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Autor: Raúl, Lagos-Cabré, Alvaro, Alvarez, Milene, Kong, Francesca, Burgos-Bravo, Areli, Cárdenas, Edgardo, Rojas-Mancilla, Ramón, Pérez-Nuñez, Rodrigo, Herrera-Molina, Fabiola, Rojas, Pascal, Schneider, Mario, Herrera-Marschitz, Andrew F G, Quest, Brigitte, van Zundert, Lisette, Leyton
Rok vydání: 2017
Předmět:
Zdroj: Journal of Neuroinflammation
ISSN: 1742-2094
Popis: Background Neuroinflammation involves cytokine release, astrocyte reactivity and migration. Neuronal Thy-1 promotes DITNC1 astrocyte migration by engaging αVβ3 Integrin and Syndecan-4. Primary astrocytes express low levels of these receptors and are unresponsive to Thy-1; thus, inflammation and astrocyte reactivity might be necessary for Thy-1-induced responses. Methods Wild-type rat astrocytes (TNF-activated) or from human SOD1G93A transgenic mice (a neurodegenerative disease model) were used to evaluate cell migration, Thy-1 receptor levels, signaling molecules, and reactivity markers. Results Thy-1 induced astrocyte migration only after TNF priming. Increased expression of αVβ3 Integrin, Syndecan-4, P2X7R, Pannexin-1, Connexin-43, GFAP, and iNOS were observed in TNF-treated astrocytes. Silencing of β3 Integrin prior to TNF treatment prevented Thy-1-induced migration, while β3 Integrin over-expression was sufficient to induce astrocyte reactivity and allow Thy-1-induced migration. Finally, hSOD1G93A astrocytes behave as TNF-treated astrocytes since they were reactive and responsive to Thy-1. Conclusions Therefore, inflammation induces expression of αVβ3 Integrin and other proteins, astrocyte reactivity, and Thy-1 responsiveness. Importantly, ectopic control of β3 Integrin levels modulates these responses regardless of inflammation. Electronic supplementary material The online version of this article (10.1186/s12974-017-0968-5) contains supplementary material, which is available to authorized users.
Databáze: OpenAIRE
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