title: Neuronal injury induces cytokine-induced neutrophil chemoattractant-1 (CINC-1) production in astrocytes.
abstract: Accumulating evidence indicates a pivotal role for neuroinflammation in ischemic and excitotoxic brain injury. Cytokine-induced neutrophil chemoattractant-1 (CINC-1) is a CXC chemokine implicated in the infiltration of inflammatory cells into the brain parenchyma. In this study, we investigated the effect of N-methyl-D-aspartate (NMDA)-induced neuronal injury on CINC-1 production in the organotypic cortico-striatal slice cultures. Treatment with 50 microM NMDA for 3 - 4 h caused devastating neuronal damage and increased CINC-1 production. Immunohistochemical analysis revealed that the CINC-1 immunoreactivity was predominantly detected in astrocytes. NMDA failed to induce CINC-1 production in enriched astrocyte cultures or neuron-depleted slice cultures, suggesting that NMDA acted on neuronal cells to induce astrocytic CINC-1 production. NMDA-induced CINC-1 mRNA expression was significantly inhibited by U0126, a mitogen-activated protein kinase/extracellular signal-regulated kinase (ERK) kinase (MEK) inhibitor. These results suggest that NMDA-evoked neuronal injury induced astrocytic CINC-1 production via a MEK/ERK signaling pathway. Manipulation of this signaling pathway may serve as a target for suppressing neuroinflammation and, thereby, treating ischemic brain injury.
authors.affiliation: Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Katayama
authors.forename: Hiroki
authors.initials: H
authors.lastname: Tanaka
authors.forename: Tadashi
authors.initials: T
authors.lastname: Yoshida
authors.forename: Takashi
authors.initials: T
authors.lastname: Uehara
authors.forename: Masabumi
authors.initials: M
authors.lastname: Minami
mesh_terms: D000818:Animals; D000873:Anthracenes / Q000494:pharmacology; D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D002070:Butadienes / Q000494:pharmacology; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000473:pathology; D054360:Chemokine CXCL1 / Q000235:genetics / Q000378:metabolism*; D003342:Corpus Striatum / Q000473:pathology; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D007093:Imidazoles / Q000494:pharmacology; D007120:Immunochemistry; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D016202:N-Methylaspartate / Q000633:toxicity; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D009570:Nitriles / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors
chemical_list: D000873:Anthracenes; D002070:Butadienes; D054360:Chemokine CXCL1; C513297:Cxcl1 protein, rat; D004791:Enzyme Inhibitors; D007093:Imidazoles; D009570:Nitriles; D011725:Pyridines; D012333:RNA, Messenger; C113580:U 0126; C432165:pyrazolanthrone; D016202:N-Methylaspartate; D016291:Dizocilpine Maleate; D020928:Mitogen-Activated Protein Kinases; C093642:SB 203580