Effects of retinoid X receptor activation on lightly oxidized low-density lipoprotein induced cell proliferation of macrophages: experiment with murine RAW264.7 cells

Objective To investigate the effects and mechanism of retinoid X receptor (RXR) activation on macrophages proliferation induced by lightly oxidized low-density lipoprotein (LoxLDL).Methods Serum-starved mouse macrophages of the line RAW264. 7 were stimulated with 20 μg/mLLoxLDL for 24 h to induce proliferation in the absence or presence of varying doses of RXR special agonist 9-cis retinoid acid (RA). The cell viability was assayed by MTT method. The DNA synthesis was assayed by BrdU ELISA. The apoptotic percentage of cells was measured by flow cytometry using propidium iodide (PI) staining. Nur77 and RARβ protein expressions were detected by Western blotting. Results After treated by LoxLDL for 24 h, the cell viability and DNA synthesis ( A value) of the RAW264.7 ceils were increased by 0.79±0.12 and 1.81±0.31 respectively. Co-incubated with LoxLDL and 10-s mol/L and 10-7 mol/L 9-cisRA the ceil viability decreased to 0.43±0.10 and 0.26±0.07 respectively( both P＜0. 05 ), and the DNA synthesis decreased to 1.14±0.43 and 0.72±0.06 respectively(both P＜0.05 ) The apoptotic rate of the ceils treated with LoxLDL was (3.08±0.30) %, not significantly different from those of the cells cocultured with LoxLDL and 10-9-10-7 mol/L 9-cisRA (2.74±0.13 ) % , (2.94±0.24) % , and (2.48±0.42) % respectively, all P＞0.05. The orphan nuclear receptor Nur77 protein expression was up-regulated by more than 5 times after LoxLDL treatment. 9-cisRA down-regulates the Nut77 expression and increased the expression of the downstream gene RARβ. Condnsion RXR activation significantly inhibits the macrophage proliferation induced by LoxLDL. The mechanism may be related to the regulation of RXR/Nur77 heterodimer and its downstream gene RARβ. Key words: Coronary arteriosclerosis ;  Lipoprotein, LDL;  Macrophages ;  Retinoid X receptor