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

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 Tnf alpha 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 RPTP beta/zeta is involved in the modulation of neuroinflammatory responses using specific inhibitors of RPTP beta/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-kappa B p65 expression, suggesting that RPTP beta/zeta may be involved in a novel mechanism of potentiation of microglial activation independent of the NF-kappa B 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. RPTP beta/zeta inhibition in microglial cells disrupted this neurotrophic effect of microglia, suggesting that RPTP beta/zeta plays a role in the neurotrophic phenotype of microglia and in microglia-neuron communication.