Cutting edge: IL-13Rα1 expression in dopaminergic neurons contributes to their oxidative stress-mediated loss following chronic peripheral treatment with lipopolysaccharide

• Published in: The Journal of immunology (1950) 2012-12, Vol.189 (12), p.5498-5502
• Main Authors: Morrison, Brad E, Marcondes, Maria Cecilia Garibaldi, Nomura, Daniel K, Sanchez-Alavez, Manuel, Sanchez-Gonzalez, Alejandro, Saar, Indrek, Kim, Kwang-Soo, Bartfai, Tamas, Maher, Pamela, Sugama, Shuei, Conti, Bruno
• Format: Article
• Language: English
• Subjects: Animals; Cell Death - genetics; Cell Death - immunology; Chronic Disease; Disease Models, Animal; Dopaminergic Neurons - immunology; Dopaminergic Neurons - metabolism; Dopaminergic Neurons - pathology; Genetic Diseases, X-Linked - genetics; Genetic Predisposition to Disease - etiology; Humans; Inflammation - genetics; Inflammation - immunology; Inflammation - pathology; Interleukin-13 Receptor alpha1 Subunit - biosynthesis; Interleukin-13 Receptor alpha1 Subunit - deficiency; Interleukin-13 Receptor alpha1 Subunit - genetics; Lipopolysaccharides - administration & dosage; Lipopolysaccharides - toxicity; Mice; Mice, Inbred C57BL; Mice, Knockout; Oxidative Stress - genetics; Oxidative Stress - immunology; Parkinson Disease - genetics; Parkinson Disease - metabolism; Parkinson Disease - pathology
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.1102150

Inflammation and its mediators, including cytokines and reactive oxygen species, are thought to contribute to neurodegeneration. In the mouse brain, we found that IL-13Rα1 was expressed in the dopaminergic (DA) neurons of the substantia nigra pars compacta, which are preferentially lost in human Parkinson's disease. Mice deficient for Il13ra1 exhibited resistance to loss of DA neurons in a model of chronic peripheral inflammation using bacterial LPS. IL-13, as well as IL-4, potentiated the cytotoxic effects of t-butyl hydroperoxide and hydrogen peroxide on mouse DA 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 Parkinson's disease, suggesting that IL-13Rα1 may have a role in the pathogenesis of this neurodegenerative disease.