title: Pathological Involvement of Astrocyte-Derived Lipocalin-2 in the Demyelinating Optic Neuritis.
abstract: OBJECTIVE
  The current study was done to determine the role of lipocalin-2 (LCN2) in the pathogenesis of demyelinating optic neuritis using an experimental autoimmune optic neuritis (EAON) model.
  
  
  METHODS
  The EAON was induced by subcutaneous immunization with an emulsified mixture of myelin oligodendrocyte glycoprotein (MOG35-55) peptide in mice. The LCN2 expression was examined in the optic nerve after MOG peptide injection. Degree of demyelination, inflammatory infiltration, glial activation, and expression profile of inflammatory mediators in the optic nerve were compared between LCN2 knockout (KO) animals and wild-type littermates by histological analysis and real-time PCR following EAON induction. Plasma levels of LCN2 in patients with optic neuritis were measured by ELISA.
  
  
  RESULTS
  The expression of LCN2 was notably increased in the optic nerve after EAON induction. Expression of LCN2 was colocalized with reactive astrocytes. A significant reduction of demyelination, inflammatory infiltration, and gliosis was demonstrated in the optic nerve of LCN2 KO mice. The LCN2 KO mice also showed markedly reduced gene expression associated with the M1-polarized glia phenotype and toll-like receptor signaling in the optic nerve. The LCN2 levels in plasma were significantly higher in optic neuritis patients (71.6 ± 10.6 ng/mL) compared to healthy controls (37.4 ± 9.1 ng/mL, P = 0.0284).
  
  
  CONCLUSIONS
  In this study, we demonstrated a significant induction of LCN2 expression in astrocytes of the optic nerve following EAON induction. Our results imply that astrocyte-derived LCN2 may have a pivotal role in the development of demyelinating optic neuritis, and LCN2 can be a therapeutic target to alleviate immune and inflammatory damage in the optic nerve.
authors.affiliation: Department of Ophthalmology Kyungpook National University School of Medicine, Daegu, Korea.
authors.forename: Bo Young
authors.initials: BY
authors.lastname: Chun
authors.affiliation: Department of Pharmacology, Brain Science and Engineering Institute, and Department of Biomedical Sciences, BK21 Plus KNU Biomedical Convergence Program, Kyungpook National University School of Medicine, Daegu, Korea.
authors.forename: Jong-Heon
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Department of Pharmacology, Brain Science and Engineering Institute, and Department of Biomedical Sciences, BK21 Plus KNU Biomedical Convergence Program, Kyungpook National University School of Medicine, Daegu, Korea.
authors.forename: Youngpyo
authors.initials: Y
authors.lastname: Nam
authors.affiliation: Biomedical Research Institute, Kyungpook National University Hospital, Daegu, Korea.
authors.forename: Man-Il
authors.initials: MI
authors.lastname: Huh
authors.affiliation: Division of Rheumatology, Department of Internal Medicine, Daegu Fatima Hospital, Daegu, Korea.
authors.forename: Seungwoo
authors.initials: S
authors.lastname: Han
authors.affiliation: Department of Pharmacology, Brain Science and Engineering Institute, and Department of Biomedical Sciences, BK21 Plus KNU Biomedical Convergence Program, Kyungpook National University School of Medicine, Daegu, Korea.
authors.forename: Kyoungho
authors.initials: K
authors.lastname: Suk
mesh_terms: D000209:Acute-Phase Proteins / Q000096:biosynthesis / Q000502:physiology*; D000328:Adult; D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D003711:Demyelinating Diseases / Q000097:blood / Q000209:etiology*; D005260:Female; D006801:Humans; D000071068:Lipocalin-2; D054834:Lipocalins / Q000096:biosynthesis / Q000097:blood / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009902:Optic Neuritis / Q000097:blood / Q000209:etiology*; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000097:blood / Q000502:physiology*
chemical_list: D000209:Acute-Phase Proteins; C489506:LCN2 protein, human; D000071068:Lipocalin-2; D054834:Lipocalins; D011518:Proto-Oncogene Proteins