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Osteopontin expression in the brain triggers localized inflammation and cell death when immune cells are activated by pertussis toxin

Academic Article
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Overview

authors

  • Marcondes, Maria Cecilia
  • Ojakian, R.
  • Bortell, N.
  • Flynn, C.
  • Conti, Bruno
  • Fox, H. S.

publication date

  • 2014

journal

  • Mediators of Inflammation  Journal

abstract

  • Upregulation of osteopontin (OPN) is a characteristic of central nervous system pathologies. However, the role of OPN in inflammation is still controversial, since it can both prevent cell death and induce the migration of potentially damaging inflammatory cells. To understand the role of OPN in inflammation and cell survival, we expressed OPN, utilizing an adenoviral vector, in the caudoputamen of mice deficient in OPN, using beta-galactosidase- (?-gal-) expressing vector as control. The tissue pathology and the expression of proinflammatory genes were compared in both treatments. Interestingly, inflammatory infiltrate was only found when the OPN-vector was combined with a peripheral treatment with pertussis toxin (Ptx), which activated peripheral cells to express the OPN receptor CD44v6. Relative to ?-gal, OPN increased the levels of inflammatory markers, including IL13R?1, CXCR3, and CD40L. In Ptx-treated OPN KOs, apoptotic TUNEL+ cells surrounding the OPN expression site increased, compared to ?-gal. Together, these results show that local OPN expression combined with a peripheral inflammatory stimulus, such as Ptx, may be implicated in the development of brain inflammation and induction of cell death, by driving a molecular pattern characteristic of cytotoxicity. These are characteristics of inflammatory pathologies of the CNS in which OPN upregulation is a hallmark.
  • Upregulation of osteopontin (OPN) is a characteristic of central nervous system pathologies. However, the role of OPN in inflammation is still controversial, since it can both prevent cell death and induce the migration of potentially damaging inflammatory cells. To understand the role of OPN in inflammation and cell survival, we expressed OPN, utilizing an adenoviral vector, in the caudoputamen of mice deficient in OPN, using beta-galactosidase- (β-gal-) expressing vector as control. The tissue pathology and the expression of proinflammatory genes were compared in both treatments. Interestingly, inflammatory infiltrate was only found when the OPN-vector was combined with a peripheral treatment with pertussis toxin (Ptx), which activated peripheral cells to express the OPN receptor CD44v6. Relative to β-gal, OPN increased the levels of inflammatory markers, including IL13Rα1, CXCR3, and CD40L. In Ptx-treated OPN KOs, apoptotic TUNEL+ cells surrounding the OPN expression site increased, compared to β-gal. Together, these results show that local OPN expression combined with a peripheral inflammatory stimulus, such as Ptx, may be implicated in the development of brain inflammation and induction of cell death, by driving a molecular pattern characteristic of cytotoxicity. These are characteristics of inflammatory pathologies of the CNS in which OPN upregulation is a hallmark.

subject areas

  • Animals
  • Antigens, CD44
  • Brain
  • Cell Death
  • Gene Expression Profiling
  • Gene Expression Regulation
  • In Situ Nick-End Labeling
  • Inflammation
  • Macrophages
  • Mice
  • Mice, Knockout
  • Osteopontin
  • Pertussis Toxin
  • Phenotype
  • T-Lymphocytes
  • beta-Galactosidase
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Identity

PubMed Central ID

  • PMC4265371

International Standard Serial Number (ISSN)

  • 0962-9351

Digital Object Identifier (DOI)

  • 10.1155/2014/358218

PubMed ID

  • 25525298
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Additional Document Info

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  • 358218

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