Chandrasekar B, McGuff H S, Aufdermorte T B, Troyer D A, Talal N, Fernandes G
Department of Medicine, University of Texas Health Science Center, San Antonio 78284-7874, USA.
Clin Immunol Immunopathol. 1995 Sep;76(3 Pt 1):291-6. doi: 10.1006/clin.1995.1128.
The present study was carried out to determine whether restricting dietary calories prevents salivary gland abnormalities and modulates expression of transforming growth factor beta and proinflammatory cytokines, IL-6, and TNF alpha in major salivary glands (SG) of autoimmune lupus-prone (NZB x NZW)F1 (B/W) female mice. These mice develop focal lymphocytic interstitial and periductal round cell infiltrates in salivary glands similar to those of humans with Sjogren's syndrome. Weanling B/W mice were fed a nutritionally adequate semipurified diet either ad libitum (AL) or a calorie-restricted (CR; 40% less calories than AL) diet. The mice were sacrificed at 3.5 months (young) and 8.5 months (old) of age. Histopathologic and histomorphometric analyses as well as growth factor and cytokine protein and mRNA expression were carried out in the SG. Histomorphometric analysis of SG from young mice showed no differences between AL and CR mice, but old AL (vs old CR) had a 7.3-fold higher focus score and a 34-fold increase in percentage area inflammation. mRNA analysis revealed significantly higher levels of TGF beta 1 in SG of old CR (6.8-fold) mice. In contrast, CR reduced mRNA expression of proinflammatory cytokines (IL-6, 2.9-fold for young and 4.8-fold for old; TNF alpha, old 3.9-fold). By immunoblotting, significantly higher levels of TGF beta 1 protein was detected in old CR mice (vs old AL; 13.2-fold). IL-6 and TNF alpha proteins were undetectable in both young and old CR groups, whereas an increase in IL-6 (4.7-fold) and TNF alpha (9.3-fold) was observed in old AL mice. These results indicate that amelioration of the histological severity of disease in SG of B/W mice is paralleled and possibly mediated by increased expression of immunosuppressive TGF beta 1 and decreased expression of proinflammatory cytokines.
本研究旨在确定限制饮食热量是否能预防唾液腺异常，并调节自身免疫性狼疮易感（NZB×NZW）F1（B/W）雌性小鼠主要唾液腺（SG）中转化生长因子β以及促炎细胞因子IL-6和TNFα的表达。这些小鼠的唾液腺会出现局灶性淋巴细胞间质和导管周围圆形细胞浸润，类似于干燥综合征患者。将断乳的B/W小鼠随意喂食营养充足的半纯化饮食（AL）或热量限制（CR；比AL少40%热量）饮食。在3.5个月龄（年轻）和8.5个月龄（年老）时处死小鼠。对唾液腺进行组织病理学和组织形态计量学分析以及生长因子和细胞因子的蛋白质和mRNA表达分析。对年轻小鼠唾液腺的组织形态计量学分析显示，AL组和CR组之间无差异，但年老AL组（与年老CR组相比）的病灶评分高7.3倍，炎症面积百分比增加34倍。mRNA分析显示，年老CR组（6.8倍）小鼠唾液腺中TGFβ1水平显著更高。相比之下，CR降低了促炎细胞因子的mRNA表达（IL-6，年轻小鼠降低2.9倍，年老小鼠降低4.8倍；TNFα，年老小鼠降低3.9倍）。通过免疫印迹法检测到，年老CR组小鼠（与年老AL组相比）中TGFβ1蛋白水平显著更高（13.2倍）。在年轻和年老CR组中均未检测到IL-6和TNFα蛋白，而在年老AL组小鼠中观察到IL-6（4.7倍）和TNFα（9.3倍）增加。这些结果表明，B/W小鼠唾液腺疾病组织学严重程度的改善与免疫抑制性TGFβ1表达增加和促炎细胞因子表达降低平行，并且可能由其介导。
