured rat primary microglial cells

Gen Hamanaka, Tomoya Kubo, Ryo Ohtomo, Hajime Takase, Estefania Reyes-Bricio, Shuntaro Oribe, Noriko Osumi, Josephine Lok, Eng H. Lo, Ken Arai

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

Upon infection or brain damage, microglia are activated to play roles in immune responses, including phagocytosis and soluble factor release. However, little is known whether the event of phagocytosis could be a trigger for releasing soluble factors from microglia. In this study, we tested if microglia secrete a neurovascular mediator matrix metalloproteinase-9 (MMP-9) after phagocytosis in vitro. Primary microglial cultures were prepared from neonatal rat brains. Cultured microglia phagocytosed Escherichia coli bioparticles within 2 hr after incubation and started to secrete MMP-9 at around 12 hr after the phagocytosis. A TLR4 inhibitor TAK242 suppressed the E. coli-bioparticle-induced MMP-9 secretion. However, TAK242 did not change the engulfment of E. coli bioparticles in microglial cultures. Because lipopolysaccharides (LPS), the major component of the outer membrane of E. coli, also induced MMP-9 secretion in a dose–response manner and because the response was inhibited by TAK242 treatment, we assumed that the LPS-TLR4 pathway, which was activated by adhering to the substance, but not through the engulfing process of phagocytosis, would play a role in releasing MMP-9 from microglia after E. coli bioparticle treatment. To support the finding that the engulfing step would not be a critical trigger for MMP-9 secretion after the event of phagocytosis in microglia, we confirmed that cell debris and amyloid beta were both captured into microglia via phagocytosis, but neither of them induced MMP-9 secretion from microglia. Taken together, these data demonstrate that microglial response in MMP-9 secretion after phagocytosis differs depending on the types of particles/substances that microglia encountered.

Original languageEnglish
Pages (from-to)1435-1444
Number of pages10
JournalGlia
Volume68
Issue number7
DOIs
Publication statusPublished - 2020 Jul 1

Keywords

  • Escherichia coli
  • amyloid beta
  • cell debris
  • matrix metalloproteinase-9
  • microglia
  • phagocytosis

ASJC Scopus subject areas

  • Neurology
  • Cellular and Molecular Neuroscience

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