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

• Published in: Scientific reports Vol. 10; no. 1; p. 20259
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 20.11.2020; Nature Publishing Group
• Subjects: 631/378; 631/45; Alzheimer's disease; Animals; Antibodies; Carrier Proteins - genetics; Cell Communication - physiology; Central nervous system; Communication; Cytokines; Cytokines - genetics; Humanities and Social Sciences; Inflammation; Inflammation - metabolism; Kinases; Laboratory animals; Lipopolysaccharides; Male; Mice; Mice, Inbred C57BL; Mice, Transgenic; Microglia; Microglia - cytology; mRNA; multidisciplinary; Nervous system; Neuromodulation; Neurons - cytology; NF-κB protein; Nitrites; Phenotypes; Phosphatase; Phosphorylation; Pleiotrophin; Potentiation; Prefrontal cortex; Protein-tyrosine-phosphatase; Proteins; Receptor-Like Protein Tyrosine Phosphatases, Class 5 - physiology; Science; Science (multidisciplinary); Transgenic mice
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-020-76415-5

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.