title: Plasminogen-induced IL-1beta and TNF-alpha production in microglia is regulated by reactive oxygen species.
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.
authors.affiliation: Neuroscience Graduate Program, Ajou University School of Medicine, 442-721, Suwon, South Korea
authors.forename: Kyoung-jin
authors.initials: KJ
authors.lastname: Min
authors.forename: Ilo
authors.initials: I
authors.lastname: Jou
authors.forename: Eunhye
authors.initials: E
authors.lastname: Joe
mesh_terms: 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*
chemical_list: 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