Regulation of triggering receptor expressed on myeloid cells-2 (TREM2) expression in microglia
Background: Activation of microglia is a feature of several neurodegenerative diseases. TREM2 is an immune receptor expressed by macrophages and microglia, which negatively regulates immune responses of these cells. Microglia-associated brain inflammation may be alleviated by up-regulation of microglial TREM2. However, it is unclear whether regulation of TREM2 expression in microglia is consistent with classical (M1) and alternative (M2) activation pathways of macrophages. Aims: To determine if microglial expression of TREM2 and its adaptor protein DAP12 is regulated by M1 or M2 activation. Methods: BV2 microglial cells were stimulated by LPS, IL-4, or HMGB1, respectively, with PBS as control. 6-hour and 24-hour stimulations were applied to each treatment. Expression of TREM2, DAP12, iNOS, IL-1β and Arg-1 was analysed by quantitative real-time PCR. Relative quantification of results was performed using delta delta Ct method. One-sample Student’s t-test was used to detect difference between treatment and control. Results: Induced polarisation toward M1 and M2 activation phenotypes were confirmed in microglia. TREM2 was down regulated by LPS (Mean ± SD: 0.95±0.56 for 6h and 0.40±0.07 for 24h) and up regulated by IL-4 (6h: 4.36±2.99; 24h: 1.74±0.68) and HMGB1 (6h: 4.56±4.20; 24h: 1.20±0.20). DAP12 presented no obvious difference between treatments. Conclusion: Microglia are subjected to M1 and M2 polarisation. M2 cytokine IL-4 up regulates both TREM2 and Arg-1, which attenuate brain inflammation. Regulation of microglial TREM2 provides a promising target for treatment of neurodegenerative diseases.