TUMOR NECROSIS FACTOR INTERACTS WITH INTERLEUKIN-1 AND INTERFERONS TO INHIBIT FIBROBLAST PROLIFERATION VIA FIBROBLAST PROSTAGLANDIN-DEPENDENT AND PROSTAGLANDIN-INDEPENDENT MECHANISMS
TUMOR NECROSIS FACTOR INTERACTS WITH INTERLEUKIN-1 AND INTERFERONS TO INHIBIT FIBROBLAST PROLIFERATION VIA FIBROBLAST PROSTAGLANDIN-DEPENDENT AND PROSTAGLANDIN-INDEPENDENT MECHANISMS
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DOI：
10.1164/ajrccm/138.3.652
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发表时间：
1988-09-01
期刊：
影响因子：
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通讯作者：
ELIAS, JA
中科院分区：
文献类型：
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作者：
ELIAS, JA
单核细胞是成纤维细胞功能的重要调节者。然而，介导这些影响的可溶性因子和这些调节事件中细胞因子间相互作用的重要性仍然知之甚少。我们分析了重组（r）白细胞介素-1-α的作用。（IL-1）、肿瘤坏死因子（TNF）和γ，α，和β 1干扰素（IFN）单独和组合对正常人肺成纤维细胞增殖的影响。rIL-1和rTNF弱刺激成纤维细胞增殖，而rIFN抑制成纤维细胞增殖。重要的是，当rTNF与rIL-1或rIFN组合时，注意到成纤维细胞增殖的协同抑制。由rINF-γ引起的抑制加rTNF在很大程度上不依赖于成纤维细胞前列腺素（PG）的产生，因为在这些细胞因子存在下成纤维细胞PG水平不变，并且阻断成纤维细胞PG的产生不会改变它们的抑制作用。相反，由rIL-1加rTNF引起的抑制似乎至少部分由成纤维细胞PG产生介导，因为这些细胞因子协同作用以刺激成纤维细胞PG产生，并且阻断成纤维细胞PG产生逆转了它们引起的抑制。这些研究表明，TNF可以与IL-1或IFN相互作用，以抑制正常二倍体成纤维细胞的增殖，这些细胞因子组合的抑制作用是由不同的机制介导的。
Mononuclear cells are important regulators of fibroblast function. However, the soluble factors mediating these effects and the importance of intercytokine interactions in these regulating events remain poorly understood. We analyzed the effect of recombinant (r) interleukin-1-.alpha. (Il-1), tumor necrosis factor (TNF), and .gamma., .alpha., and .beta.1 interferons (IFN), alone and in combination, on the proliferation of normal human lung fibroblasts. rIL-1 and rTNF weakly stimulated and the rIFNs inhibited fibroblast proliferation. Importantly, when rTNF was combined with rIL-1 or rIFN, synergistic inhibition of fibroblast proliferation was noted. The inhibition caused by rINF-.gamma. plus rTNF was largely independent of fibroblast prostaglandin (PG) production because fibroblast PG levels were unaltered in the presence of these cytokines and blocking fibroblast PG production did not alter their inhibitory effect. In contrast, the inhibition caused by rIL-1 plus rTNf appeared to be at least partially mediated by fibroblast PG production because these cytokines acted synergistically to stimulate fibroblast PG production and blocking fibroblast PG production reversed the inhibition that they caused. These studies demonstrate that TNF can interact with IL-1 or IFN to inhibit the proliferation of normal diploid fibroblasts and that the inhibitory effects of these cytokine combinations are mediated by different mechanisms.