Effects Of Fc?RIIB Overexpression On Oligomeric A?-exposed Microglia

Background:Microglia is best known as immune cel s of CNS and plays a crucial role in removing excessive A?. The well balanced physiological functions of A? account for neurotransmitter and neurotrophy of synapse by virtue of surveillance and scavenger of microglia. A? has been proved to be the pathogenic factor of Alzheimer's disease. During the progression of AD, microglia is disease modified under the burden of A? Plaque. From the initial effective activation to the later paralysis, Mass of A? has successfully transformed microglia to the immunosuppressed state. The devastating capacity to spark inflam matory response and inability to phagocytize A? has created a vicious cycle between microglia dysfunction and A? impairment. Fc?RIIB is the only inhibitory receptor bearing the specific motif of tyrosine-based inhibition motif(ITIM) within its cytoplasmic region and can recruit SHP-1 or- 2 upon contradicting other activating Fc?Rs functions of endocytosis and cytokine release. Fc?RIIB may induce apoptosis of B cells independent of ITIM motif. It's reported Fc?RIIB is significantly upregulated in the hippocampus of AD brains and neuronal cels exposed to synthetic A?, thus mediating A? neurotoxicity and neurodegeneration; over expression of Fc?RIIB in the macrophage is sufficient to decrease glial phagocytosis and chemotaxis. As Fc?RIIB is rich expressed in the microglia, largely is unknown about the link between the microglia dysfuction and Fc?RIIB. Here, we construct h- Fc?RIIB to infect microglia under the low dosage of A? to simulate the same mechanism but different phenotype of microglia.Objective: To determine whether Fc?RIIB mediating neuronal toxicity reflected in the same way of microglia.Methods: Using different species of A? in a time and dosage scale to decide the optimal condition by western blotting and CCK8; confirming the result by immunostaining of Fc?RIIB in BV-2 and primary microglia; over expression of Fc?RIIB, cell extracts were subjected to western blotting by applying apotosis markers of caspase 3, caspase 12, PARP and A? downstream effector molecules of JNK or ERK; over expression of Fc?RIIB, DNA strand break was measured by Tunel and microglia activation was measured by the intensity of colocalization of CD68 and GFP(h-Fc?RIIB).Result: Fc?RIIB was upregulated by oligomeric A? at the time peak of 12 h after incubation; Fc?RIIB expression was increased in the BV-2 and primary microglia by Fc?RIIB immunofluorence; apoptosis markers associated with p-JNK/JNK selectively augmented by over expression of Fc?RIIB under low dosage of A?; over expression of Fc?RIIB activated microglia.Conclusion: Fc?RIIB mediated A? incuced microglia activation and the caspase 12/caspase 3 associated apoptosis, the mechanisms involved JNK upregulation and ER stress.