A Critical Role for Immune System-released Activating Agent (Israa) in the Ontogenetic Development of the Brain

Abstract Background: The Immune System-Released Activating Agent (ISRAA) was discovered as a novel molecule that functions as a mediator between the nervous and immune systems in response to a nervous stimulus following an immune challenge. Thisresearch investigated the role ofISRAA)in promoting the ontogeny of the mouse brain. Methods: Astrocyte cultures were prepared from two-month-old BALB/c mice. Recombinant ISRAA protein was used to stimulate astrocyte cultures. Immunohistochemistry and ELISA were utilized to measure ISRAA andIFN-g levels, IFN-gR expression and STAT1 nuclear translocation. MTT-assay was used to evaluate cellular survival and proliferation. To assess astrocyte cell lysates and tyrosine-phosphorylated proteins, SDS-PAGE and western blot were used.Results: ISRAA was highly expressed in mouse embryonic astrocytes,depending on cell age. Astrocytes agedseven days (E7) showed increased proliferation and diminisheddifferentiation, while 21-day-old (E21)astrocytes depictedreversed effects. ISRAAstimulated the tyrosine phosphorylation of numerous cellular proteins and thenuclear translocation of STAT1. IFN-g was vital for ISRAAactionas ISRAA induced IFN-gin both age groups, but only E21 astrocytes expressed IFN-gR. Conclusion: The results suggest that ISRAA is cruciallyinvolved in mouse brain development through the cytokine network involving IFN-g.