Increased cerebrospinal fluid osteopontin levels and its involvement in macrophage infiltration in neuromyelitis optica

Yoshinobu Kariya, Yukiko Kariya, Toshie Saito, Shuhei Nishiyama, Takashi Honda, Keiko Tanaka, Mari Yoshida, Kazuo Fujihara, Yasuhiro Hashimoto

Research output: Contribution to journalArticlepeer-review

8 Citations (Scopus)

Abstract

Background: Neuromyelitis optica (NMO) is an inflammatory disease of the central nervous system that predominantly affects the optic nerves and spinal cord. Although NMO has long been considered a subtype of multiple sclerosis (MS), the effects of interferon-b treatment are different between NMO and MS. Recent findings of NMO-IgG suggest that NMO could be a distinct disease rather than a subtype of MS. However, the underlying molecular mechanism of NMO pathology remains poorly understood. Methods: OPN in the cerebrospinal fluid and brain of patients with NMO and with MS, as well as of patients with other neurologic disease/idiopathic other neurologic disease was examined using Western blotting, ELISA, immunohistochemistry and Boyden chamber. Results: Here we show that osteopontin is significantly increased in the cerebrospinal fluid of NMO patients compared with MS patients. Immunohistochemical analyses revealed that osteopontin was markedly elevated in the cerebral white matter of NMO patients and produced by astrocytes, neurons, and oligodendroglia as well as infiltrating macrophages. We also demonstrate that the interaction of the cerebrospinal fluid osteopontin in NMO patients with integrin avb3 promoted macrophage chemotaxis by activating phosphoinositide 3-kinase and MEK1/2 signaling pathways. Conclusion: These results indicate that osteopontin is involved in NMO pathology. General significance: Thus therapeutic strategies that target osteopontin signaling may be useful to treat NMO.

Original languageEnglish
Pages (from-to)126-134
Number of pages9
JournalBBA Clinical
Volume3
DOIs
Publication statusPublished - 2015 Jun 1

Keywords

  • Biomarker
  • Cerebrospinal fluid
  • Integrin
  • Multiple sclerosis
  • Neuromyelitis optica
  • Osteopontin

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Molecular Medicine
  • Physiology (medical)

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