Plasminogen-induced IL-1beta and TNF-alpha production in microglia is regulated by reactive oxygen species |
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Authors: | Min Kyoung-jin Jou Ilo Joe Eunhye |
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Institution: | Neuroscience Graduate Program, Ajou University School of Medicine, 442-721, Suwon, South Korea |
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Abstract: | Microglia, major immune effector cells in the central nervous system, become activated during brain injury. In this study we showed that the blood component plasminogen/plasmin activates microglia. Plasminogen-induced IL-1beta, TNF-alpha, and iNOS mRNA expression in primary cultured rat microglia and BV2 murine microglial cells. Plasmin caused a similar response. Serine protease inhibitors suppressed both plasminogen- and plasmin-induced IL-1beta and TNF-alpha expression, indicating the importance of serine protease activity in plasminogen/plasmin activation of microglia. Reactive oxygen species (ROS) appeared to play an important role in plasminogen-induced microglial activation, with ROS being generated within 15min of plasminogen treatment, and antioxidants (100 microM trolox and 10mM NAC) reducing IL-1beta and TNF-alpha expression in plasminogen-treated cells. Furthermore, plasminogen stimulated CREB and NF-kappaB DNA binding activity, and this activation was also reduced by trolox and NAC. These results suggest that plasminogen activates microglia via stimulation of ROS production. |
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Keywords: | Brain inflammation Neurodegenerative disease Signal transduction Microglia Plasminogen Reactive oxygen species Cytokine NF-κB CREB |
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