Calorie restriction decreases proinflammatory cytokines and polymeric Ig receptor expression in the submandibular glands of autoimmune prone (NZB X NZW)F1 mice
Calorie restriction decreases proinflammatory cytokines and polymeric Ig receptor expression in the submandibular glands of autoimmune prone (NZB X NZW)F1 mice
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DOI：
10.1023/a:1006620130114
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发表时间：
2000-09-01
影响因子：
9.1
通讯作者：
Fernandes, G
中科院分区：
文献类型：
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作者：
Muthukumar, AR;Jolly, CA;Fernandes, G
热量限制或鱼油（富含n-3脂肪酸）补充可改善（NZ B x NZW）F-1（B/W）小鼠的肾小球肾炎和干燥综合征病变。促炎性细胞因子的表达增强和免疫复合物的沉积是干燥综合征发生发展的重要病理事件。在本研究中，我们检查了热量限制和鱼油补充对关键炎症细胞因子[γ干扰素（INF-γ）、白细胞介素-10（IL-10）和IL-12]和多聚免疫球蛋白（IG）受体（pIgR）（伊加和IgM的受体）的表达以及IG的分泌的影响。在B/W小鼠的颌下腺（SMG）中。断奶的B/W小鼠被喂食自由采食（AL）或补充有5%玉米油（CO）或5%鱼油（FO）的热量限制（CR）（比AL少40%的热量）饮食，直到4或9月龄。取出SMG，并将一部分组织用于IFN-γ、IL-10、IL-12（p40）和pIgR mRNA的半定量测定。将剩余的SMG组织片段化并培养7天，通过酶联免疫吸附测定法测定培养物上清液的伊加、IgM和IgG 2a水平。结果显示，在AL喂养的小鼠中，IFN-γ、IL-10和IL-12 mRNA的表达随着年龄的增长而显著增加，而CR喂养的小鼠保持其水平接近在年轻动物中观察到的水平，而与膳食脂肪无关。PIgR mRNA表达在CR动物中也保持不变，与年龄和膳食脂肪无关，而在AL喂养的小鼠中发现其显著增加。CR显着抑制伊加和IgG 2a的水平在老年小鼠中看到的升高。有趣的是，CR也影响年轻动物的IG水平。总之，这些结果表明，CR对B/W小鼠自身免疫性疾病的改善可能是通过IFN-γ、IL-10、IL-12和pIgR的mRNA表达降低以及IG分泌减少介导的。
Calorie restriction or fish oil (enriched in n-3 fatty acids) supplementation ameliorates glomerulonephritis and Sjogren's syndrome lesions in (NZB x NZW)F-1(B/W) mice. Enhanced proinflammatory cytokine expression and deposition of immune complexes are the important pathological events in the development of Sjogren's syndrome. In the present study, we have examined the effect of calorie restriction and fish oil supplementation on the expression of key inflammatory cytokines [gamma interferon (INF-gamma), interleukin-10 (IL-10), and IL-12] and polymeric immunoglobulin (Ig) receptor (pIgR) (receptor for IgA and IgM) and the secretion of Ig in the submandibular glands (SMG) of B/W mice. Weanling B/W mice were fed either ad libitum (AL) or calorie restricted (CR) (40% less calories than AL) diet supplemented with 5% corn oil (CO) or 5% fish oil (FO) until 4 or 9 months of age. The SMGs were removed and a portion of the tissue used for semiquantitive determinations of IFN-gamma, IL-10, IL-12 (p40), and pIgR mRNA. The remaining SMG tissue was fragmented and cultured for 7 days and the culture supernatants assayed for IgA, IgM, and IgG2a levels by enzyme-linked immunosorbent assay. Results revealed a significant increase in the expression of IFN-gamma, IL-10, and IL-12 mRNA with age in AL fed mice, whereas CR fed mice maintained their levels to near those seen in young animals regardless of the dietary fat. PIgR mRNA expression also remained unaltered in CR animals irrespective of age and dietary fat, while it was found significantly increased in AL fed mice. CR significantly inhibited the elevated levels of IgA and IgG2a seen in aged mice. Interestingly, CR also influenced the Ig level in young animals. In summary, these results indicate that amelioration of autoimmune disease by CR in B/W mice is possibly mediated by the lowered mRNA expression of IFN-gamma, IL-10, IL-12, and pIgR and the reduced Ig secretion.