Objective: To investigate the effect and related mechanism of retinoid X receptor (RXR) activation on oxidized low-density lipoprotein (ox-LDL) induced differentiation of macrophage into dendritic cell.
Methods: RAW264.7 murine macrophage cell line was cultured with ox-LDL for 48 h in the absence and presence of RXR activator 9-cisRA or SR11237. Cell morphology was observed by phase contrast microscope and cell surface markers involved in dendritic cell immune maturation and activation was analyzed by FACS. Cellular reactive oxygen species production was detected by CM-H2DCFDA fluorescent probe.
Results: ox-LDL-treated RAW264.7 murine macrophage cell line differentiated into dendritic like cells after 48 h and cell surface markers CD40, CD86, CD83, MHC Class II and CD1d were upregulated. These changes could be attenuated by cotreatment with 9-cisRA or SR11237. Upregulated cell surface markers CD40, CD86, CD83, MHC Class II and CD1d by ox-LDL were decreased about 47%, 43%, 48%, 32% and 17% respectively by 9-cisRA and 38%, 38%, 46%, 36% and 32% respectively by SR11237. The effect of 9-cisRA and SR11237 was dose dependent. Cellular reactive oxygen species were significantly increased in ox-LDL-treated RAW264.7 cells (MFI 38.24 +/- 4.20 vs. 4.46 +/- 0.39, P < 0.05) and which was significantly reduced by 9-cisRA (10(-7) mol/L) and SR11237 (10(-6) mol/L) to 12.60 +/- 1.52 and 17.89 +/- 1.91 respectively (all P < 0.05).
Conclusion: RXR activation partly inhibits the differentiation of ox-LDL induced macrophage into dendritic cell by reducing oxidative stress injury.