FIBROBLAST INTERLEUKIN 1-BETA - SYNERGISTIC STIMULATION BY RECOMBINANT INTERLEUKIN-1 AND TUMOR NECROSIS FACTOR AND POSTTRANSCRIPTIONAL REGULATION
FIBROBLAST INTERLEUKIN 1-BETA - SYNERGISTIC STIMULATION BY RECOMBINANT INTERLEUKIN-1 AND TUMOR NECROSIS FACTOR AND POSTTRANSCRIPTIONAL REGULATION
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DOI：
10.1073/pnas.86.16.6171
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发表时间：
1989-08-01
影响因子：
11.1
通讯作者：
KERN, JA
中科院分区：
文献类型：
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作者：
ELIAS, JA;REYNOLDS, MM;KERN, JA
为了理解成纤维细胞在介导和放大炎性细胞因子的作用中所起的作用，我们确定重组白细胞介素1（IL-1）和重组肿瘤坏死因子（TNF）是否单独或组合刺激成纤维细胞产生IL-1 β。重组IL-1（α.和β）刺激的成纤维细胞IL-1 β。mRNA的积累，而重组TNF没有。此外，用重组IL-1（α.或β）和重组TNF导致IL-1 β的协同增加。mRNA水平。然而，在所有情况下，IL-1 β. mRNA积累与可溶性IL-1 β的成纤维细胞产生无关。蛋白未刺激的、重组IL-1刺激的和重组TNF刺激的成纤维细胞的裂解物不含IL-1 β。激素原相比之下，IL-1 β.在与重组IL-1和重组TNF同时孵育的成纤维细胞裂解物中检测到激素原。这些研究证明重组IL-1刺激成纤维细胞IL-1 β。mRNA积累以及重组IL-1和重组TNF协同作用以进一步上调IL-1 β。mRNA水平。此外，他们显示IL-1 β.人肺成纤维细胞的产生在转录后水平受到抑制。翻译控制似乎是重要的重组IL-1刺激的成纤维细胞和翻译后控制是重要的，同时刺激重组IL-1和重组TNF的成纤维细胞。
To understand the role fibroblasts play in mediating and amplifying the effects of inflammatory cytokines, we determined whether recombinant interleukin 1 (IL-1) and recombinant tumor necrosis factor (TNF), alone and in combination, stimulated fibroblasts to produce IL-1.beta.. Recombinant IL-1 (.alpha. and .beta.) stimulated fibroblast IL-1.beta. mRNA accumulation, whereas recombinant TNF did not. In addition, simultaneous stimulation with recombinant IL-1 (.alpha. or .beta.) and recombinant TNF resulted in a synergistic increase in IL-1.beta. mRNA levels. However, in all cases, IL-1.beta. mRNA accumulation was not associated with fibroblast production of soluble IL-1.beta. protein. Lysates of unstimulated, recombinant IL-1-stimulated, and recombinant TNF-stimulated fibroblasts did not contain IL-1.beta. prohormone. In contrast, IL-1.beta. prohormone was detected in lysates of fibroblasts incubated simultaneously with recombinant IL-1 and recombinant TNF. These studies demonstrate that recombinant IL-1 stimulates fibroblast IL-1.beta. mRNA accumulation and that recombinant IL-1 and recombinant TNF synergize to further up-regulate IL-1.beta. mRNA levels. In addition, they show that IL-1.beta. production by human lung fibroblasts is inhibited at a posttranscriptional level. Translational control appears to be important in recombinant IL-1-stimulated fibroblasts and posttranslational control is important in fibroblasts stimulated simulataneously with recombinant IL-1 and recombinant TNF.