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Plasminogen-induced IL-1beta and TNF-alpha production in microglia is regulated by reactive oxygen species

Kyoung-jin Min1, Ilo Jou, Eunhye Joe

  • 1Neuroscience Graduate Program, Ajou University School of Medicine, 442-721, Suwon, South Korea

Biochemical and Biophysical Research Communications
|December 4, 2003
PubMed

Insights

The blood component plasminogen activates brain immune cells called microglia. This activation involves serine protease activity and reactive oxygen species (ROS), suggesting a new pathway for brain injury responses.

Area of Science:

  • Neuroimmunology
  • Molecular Biology
  • Cellular Biology

Background:

  • Microglia are key immune cells in the central nervous system.
  • Microglial activation is a hallmark of brain injury.
  • The specific triggers for microglial activation during injury are not fully understood.

Purpose of the Study:

  • To investigate the role of the blood component plasminogen/plasmin in microglial activation.
  • To elucidate the molecular mechanisms underlying plasminogen-induced microglial activation.

Main Methods:

  • Primary cultured rat microglia and BV2 murine microglial cells were used.
  • Gene expression (IL-1beta, TNF-alpha, iNOS mRNA) was measured.
  • Serine protease inhibitors and antioxidants (trolox, NAC) were employed.
  • DNA binding activity of transcription factors (CREB, NF-kappaB) was assessed.

Main Results:

  • Plasminogen and plasmin induced the expression of inflammatory markers (IL-1beta, TNF-alpha, iNOS) in microglia.
  • Serine protease activity was essential for this induction.
  • Reactive oxygen species (ROS) generation was observed rapidly after plasminogen treatment.
  • Antioxidants significantly reduced inflammatory gene expression and transcription factor activation.
  • Plasminogen stimulated CREB and NF-kappaB DNA binding activity.

Conclusions:

  • Plasminogen activates microglia, a critical step in brain injury responses.
  • This activation is mediated by serine protease activity and subsequent ROS production.
  • Plasminogen's action on microglia involves the transcription factors CREB and NF-kappaB.

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