Contrasting mechanisms for suppression of macrophage cytokine release by transforming growth factor-beta and interleukin-10.
Contrasting mechanisms for suppression of macrophage cytokine release by transforming growth factor-beta and interleukin-10.
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DOI：
10.1016/s0021-9258(18)50091-0
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发表时间：
1992-11
期刊：
影响因子：
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通讯作者：
C. Bogdan;J. Paik;Y. Vodovotz;C. Nathan
中科院分区：
文献类型：
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作者：
C. Bogdan;J. Paik;Y. Vodovotz;C. Nathan
转化生长因子（TGF）-β和白细胞介素（IL）-10通过对比转录后机制抑制脂多糖（LPS）诱导的巨噬细胞产生炎性细胞因子肿瘤坏死因子-α（TNF）、IL-1 α和IL-1 β。TGF-β作用缓慢且延迟，因为它需要12-16 h才能发挥抑制作用，并且即使在LPS后6 h加入也能抑制TNF产生。TGF-β既不影响TNF mRNA的水平，也不影响TNF的释放和降解。因此，TGF-β似乎抑制TNF mRNA的翻译。IL-10不仅抑制TNF释放的程度比TGF-β高25倍，而且还抑制IL-1的释放。与TGF-β相反，IL-10作用于细胞因子产生的早期步骤，其作用在加入LPS后3小时最大。与TGF-β不同，IL-10显著抑制TNF、IL-1 α和IL-1 β mRNA水平。然而，这是在不抑制相应基因转录的情况下完成的。此外，放线菌酮拮抗IL-10依赖性细胞因子mRNA水平的降低。因此，IL-10可以诱导对细胞因子转录物有活性的核糖核酸酶，或者可以诱导增强TNF、IL-1 α和IL-1 β mRNA对核糖核酸溶解作用的易感性的蛋白质。我们得出结论，IL-10和TGF-β诱导不同的巨噬细胞失活表型，并通过不同的机制使巨噬细胞失活：IL-10促进细胞因子mRNA的降解，而TGF-β主要抑制翻译。
Transforming growth factor (TGF)-beta and interleukin (IL)-10 inhibited lipopolysaccharide (LPS)-induced macrophage production of the inflammatory cytokines tumor necrosis factor-alpha (TNF), IL-1 alpha, and IL-1 beta by contrasting post-transcriptional mechanisms. TGF-beta acted slowly and late, as it required 12-16 h to exert a suppressive effect, and inhibited TNF production even when added 6 h after LPS. TGF-beta affected neither the level of TNF mRNA, the release of preformed TNF nor the degradation of TNF. Thus, TGF-beta appeared to inhibit translation of TNF mRNA. IL-10 not only suppressed TNF release to a 25-fold greater extent than TGF-beta, but also inhibited release of IL-1. In contrast to TGF-beta, IL-10 acted on an early step in cytokine production, its effect being maximal 3 h after addition of LPS. Unlike TGF-beta, IL-10 markedly suppressed TNF, IL-1 alpha, and IL-1 beta mRNA levels. However, this was accomplished without suppressing transcription of the corresponding genes. Moreover, cycloheximide antagonized the IL-10-dependent reduction in cytokine mRNA levels. Thus, IL-10 may induce a ribonuclease active on cytokine transcripts or may induce a protein that enhances the susceptibility of TNF, IL-1 alpha, and IL-1 beta mRNAs to ribonucleolytic action. We conclude that IL-10 and TGF-beta induce different phenotypes of macrophage deactivation, and deactivate macrophages by different mechanisms: IL-10 promotes degradation of cytokine mRNA, while TGF-beta primarily suppresses translation.