[AIM] Zn²⁺ plays an important role in both M1 and M2 microglia. However, the role of Zn²⁺ on microglial M2/M1 switch is unclear. In this study, we examined whether extracellular Zn²⁺ affects microglial M2/M1 switch, and the involvement of ZIP zinc transporter.
[METHODS] Mouse microglial cell line, BV2 cells, were polarized to M2 phenotype by IL-4 (10 ng/mL) in the presence of ZnCl₂ (30 µM), and then were switched to M1 phenotype by lipopolysaccharide (LPS, 100 ng/mL). The level of IL-6, a marker of M1 phenotype, in the medium was measured by ELISA. The mRNA expressions of ZIP in IL-4 treated cells were examined by qRT-PCR. ZIP8 distribution in IL-4-treated cells was investigated by immunostaining.
[RESULTS] Treatment of IL-4-polarized M2 phenotype of BV2 cells with LPS resulted in a significant elevation of IL-6 levels. However, when BV2 cells were polarized to M2 phenotype by IL-4 in the presence of Zn²⁺ before LPS treatment, level of IL-6 was found to be significantly lower. In addition, BV2 cells treated with IL-4 exhibited increased ZIP8 mRNA expression. The ZIP8 protein was observed on the plasma membrane of BV-2 cells.
[CONCLUSION] In the present study, our findings suggest that extracellular Zn²⁺ suppress microglial M2/M1 switch, which is involved in Zn²⁺ uptake via zinc transporter ZIP8.