Role of RPTPβ/ζ in neuroinflammation and microglia-neuron communication.

Autor: Fernández-Calle, Rosalía, Galán-Llario, Milagros, Gramage, Esther, Zapatería, Begoña, Vicente-Rodríguez, Marta, Zapico, José M., de Pascual-Teresa, Beatriz, Ramos, Ana, Ramos-Álvarez, M. Pilar, Uribarri, María, Ferrer-Alcón, Marcel, Herradón, Gonzalo
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Zdroj: Scientific Reports; 11/20/2020, Vol. 10 Issue 1, p1-12, 12p
Abstrakt: Pleiotrophin (PTN) is a cytokine that is upregulated in different neuroinflammatory disorders. Using mice with transgenic PTN overexpression in the brain (Ptn-Tg), we have found a positive correlation between iNos and Tnfα mRNA and Ptn mRNA levels in the prefrontal cortex (PFC) of LPS-treated mice. PTN is an inhibitor of Receptor Protein Tyrosine Phosphatase (RPTP) β/ζ, which is mainly expressed in the central nervous system. We aimed to test if RPTPβ/ζ is involved in the modulation of neuroinflammatory responses using specific inhibitors of RPTPβ/ζ (MY10 and MY33-3). Treatment with MY10 potentiated LPS-induced microglial responses in the mouse PFC. Surprisingly, MY10 caused a decrease in LPS-induced NF-κB p65 expression, suggesting that RPTPβ/ζ may be involved in a novel mechanism of potentiation of microglial activation independent of the NF-κB p65 pathway. MY33-3 and MY10 limited LPS-induced nitrites production and iNos increases in BV2 microglial cells. SH-SY5Y neuronal cells were treated with the conditioned media from MY10/LPS-treated BV2 cells. Conditioned media from non-stimulated and from LPS-stimulated BV2 cells increased the viability of SH-SY5Y cultures. RPTPβ/ζ inhibition in microglial cells disrupted this neurotrophic effect of microglia, suggesting that RPTPβ/ζ plays a role in the neurotrophic phenotype of microglia and in microglia-neuron communication. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index
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