| First Author | Fernández-Calle R | Year | 2020 |
| Journal | Sci Rep | Volume | 10 |
| Issue | 1 | Pages | 20259 |
| PubMed ID | 33219280 | Mgi Jnum | J:300228 |
| Mgi Id | MGI:6491085 | Doi | 10.1038/s41598-020-76415-5 |
| Citation | Fernandez-Calle R, et al. (2020) Role of RPTPbeta/zeta in neuroinflammation and microglia-neuron communication. Sci Rep 10(1):20259 |
| abstractText | 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 Tnfalpha mRNA and Ptn mRNA levels in the prefrontal cortex (PFC) of LPS-treated mice. PTN is an inhibitor of Receptor Protein Tyrosine Phosphatase (RPTP) beta/zeta, which is mainly expressed in the central nervous system. We aimed to test if RPTPbeta/zeta is involved in the modulation of neuroinflammatory responses using specific inhibitors of RPTPbeta/zeta (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-kappaB p65 expression, suggesting that RPTPbeta/zeta may be involved in a novel mechanism of potentiation of microglial activation independent of the NF-kappaB 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. RPTPbeta/zeta inhibition in microglial cells disrupted this neurotrophic effect of microglia, suggesting that RPTPbeta/zeta plays a role in the neurotrophic phenotype of microglia and in microglia-neuron communication. |
