Effect of LXR-ABCA1 signaling pathway on free silica-induced macrophage foaming / 中国职业医学

ABSTRACT

OBJECTIVE: To investigate the effect of liver X receptor(LXR)-adenosine triphosphate-binding cassette transporter A1(ABCA1) signaling pathway on the free silica(SiO_2)-induced foaming of macrophages. METHODS: Human histiocytic lymphoma U937 cells were induced to differentiate into macrophages by phorbol myristate acetate. The macrophages at logarithmic growth phase were randomly divided into 4 groups the cells in the control group received no treatment, the cells in the SiO_2 stimulation group were stimulated with SiO_2 suspension at a dose of 50 mg/L, and the cells in the oxidized low-density lipoprotein(ox-LDL) group were treated with ox-LDL at the dosed 50 mg/L, the cells in the combination group were simultaneously stimulated with SiO_2 suspension and ox-LDL at a dose of 50 mg/L. Cells were collected after 48 hours of culture. Macrophage foaming was observed by oil red O staining. The levels of total cholesterol(TC), free cholesterol(FC), cholesteryl ester(CE) and CE specific gravity(CE%) in macrophages were detected using a microplate reader. The expression of LXR and ABCA1 was detected using Western blotting. RESULTS: The results of the oil red O staining showed that all the macrophages in the SiO_2 stimulation group, ox-LDL group and the combination group had foaming changes. The degree of foaming in the macrophages in the combination group was higher than that in the other two groups. The levels of TC, FC, CE and CE% in macrophages increased(P<0.05), and the protein relative expression of LXR and ABCA1 decreased(P<0.05), in SiO_2 stimulation group, ox-LDL group and combination group compared with the control group. The macrophages in the combination group were transformed into foam cells. The levels of TC, FC, CE and CE% in macrophages of the combination group increased(P<0.05), and the protein relative expression of LXR and ABCA1 decreased(P<0.05), compared with the SiO_2 stimulation group and the ox-LDL group. CONCLUSION:sFree SiO_2 can induce foaming of macrophages, and ox-LDL in combination with SiO_2 has a synergistic effect on the formation of foaming of macrophages.The process of macrophage foaming may be achieved by inhibiting the LXR-ABCA1 signaling pathway.