Boswell J M, Yui M A, Burt D W, Kelley V E
Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115.
J Immunol. 1988 Nov 1;141(9):3050-4.
Because TNF and IL-1 can initiate immunologic and inflammatory events alone or synergistically, a local increase in the levels of one or both of these cytokines in vivo may cause irreparable tissue damage. The purpose of this study was to evaluate local TNF and IL-1 beta gene expression in vivo in the kidneys of MRL-Ipr mice with autoimmune lupus nephritis. TNF mRNA was detected in the renal cortex of MRL-Ipr mice but was not present in the cortex of normal congenic MRL-++ or C3H/FeJ mice. MRL-Ipr mice with lupus nephritis expressed higher amounts of TNF mRNA compared with MRL-Ipr mice prior to disease. In addition, freshly isolated, unstimulated glomeruli from MRL-Ipr mice with nephritis were found to secrete detectable levels of TNF, whereas glomeruli from MRL-++ mice did not. IL-1 beta mRNA, present in the renal cortex of C3H/FeJ, MRL-++, and young MRL-Ipr mice with normal kidneys, was also more abundantly expressed in MRL-Ipr mice with nephritis. Cultured macrophages from glomeruli of mice with nephritis were found to express TNF and IL-1 beta mRNA and product. These macrophages are prominent only in MRL-Ipr mice with renal disease and are the likely source of increased gene expression for both cytokines.
由于肿瘤坏死因子（TNF）和白细胞介素-1（IL-1）可单独或协同引发免疫和炎症反应，体内这两种细胞因子中一种或两种水平的局部升高可能会导致无法修复的组织损伤。本研究的目的是评估自身免疫性狼疮性肾炎MRL-Ipr小鼠肾脏中TNF和IL-1β基因在体内的局部表达情况。在MRL-Ipr小鼠的肾皮质中检测到TNF mRNA，但在正常同基因MRL-++或C3H/FeJ小鼠的皮质中未检测到。与疾病发生前的MRL-Ipr小鼠相比，患有狼疮性肾炎的MRL-Ipr小鼠表达更高量的TNF mRNA。此外，发现来自患有肾炎的MRL-Ipr小鼠的新鲜分离的未受刺激的肾小球分泌可检测水平的TNF，而来自MRL-++小鼠的肾小球则不分泌。IL-1βmRNA存在于C3H/FeJ、MRL-++以及肾脏正常的年轻MRL-Ipr小鼠的肾皮质中，在患有肾炎的MRL-Ipr小鼠中也有更丰富的表达。发现来自患有肾炎小鼠肾小球的培养巨噬细胞表达TNF和IL-1βmRNA及产物。这些巨噬细胞仅在患有肾脏疾病的MRL-Ipr小鼠中显著存在，并且可能是这两种细胞因子基因表达增加的来源。
