Boswell J M, Yui M A, Endres S, Burt D W, Kelley V E
Laboratory of Immunogenetics and Transplantation, Brigham and Women's Hospital, Boston, MA 02115.
J Immunol. 1988 Jul 1;141(1):118-24.
IL-1 is a pleiotropic factor encoded for by at least two genes, alpha and beta, and capable of eliciting a broad set of immunologic and inflammatory events. MRL/MP-lpr (MRL-lpr) mice are an appealing model for studies of renal injury inasmuch as disease in this strain is spontaneous, rapid, predictable, and regulated by the lpr gene. Infiltration of macrophages and the proliferation of the glomerular mesangial cells are prominent features of renal disease. Because both mesangial cells and macrophages can synthesize IL-1, the purpose of this study was to determine whether enhanced IL-1 gene expression is associated with lupus nephritis in the MRL-lpr mouse model. Glomerular macrophages, abundant in the kidneys of MRL-lpr mice but rarely present in the kidney of congenic MRL/MP-++(MRL-++) mice, were isolated and cultured and found to express a 10-fold increase in both IL-1 alpha and IL-1 beta mRNA transcripts as compared with MRL-++ and MRL-lpr mesangial cells. IL-1 alpha was not detected in the total RNA extracted from freshly excised kidney, whereas IL-1 beta transcripts were detected in both the renal cortex of MRL-lpr as well as MRL-++ animals. A previously undetected truncated 1200 nucleotide IL-1 beta transcript together with the conventional 1600 nucleotide IL-1 beta transcript was found in kidneys from MRL-lpr and was abundantly expressed in glomeruli of MRL-lpr mice with lupus nephritis. Isolated glomeruli from MRL-lpr mice with nephritis produce IL-1, whereas in normal glomeruli from MRL-++ and C3H/FeJ mice this cytokine was not detected. Glomerular macrophages and mesangial cells cultured from MRL-lpr mice with nephritis both secrete IL-1. These studies indicate that IL-1 beta gene expression and IL-1 protein are increased in the kidneys of autoimmune mice with lupus nephritis and is generated, at least in part, by glomerular macrophages. We speculate that an alteration in IL-1 beta gene expression may be responsible for causing a cascade of events leading to acute and chronic renal injury.
白细胞介素 -1（IL-1）是一种多效性因子，由至少两个基因（α和β）编码，能够引发一系列广泛的免疫和炎症反应。MRL/MP-lpr（MRL-lpr）小鼠是研究肾损伤的一个有吸引力的模型，因为该品系的疾病是自发的、快速的、可预测的，并且受lpr基因调控。巨噬细胞浸润和肾小球系膜细胞增殖是肾脏疾病的突出特征。由于系膜细胞和巨噬细胞都能合成IL-1，本研究的目的是确定IL-1基因表达增强是否与MRL-lpr小鼠模型中的狼疮性肾炎相关。从MRL-lpr小鼠肾脏中分离出丰富但在同基因MRL/MP-++（MRL-++）小鼠肾脏中很少出现的肾小球巨噬细胞，进行培养后发现，与MRL-++和MRL-lpr系膜细胞相比，其IL-1α和IL-1β mRNA转录本增加了10倍。从新鲜切除的肾脏中提取的总RNA中未检测到IL-1α，而在MRL-lpr以及MRL-++动物的肾皮质中均检测到了IL-1β转录本。在MRL-lpr小鼠的肾脏中发现了一种先前未检测到的截短的1200个核苷酸的IL-1β转录本以及传统的1600个核苷酸的IL-1β转录本，并且在患有狼疮性肾炎的MRL-lpr小鼠的肾小球中大量表达。患有肾炎的MRL-lpr小鼠分离出的肾小球产生IL-1，而在MRL-++和C3H/FeJ小鼠的正常肾小球中未检测到这种细胞因子。从患有肾炎的MRL-lpr小鼠培养的肾小球巨噬细胞和系膜细胞都分泌IL-1。这些研究表明，患有狼疮性肾炎的自身免疫小鼠肾脏中IL-1β基因表达和IL-1蛋白增加，并且至少部分由肾小球巨噬细胞产生。我们推测，IL-1β基因表达的改变可能是导致一系列导致急性和慢性肾损伤事件的原因。
