The Effects of n-3 Polyunsaturated Fatty Acid on Disease Severity and Mesangial Cell in Autoimmune NZB/W F1 Mice

• Main Authors: Lai Ying Ho, 賴瑩荷
• Other Authors: 吳文勉
• Format: Others
• Language: zh-TW
• Published: 2003
• Online Access: http://ndltd.ncl.edu.tw/handle/38540547260797138796

碩士 === 輔仁大學 === 食品營養學系 === 91 === As the increase of people who dine out and the changing of their dietary habits, the intake of dietary fat has increased significantly. However, increased intake of fat will lead to higher occurrence of obesity, cardiovascular diseases, cancer and autoimmune disease. Studies have shown that the intake of n-3 polyunsaturated fatty acid will affect human immune response and prevent diseases. Systemic lupus erythematosus (SLE) is one kind of autoimmune disease, many kinds of autoantibodies can be detected in the patient’s serum when affected. These autoantibodies will combined with complement proteins which then formed the immune complex, which many deposit in the kidney and develop further glomerulonephritis. In this study we fed female NZB/NZW F1 mice with 20% (w/w) fish oil/ safflower oil or lard/ soybean oil-based diets for twelve weeks. NZB/NZW F1 female mice of fish oil-fed group could mitigate the symptom of proteinuria, lower anti-dsDNA IgG antibody in sera and the percentage of cell surface major histocompatibility complex class II of splenocyte also decreases significantly compare to lard/ soybean oil-fed group. As glomerulonephritis is a common clinical symptom of SLE, some investigator demonstrated that the abnormal proliferative phenomenon of kidney mesangial cell were is closely related to glomerulonephritis. In this study we set up the primary mesangial cell-culture system of both female NZB/NZW F1 and DBA-2/NZW F1 mice. This will facilate our investigation on mechanisms of SLE. We compare the difference of the mesangial cell from two isogenic strains of mice. DBA-2/NZW F1 (H-2d/u) mice is a non-autoimmune strain bearing MHC class II molecules indentical to those in NZB/NZW F1 (H-2d/u) mice. The purity of mesangial cell was confirmed by using immunohistochemistry staining. Effect of treatments with various concentration of EPA or DHA on mesangial cell purified from two strains of mice will compared in this study. As the concentration of EPA more than 300 μM, the proliferative effect of these two kinds of mesangial cell were significantly lower than cell alone (control) (p<0.05). The supernatant of monocyte chemoattractant protein-1 (MCP-1) in cell was decreased as the concentration of EPA increase. The inhibitive trend of DHA on proliferative of mesangial cell were alike as EPA when its concentration reach to 100 μM. Moreover, the phagocytic activity of the NZB/NZW F1 derived mesangial cell co-culture with 300 μM of DHA was significantly lower than control cell. There were no difference among the secretion of TGF-β1、TNF-α、IL-6 or nitrite oxide in supernatants of mesangial cell cocultured with various concentration of n-3 PUFA. Although n-3 PUFA had the same effect in the secretion of MCP-1 between two strains of mesangial cell, the cell from the female NZB/NZW F1 mice tends to enhance potentical of MCP-1 secretion. In summarize, as the concentration of EPA or DHA increased, the proliferation and secretion of MCP-1 by mesangial cell were decreased when compare to control group. Therefore the mechanisms of fish oil on the immunoregulation of SLE, may through the decreased phagocytic activity which will involved the autoantigen presentation. By the way, n-3 PUFA can inhibit the secretion of MCP-1 of mesangial cell, therefore it has beneficial effects on alleviation of the chronic glomerulonephritis. Further understanding the modulator roles of n-3 PUFA between these two strains of mesangial cell were important and highlight the potential therapeutic application in inflammation related glomerulonephritis.