title: Anti-inflammatory effect of a human prothrombin fragment-2-derived peptide, NSA9, in EOC2 microglia.
abstract: Pro-inflammatory mediators, such as nitric oxide (NO), prostaglandin E(2) (PGE(2)), and several cytokines (tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, and IL-6) are responsible for central nervous system (CNS) injuries that include ischemia, Alzheimer's disease, and neural death. Inhibition of these pro-inflammatory mediators would be an effective therapy to reduce the progression of neurodegenerative diseases. In this study, we examined the anti-inflammatory effects of a human prothrombin fragment-2-derived peptide, NSA9 (NSAVQLVEN), on the production of pro-inflammatory mediators in lipopolysaccharide (LPS)-activated brain microglia. NSA9 significantly inhibited the release of NO, PGE(2), and pro-inflammatory cytokines in a dose-dependent manner. Furthermore, NSA9 reduced the expression of inducible NO synthase (iNOS) and cyclooxygenase (COX)-2 mRNA and protein, which control the production of NO and PGE(2), respectively. Moreover, NSA9 suppressed the LPS-induced nuclear translocation and activation of nuclear factor-kappaB (NF-kappaB). These results suggest that NSA9 strongly inhibits the pro-inflammatory responses of microglia through the modulation of NF-kappaB activity.
authors.affiliation: Department of Biochemistry, College of Science, Yonsei University, 134, Sinchon-dong, Seodaemun-gu, Seoul 120-749, Republic of Korea.
authors.forename: Ji Yeon
authors.initials: JY
authors.lastname: Kim
authors.forename: Tae Hyong
authors.initials: TH
authors.lastname: Kim
authors.forename: Soung Soo
authors.initials: SS
authors.lastname: Kim
mesh_terms: D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D006801:Humans; D018836:Inflammation Mediators / Q000276:immunology*; D017628:Microglia / Q000187:drug effects / Q000276:immunology*; D010446:Peptide Fragments / Q000008:administration & dosage*; D011516:Prothrombin / Q000008:administration & dosage*; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology*
chemical_list: D018836:Inflammation Mediators; D010446:Peptide Fragments; C044183:prothrombin fragment 2; D011516:Prothrombin