The Effect of Fetuin-A on the Polarization of Macrophages in a Mouse Cell Line

During the multiple sclerosis (MS) disease course, Fetuin-A is upregulated in the spinal cord fluid.  Expression of Fetuin-A effects macrophage differentiation and migration into the nervous system.  Macrophages in the central nervous system (CNS), called microglial cells, get polarized and become one of two types, M1 or M2.  The M1 type is proinflammatory and causes inflammation at the lesion site in the CNS and the M2 type is anti-inflammatory and fights the inflamed response.  Previous studies have shown that blocking macrophage trafficking reduces the extent of Experimental Autoimmune Encephalomyelitis (EAE), a mouse model for MS.  We wanted to test the effect of Fetuin on the polarization and activation of microglial cells.  We used undifferentiated mice microglial cells (BV-2 cell line) and polarized the cells to be either M1 or M2 in the presence and absence of Fetuin.  We polarized cells by adding various cytokines GM-CSF, IFN-gamma, M-CSF, IL-4, and IL-13 and performed RNA extraction and quantitative polymerase chain reaction (qPCR) to assess protein expression.  We compared the data to known markers to see if we successfully polarized the cells and if the two types of cells were upregulated or downregulated in the presence or absence of Fetuin-A. We used NOS as the M1 marker and Arg1 as the M2 marker.  Our results show an increase in the number of cells polarized to the M1 type in the presence of Fetuin-A and a decrease in the number of cells polarized to the M2 type in the absence of Fetuin-A.  These data suggests that Fetuin-A plays a role in the inflammation of the CNS by the means of macrophage polarization.