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

被引：64

作者：

Min, KJ

Jou, I

Joe, E ^{[1
]}

机构：

[1] Ajou Univ, Sch Med, Grad Program Neurosci, Suwon 442721, South Korea

[2] Ajou Univ, Sch Med, Dept Pharmacol, Suwon 442721, South Korea

[3] Ajou Univ, Sch Med, Brain Dis Res Ctr, Suwon 442721, South Korea

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2003年 / 312卷 / 04期

关键词：

brain inflammation; neurodegenerative disease; signal transduction; microglia; plasminogen; reactive oxygen species; cytokine; NF-kappa B; CREB;

D O I：

10.1016/j.bbrc.2003.11.010

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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 15 min of plasminogen treatment, and antioxidants (100 muM trolox and 10 mM 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. (C) 2003 Elsevier Inc. All rights reserved.

引用

页码：969 / 974

页数：6

共 48 条

[1] Redox regulation of cAMP-responsive element-binding protein and induction of manganous superoxide dismutase in nerve growth factor-dependent cell survival [J].