Plasminogen-induced IL-1beta and TNF-alpha production in microglia is regulated by reactive oxygen species.
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.
Min
Kyoung-jin
KJ
Neuroscience Graduate Program, Ajou University School of Medicine, 442-721, Suwon, South Korea
Jou
Ilo
I
Joe
Eunhye
E
D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005341:Fibrinolysin / Q000378:metabolism* / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D006706:Homeostasis / Q000187:drug effects / Q000502:physiology; D007375:Interleukin-1 / Q000096:biosynthesis*; D051379:Mice; D017628:Microglia / Q000187:drug effects / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000096:biosynthesis*; D052247:Nitric Oxide Synthase Type II; D010958:Plasminogen / Q000378:metabolism* / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
D007375:Interleukin-1; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; D010958:Plasminogen; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; C496318:Nos2 protein, rat; D005341:Fibrinolysin