Zoja C, Bettoni S, Morigi M, Remuzzi G, Rambaldi A
Mario Negri Institute for Pharmacological Research, Ospedali Riuniti di Bergamo, Italy.
J Am Soc Nephrol. 1992 Jun;2(12):1709-15. doi: 10.1681/ASN.V2121709.
We have recently shown that interleukin-1 is a potent stimulus of gene expression and production of leukocyte chemotactic factors, colony-stimulating factors, and interleukin-6 in human mesangial cells in culture. Here, we sought to determine whether interleukin-1 induces its own gene expression in human mesangial cells. Interleukin-1 mRNA levels were quantitated by Northern blot analysis with total cellular RNAs isolated from human mesangial cells exposed for 6 h to medium alone or in the presence of human recombinant interleukin-1 beta (1 to 100 ng/mL). Interleukin-1 induced interleukin-1 mRNA expression in a dose-dependent manner. An additional finding of this study was that human mesangial cells constitutively express the 80 kd interleukin-1 receptor type 1 gene. When human mesangial cells were exposed to interleukin-1, interleukin-1 receptor expression was not modified. Similarly, other stimuli like tumor necrosis factor, transforming growth factor beta, or interleukin-6 did not modulate interleukin-1 receptor expression. Recombinant interleukin-1 receptor antagonist blocked the interleukin-1 mRNA as well as interleukin-6 and interleukin-8 mRNA accumulation induced by interleukin-1 beta. Lipopolysaccharide, which is a known stimulus for interleukin-1 transcription in several cell types, also induced interleukin-1 mRNA accumulation, thus indicating that lipopolysaccharide mediates interleukin-1 gene activation in human mesangial cells through an interleukin-1-independent pathway. These data support the pivotal role of interleukin-1 in regulating mesangial cell cytokine genes and may be taken to indicate the existence of an interleukin-1-mediated positive feedback loop that might control the secretion of active cytokines within the glomeruli when an immunological or inflammatory injury takes place.
我们最近发现，白细胞介素-1是培养的人系膜细胞中基因表达以及白细胞趋化因子、集落刺激因子和白细胞介素-6产生的有效刺激物。在此，我们试图确定白细胞介素-1是否在人系膜细胞中诱导其自身的基因表达。通过Northern印迹分析对白细胞介素-1 mRNA水平进行定量，所用的总细胞RNA是从单独暴露于培养基6小时或在存在人重组白细胞介素-1β（1至100 ng/mL）的情况下的人系膜细胞中分离得到的。白细胞介素-1以剂量依赖的方式诱导白细胞介素-1 mRNA表达。本研究的另一项发现是，人系膜细胞组成性表达80 kd的1型白细胞介素-1受体基因。当人系膜细胞暴露于白细胞介素-1时，白细胞介素-1受体的表达未发生改变。同样，其他刺激物如肿瘤坏死因子、转化生长因子β或白细胞介素-6也未调节白细胞介素-1受体的表达。重组白细胞介素-1受体拮抗剂可阻断白细胞介素-1β诱导的白细胞介素-1 mRNA以及白细胞介素-6和白细胞介素-8 mRNA的积累。脂多糖是几种细胞类型中白细胞介素-1转录的已知刺激物，它也诱导白细胞介素-1 mRNA的积累，这表明脂多糖通过一条不依赖白细胞介素-1的途径介导人系膜细胞中白细胞介素-1基因的激活。这些数据支持白细胞介素-1在调节系膜细胞细胞因子基因方面的关键作用，并可能表明存在一个白细胞介素-1介导的正反馈环，当发生免疫或炎症损伤时，该反馈环可能控制肾小球内活性细胞因子的分泌。
