ABSTRACT
OBJECTIVE: To investigate the preventive effect of rock salt aerosol on the development of silicosis in rats. METHODS: The specific pathogen free adult male SD rats were randomly divided into normal control group, rock salt control group, silicosis model group and rock salt intervention group, 18 rats in each group. Rats in the silicosis model group and the salt rock intervention group were treated with silica dust at the concentration of 2 000.0 mg/m~3 by dynamic dusting method for 3 hours daily. Rats in the rock salt control group and the rock salt intervention group inhaled the rock salt aerosols with the mass concentration of 20.0 mg/m~3 for 30 minutes daily. The normal control group was not treated with the dust or rock salt aerosol. At the time points of 14, 28 and 56 days after exposure to dust or rock salt aerosol, 6 rats were randomly selected from each group and samples were collected. The pathological change of lung was observed, the total cell count in the bronchoalveolar lavage fluid(BALF) was performed, the enzyme-linked immunosorbent assay was used to detect the change of transforming growth factor-β(TGF-β) in BALF, surfactant D(SP-D) and superoxide dismutase(SOD) in lung tissue. RESULTS: The results of hematoxylin-eosin and Masson staining showed that the inflammatory changes of lung tissue and the pulmonary interstitial fibrosis in the rock salt intervention group were less severer than that in the silicosis model group. At 14, 28, and 56 days after dust exposure, the total cell counts in BALF and SP-D levels in lung tissue of rats in silicosis model group and rock salt intervention group were higher(P<0.05), the SOD activities in lung tissue were lower(P<0.05), as well as the TGF-β levels in BALF in silicosis model group were higher(P<0.05),compared with the normal control group and rock salt control group. The total cell counts and TGF-β levels in BALF, and SP-D levels in lung tissue of rock salt intervention group were lower(P<0.05), the SOD activities in lung tissue were higher(P<0.05), compared with the silicosis model group. CONCLUSION: Rock salt aerosol intervention may delay the pathogenesis of silicosis by improving the inflammatory response, regulating oxidative stress and reducing interstitial fibrosis of lungs.
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.
ABSTRACT
OBJECTIVE: To investigate the role of cyclophilin A in the foaming process of macrophages induced by free silica( SiO_2). METHODS: The human peripheral blood mononuclear cell THP-1 in the logarithmic growth phase was induced and differentiated into human macrophages with phorbol 12-myristate 13-acetate at 100 μg/L for 48 hours. The cells were divided into 4 groups. The cells in the blank control group were not treated. The cells in the oxidized low-density lipoprotein( ox-LDL) control group were treated with a final concentration of 50 mg/L ox-LDL. The cells of 50 mg/L SiO_2 group were treated with 50 mg/L of SiO_2 and ox-LDL. The cells of 100 mg/L SiO_2 group were treated with 100 mg/L of SiO_2 and 50 mg/L of ox-LDL. After treatment of cells for 48 h,cell viability was measured by MTS method. The lipid accumulation of cells was observed by oil red O staining and colorimetric method; the expression of cyclophilin A in cell supernatant was detected by enzyme-linked immunosorbent assay,and the expression of cyclophilin A in the cells was detected by Western blotting. RESULTS: The cell viability was the highest when the concentration of SiO_2 was 100 mg/L compared with the control and other four SiO_2groups( P < 0. 01). The cell foaming change in the 100 mg/L SiO_2 group observed by oil red O staining significantly increased compared with the blank control group. The expression of total cholesterol,free cholesterol increased in the ox-LDL control group,50 mg/L SiO_2 group and 100 mg/L SiO_2group( P <0. 05),and the cholesterol specific gravity increased( P < 0. 05) compared with the blank control group,meanwhile the expression of cyclophilin A in the cell supernatant increased( P < 0. 05),and the expression in the macrophages cells decreased( P < 0. 05). CONCLUSION: Cyclophilin A is involved in the foaming process of macrophages induced by SiO_2.