Cutting Edge: IL-13Rα1 Expression in Dopaminergic Neurons Contributes to Their Oxidative Stress–Mediated Loss following Chronic Peripheral Treatment with Lipopolysaccharide
| Autor: | Daniel K. Nomura, Bruno Conti, Indrek Saar, Kwang-Soo Kim, Manuel Sanchez-Alavez, Maria Cecilia Garibaldi Marcondes, Brad E. Morrison, Tamas Bartfai, Pamela Maher, Shuei Sugama, Alejandro Sanchez-Gonzalez |
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| Rok vydání: | 2012 |
| Předmět: |
Lipopolysaccharides
Immunology Inflammation Substantia nigra Biology medicine.disease_cause Article Pathogenesis Mice medicine Animals Humans Immunology and Allergy Genetic Predisposition to Disease Mice Knockout chemistry.chemical_classification Reactive oxygen species Cell Death Pars compacta Dopaminergic Neurons Neurodegeneration Dopaminergic Genetic Diseases X-Linked Parkinson Disease medicine.disease Interleukin-13 Receptor alpha1 Subunit Cell biology Mice Inbred C57BL Disease Models Animal Oxidative Stress chemistry Chronic Disease medicine.symptom Oxidative stress |
| Zdroj: | The Journal of Immunology. 189:5498-5502 |
| ISSN: | 1550-6606 0022-1767 |
| Popis: | Inflammation and its mediators, including cytokines and reactive oxigen species, are believed to contribute to neurodegeneration. In the mouse brain, we found that the interleukin 13 receptor alpha 1 chain (IL-13Rα1) was expressed in the dopaminergic (DA) neurons of the substantia nigra pars compacta which are preferentially lost in human Parkinson’s disease (PD). Mice deficient for Il13ra1 exhibited resistance to loss of DA neurons in a model of chronic peripheral inflammation using bacterial lipopolysaccharide. Interleukin-13, as well as interleukin-4, potentiated the cytotoxic effects of t-butyl hydroperoxide and hydrogen peroxide on mouse dopaminergic MN9D cells. Collectively, our data indicate that expression of IL-13Rα1 on DA neurons can increase their susceptibility to oxidative stress-mediated damage thereby contributing to their preferential loss. In humans, Il13ra1 lies on the X chromosome within the PARK12 locus of susceptibility to PD suggesting that IL-13Rα1 may have a role in the pathogenesis of this neurodegenerative disease. |
| Databáze: | OpenAIRE |
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