ABSTRACT
Our study aimed to investigate the effects of interleukin-4 (IL-4) on macrophage polarization, as well as its role in the development of atherosclerosis. Human peripheral blood mononuclear cells (PBMCs) were isolated and randomly divided into 3 groups: control group, ox-LDL group, and ox-LDL + IL-4 groups. The expression of M1/M2 macrophage surface markers such as TNF-α, CD68, and CD206 were analyzed by western blot. Cell viability was determined using the MTT assay. Measurement of CD86/CD206 expression ratio (M1/M2 ratio) was performed via flow cytometry. In addition, ApoE(-/-) mice on a C57BL/6 background were subjected to high-fat diets, and were used as a model of atherosclerosis. Atherosclerotic lesion area was quantified after mice were treated with ox-LDL and IL-4. Finally, expression of phosphorylated MAPK signaling molecules such as p-ERK and p-JNK was quantified using western blot. The expression of TNF-α and CD86 markedly increased after cells were treated with ox-LDL, whereas the expression of CD206 markedly increased after PBMCs were treated with IL-4. It is possible that IL-4 could decrease ox-LDL-induced cell viability and the CD86/CD206 (M1/M2) ratio. Additionally, IL-4 intervention attenuated ox-LDL-induced atherosclerotic lesions in ApoE(-/-) mice, and decreased ox- LDL-induced expression of p-ERK and p-JNK. Our findings indicate that IL-4 may induce macrophages to take on an M2 phenotype in order to resolve inflammation via inhibition of MAPK signaling pathways, thereby protecting against atherosclerosis. IL-4 may serve as an intervention target for atherosclerosis.
Subject(s)
Atherosclerosis/drug therapy , Atherosclerosis/metabolism , Interleukin-4/pharmacology , Interleukin-4/therapeutic use , Macrophages/drug effects , Macrophages/metabolism , Animals , Apolipoproteins E/metabolism , Cells, Cultured , Lipoproteins, LDL/metabolism , Mice , Mice, Inbred C57BL , Phosphorylation/drug effects , Signal Transduction/drug effectsABSTRACT
We investigated the killing effect of low-intensity ultrasound combined with 5-aminolevulinic acid (5-ALA) on the rat osteosarcoma cell line UMR-106. Logarithmic-phase UMR-106 cells were divided into a control group, ultrasound group and 5-ALA group. The cell apoptotic rate, production of reactive oxygen species, and the change in mitochondrial membrane potential were analyzed by flow cytometry; ultrastructural changes were observed by transmission electron microscopy. Using low-intensity ultrasound at 1.0 MHz and 2.0 W/cm(2) plus 5-ALA at a concentration of 2 mM, the apoptotic rate of the sonodynamic therapy group was 27.2 ± 3.4% which was significantly higher than that of the control group, ultrasound group, and 5-ALA group (P < 0.05). The production of reactive oxygen species was 32.6 ± 2.2% and the decrease in mitochondrial membrane potential was 39.5 ± 2.5%. The 33342 staining showed nuclear condensation and fragmentation in the ultrasound group and 5-ALA group. Structural changes in the cell membrane, mitochondria, Golgi apparatus, and other organelles observed by transmission electron microscopy included formation of apoptotic bodies. The killing effect of low-intensity ultrasound combined with 5-ALA on UMR-106 cells was significant. Cell apoptosis played a vital role in the killing effect, and the mitochondria pathway contributed to the apoptosis of UMR-106 cells.
Subject(s)
Aminolevulinic Acid/pharmacology , Apoptosis/drug effects , Apoptosis/radiation effects , Ultrasonic Waves/adverse effects , Cell Line, Tumor , Flow Cytometry , Humans , Osteosarcoma/metabolism , Osteosarcoma/therapy , Reactive Oxygen Species/metabolism , Ultrasonic TherapyABSTRACT
The aim of this study was to explore postoperative changes in prostate-specific antigen (PSA) levels and risk factors that influence the clinical effects of ultrasound-guided permanent [(125)I] seed implantation in the treatment of prostate cancer. From July 2009 to December 2012, 41 prostate cancer patients who underwent transrectal ultrasound-guided [(125)I] seed implantation were followed up for 3-56 months. The patients were divided into 2 groups according to their results: group A, benign rebound group, 31 cases; and group B, biochemical relapse group, 10 cases. A blood analysis of group A showed that the initial PSA rise after a nadir occurred postoperatively at 16.8 ± 1.2 months, and in 65.8% (27/41) patients the rise occurred during 15-27 weeks. For group B, the initial PSA rise after a nadir occurred postoperatively at 30.2 ± 2.1 months, and the difference in the time parameter of the initial PSA rise after the nadir was statistically significant between the 2 groups (P < 0.01). During treatment, age was shown to be a risk factor for group A (P = 0.0027, P < 0.01). Postoperative changes in PSA levels after ultrasound-guided permanent [(125)I] seed implantation contributed to the assessment of the clinical treatment effects.