LIPOPOLYSACCHARIDE INDUCES HUMAN INTERLEUKIN-1 RECEPTOR ANTAGONIST AND INTERLEUKIN-1 PRODUCTION IN THE SAME CELL
LIPOPOLYSACCHARIDE INDUCES HUMAN INTERLEUKIN-1 RECEPTOR ANTAGONIST AND INTERLEUKIN-1 PRODUCTION IN THE SAME CELL
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DOI：
10.1002/eji.1830221022
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发表时间：
1992-10-01
影响因子：
5.4
通讯作者：
ANDERSSON, U
中科院分区：
文献类型：
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作者：
ANDERSSON, J;BJORK, L;ANDERSSON, U
最近描述了白细胞介素-1 (IL-1) 家族的一个新成员。人 IL-1 受体拮抗剂 (IL-1ra) 在结构上与 IL-1α 和 IL-1β 相关，但与各种靶细胞上的 IL-1 受体结合，但没有明显的激动剂活性。了解 IL-1ra 产生的调节机制可以阐明这种独特细胞因子的生物学特性，并阐明其作为天然抗炎蛋白的可能作用。通过使用细胞因子特异性抗体和间接免疫荧光技术，在单细胞水平上研究了脂多糖 (LPS) 对 IL-1α、IL-1β 和 IL-1ra 产生的影响。从健康献血者获得的外周血单核细胞中，IL-1ra 和 IL-1α/β 的合成峰值分别发生在细胞刺激后 4 小时和 6 小时内。通过双重染色程序，所有 IL-1ra 阳性细胞也是 IL-1α 和/或 β 阳性。因此，内毒素诱导同一细胞中IL-1基因家族的同时合成。在细胞培养 96 小时期间，只有单核细胞有助于产生 IL-1α、β 和 IL-1ra。产生IL-1ra的单核细胞的最大数量为48+/-16%，而IL-1α和β的峰值产生分别为所有外周血单核细胞的75+/-9%和80+/-12%(p<0.001)。含有IL-1α和β的细胞的发生率不仅显着更高，而且发生的时间更长，与位于高尔基体细胞器的IL-1ra的24小时相比，为72小时。然而，在刺激后 12 至 72 小时的后期阶段，具有弥漫性细胞质外观的含有 IL-1ra 的细胞也很明显 (20%-30%)。在刺激前添加外源重组IL-1β来阻断IL-1表面受体不能抑制弥漫性胞质定位。这表明“晚期”染色模式并不反映IL-1ra在与细胞外受体结合后被分泌和内化。因此，也许IL-1ra通过细胞内外的受体相互作用来调节IL-1效应机制。
A new member of the interleukin-1 (IL-1) family has recently been described. Human IL-1 receptor antagonist (IL-1ra) is structurally related to IL-1alpha and IL-1beta but binds to IL-1 receptors on various target cells without demonstrable agonist activity. Understanding the mechanisms of regulation of IL-1ra production may clarify the biology of this unique cytokine as well as elucidate its possible role as a natural anti-inflammatory protein. The effects of lipopolysaccharide (LPS) on IL-1alpha, IL-1beta and IL-1ra production was studied at a single-cell level by use of cytokine-specific antibodies and indirect immunofluorescence technique. The peak synthesis of IL-1ra and IL-1alpha/beta occurred in peripheral blood monocytes obtained from healthy blood donors within 4 and 6 h of cell stimulation, respectively. By double-staining procedure all IL-1ra-positive cells were also IL-1alpha and/or beta positive. Thus, endotoxin induced simultaneous synthesis of the IL-1 gene family in the same cells. Only monocytes contributed to the production of IL-1alpha, beta and IL-1ra during the 96 h of cell culture. The maximum number of IL-Ira-producing monocytes was 48 +/- 16% as compared to peak production of IL-1alpha and beta which occurred in 75 +/- 9% and 80 +/- 12% (p < 0.001), respectively, of all peripheral blood monocytes. The incidence of IL-1alpha- and beta-containing cells was not only significantly higher but also occurred for a longer time period, 72 h as compared to 24 h for IL-1ra localized in the Golgi organelle. However, IL-1ra-containing cells with a diffuse cytoplasmic appearance were also evident (20%-30%) at a later stage, 12 to 72 h after stimulation. Blocking IL-1 surface receptors by addition of exogenous recombinant IL-1beta before stimulation could not inhibit the diffuse cytosolic localization. This indicates that the "late" staining pattern did not reflect IL-1ra being secreted and internalized after binding to extracellular receptors. Thus, perhaps IL-Ira modulates IL-1 effector mechanisms by receptor interactions both inside and outside the cell.