Osteopontin promotes microglia activation and aggravates neuromyelitis optica via interferon-gamma/nuclear factor kappa B/interleukin-12 signaling

Background Neuromyelitis optica (NMO) is an inflammatory demyelinating disorder featured with the presence of serum aquaporin-4 immunoglobulin G antibodies (AQP4-IgG). Objective Osteopontin (OPN) was reported to be upregulated in NMO; however, the detailed function of OPN in NMO is obscure. Results Downregulation of OPN alleviated demyelination, axonal loss, microglia activation, neutrophil infiltration, inflammatory response and astrocyte apoptosis, but increased neurotrophic factor levels in murine spinal cords. Moreover, knockdown of OPN suppressed the expression of its downstream molecules, including interferon-gamma (IFN-gamma), nuclear factor kappa B (NF-kB) and interleukin-12 (IL-12). Conclusion OPN promotes microglia activation and facilitates the pathogenesis of NMO by activating the IFN-gamma/NF-kB/IL-12 signaling pathway.

Automated summary

Neuromyelitis optica (NMO) is an inflammatory demyelinating disorder associated with upregulated osteopontin (OPN). This study found that downregulation of OPN alleviated demyelination and other pathological features, while increasing neurotrophic factors levels. Furthermore, OPN was shown to activate the IFN-γ/NF-kB/IL-12 signaling pathway, promoting microglia activation and contributing to the pathogenesis of NMO.