TY - JOUR TI - Role of RPTPβ/ζ in neuroinflammation and microglia-neuron communication AU - Fernández-Calle, Rosalía AU - Galán-Llario, Milagros AU - Gramage, Esther AU - Zapatería, Begoña AU - Vicente-Rodríguez, Marta AU - Zapico, José M. AU - de Pascual-Teresa, Beatriz AU - Ramos, Ana AU - Ramos-Álvarez, M. Pilar AU - Uribarri, María AU - Ferrer-Alcón, Marcel AU - Herradón, Gonzalo T2 - Scientific Reports AB - 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. DA - 2020/11/20/ PY - 2020 DO - 10.1038/s41598-020-76415-5 DP - www.nature.com VL - 10 IS - 1 SP - 20259 LA - en SN - 2045-2322 UR - https://www.nature.com/articles/s41598-020-76415-5 Y2 - 2020/11/20/18:58:29 ER -