Osteopontin Expression in the Brain Triggers Localized Inflammation and Cell Death When Immune Cells Are Activated by Pertussis Toxin
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...
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| Format: | Article |
| Language: | English |
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Wiley
2014-01-01
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| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2014/358218 |
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| author | Maria Cecilia Garibaldi Marcondes Ryan Ojakian Nikki Bortell Claudia Flynn Bruno Conti Howard S. Fox |
| author_facet | Maria Cecilia Garibaldi Marcondes Ryan Ojakian Nikki Bortell Claudia Flynn Bruno Conti Howard S. Fox |
| author_sort | Maria Cecilia Garibaldi Marcondes |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-f4b21032b52041c88b75b43bddf2137e |
| institution | Kabale University |
| issn | 0962-9351 1466-1861 |
| language | English |
| publishDate | 2014-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj-art-f4b21032b52041c88b75b43bddf2137e2025-02-03T06:01:23ZengWileyMediators of Inflammation0962-93511466-18612014-01-01201410.1155/2014/358218358218Osteopontin Expression in the Brain Triggers Localized Inflammation and Cell Death When Immune Cells Are Activated by Pertussis ToxinMaria Cecilia Garibaldi Marcondes0Ryan Ojakian1Nikki Bortell2Claudia Flynn3Bruno Conti4Howard S. Fox5Molecular and Cellular Neuroscience Department, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USAMolecular and Cellular Neuroscience Department, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USAMolecular and Cellular Neuroscience Department, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USAImmunology and Microbial Science Department, The Scripps Research Institute, La Jolla, CA 92037, USAMolecular and Cellular Neuroscience Department, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USADepartment of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE 68198, USAUpregulation 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.http://dx.doi.org/10.1155/2014/358218 |
| spellingShingle | Maria Cecilia Garibaldi Marcondes Ryan Ojakian Nikki Bortell Claudia Flynn Bruno Conti Howard S. Fox Osteopontin Expression in the Brain Triggers Localized Inflammation and Cell Death When Immune Cells Are Activated by Pertussis Toxin Mediators of Inflammation |
| title | Osteopontin Expression in the Brain Triggers Localized Inflammation and Cell Death When Immune Cells Are Activated by Pertussis Toxin |
| title_full | Osteopontin Expression in the Brain Triggers Localized Inflammation and Cell Death When Immune Cells Are Activated by Pertussis Toxin |
| title_fullStr | Osteopontin Expression in the Brain Triggers Localized Inflammation and Cell Death When Immune Cells Are Activated by Pertussis Toxin |
| title_full_unstemmed | Osteopontin Expression in the Brain Triggers Localized Inflammation and Cell Death When Immune Cells Are Activated by Pertussis Toxin |
| title_short | Osteopontin Expression in the Brain Triggers Localized Inflammation and Cell Death When Immune Cells Are Activated by Pertussis Toxin |
| title_sort | osteopontin expression in the brain triggers localized inflammation and cell death when immune cells are activated by pertussis toxin |
| url | http://dx.doi.org/10.1155/2014/358218 |
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