1. NSA9, a human prothrombin kringle-2-derived peptide, acts as an inhibitor of kringle-2-induced activation in EOC2 microglia
- Author
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Soung Soo Kim, Jiyeon Kim, and Tae Hyong Kim
- Subjects
MAPK/ERK pathway ,p38 mitogen-activated protein kinases ,Mrna expression ,Drug Evaluation, Preclinical ,Down-Regulation ,Peptide ,Pharmacology ,Nitric Oxide ,Biochemistry ,Cell Line ,Kringles ,Phagocytosis ,medicine ,Humans ,Enzyme Inhibitors ,No production ,Extracellular Signal-Regulated MAP Kinases ,Molecular Biology ,chemistry.chemical_classification ,Dose-Response Relationship, Drug ,Microglia ,Chemistry ,NF-kappa B ,General Medicine ,Peptide Fragments ,Cns injury ,Microglial cell activation ,medicine.anatomical_structure ,Prothrombin - Abstract
In neurodegenerative diseases, such as Alzheimer's and Parkinson's, microglial cell activation is thought to contribute to CNS injury by producing neurotoxic compounds. Prothrombin and kringle-2 increase levels of NO and the mRNA expression of iNOS, IL-1beta, and TNF-alpha in microglial cells. In contrast, the human prothrombin kringle-2 derived peptide NSA9 inhibits NO release and the production of pro-inflammatory cytokines such as IL-1beta, TNF-alpha, and IL-6 in LPS-activated EOC2 microglia. In this study, we investigated the anti-inflammatory effects of NSA9 in human prothrombin- and kringle-2-stimulated EOC2 microglia. Treatment with 20-100 muM of NSA9 attenuated both prothrombin- and kringle-2-induced microglial activation. NO production induced by MAPKs and NF-kappaB was similarly reduced by inhibitors of ERK (PD98059), p38 (SB203580), NF-kappaB (N-acetylcysteine), and NSA9. These results suggest that NSA9 acts independently as an inhibitor of microglial activation and that its effects in EOC2 microglia are not influenced by the presence of kringle-2.
- Published
- 2009
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