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Prothrombin kringle-2 activates cultured rat brain microglia.

Ryu, J; Min, KJ; Rhim, TY; Kim, TH; Pyo, H; Jin, B; Kim, SU; Jou, I; Kim, SS; Joe, EH
Journal of immunology (Baltimore, Md. : 1950), 168(11):5805-5810, 2002
Journal Title
Journal of immunology (Baltimore, Md. : 1950)
Microglia, the major immune effector cells in the CNS, become activated when the brain suffers injury. In this study, we observed that prothrombin, a zymogen of thrombin, induced NO release and mRNA expression of inducible NO synthase, IL-1beta, and TNF-alpha in rat brain microglia. The effect of prothrombin was independent of the protease activity of thrombin since hirudin, a specific inhibitor of thrombin, did not inhibit prothrombin-induced NO release. Furthermore, factor Xa enhanced the effect of prothrombin on microglial NO release. Kringle-2, a domain of prothrombin distinct from thrombin, mimicked the effect of prothrombin in inducing NO release and mRNA expression of inducible NO synthase, IL-1beta, and TNF-alpha. Prothrombin and kringle-2 both triggered the same intracellular signaling pathways. They both activated mitogen-activated protein kinases and NF-kappaB in a similar pattern. NO release stimulated by either was similarly reduced by inhibitors of the extracellular signal-regulated kinase pathway (PD98059), p38 (SB203580), NF-kappaB (N-acetylcysteine), protein kinase C (Go6976, bisindolylmaleimide, and Ro31-8220), and phospholipase C (D609 and U73122). These results suggest that prothrombin can activate microglia, and that, in addition to thrombin, kringle-2 is a domain of prothrombin independently capable of activating microglia.
MeSH terms
AnimalsBrain/*drug effects/metabolismCells, CulturedEnzyme ActivationFactor Xa/pharmacologyInterleukin-1/geneticsKringles/*physiologyMicroglia/*drug effects/metabolismMitogen-Activated Protein Kinases/metabolismNF-kappa B/metabolismNitric Oxide/biosynthesisNitric Oxide Synthase/geneticsNitric Oxide Synthase Type IIProtein Kinase C/physiologyProthrombin/*pharmacologyRNA, Messenger/analysisRatsRats, Sprague-DawleyTumor Necrosis Factor-alpha/geneticsType C Phospholipases/physiology
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Journal Papers > School of Medicine / Graduate School of Medicine > Pharmacology
AJOU Authors
조, 은혜
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