Dexamethasone inhibits the induction of monocyte chemotactic-activating factor production by IL-1 or tumor necrosis factor.
Dexamethasone inhibits the induction of monocyte chemotactic-activating factor production by IL-1 or tumor necrosis factor.
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DOI：
10.4049/jimmunol.146.4.1212
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发表时间：
1991-02
影响因子：
4.4
通讯作者：
N. Mukaida;C. Zachariae;G. Gusella;Koji Matsushima
中科院分区：
文献类型：
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作者：
N. Mukaida;C. Zachariae;G. Gusella;Koji Matsushima
最近纯化和分子克隆的单核细胞趋化激活因子(MCAF)可能在炎症过程中募集和激活单核细胞中发挥重要作用。我们研究了一种有效的抗炎药地塞米松(DXS)对该因子产生的影响。在较宽的浓度范围内(10(-5)~10(-8)M)，DXS在IL-1或TNF-α刺激的人纤维肉瘤细胞系中，在mRNA和蛋白水平上抑制MCAF的产生。我们检测了合成的MCAF mRNA的翻转，显示DXS降低了MCAF mRNA的稳定性。此外，放线菌素D和放线菌亚胺的加入取消了DXS的这种作用，表明这一过程需要从头合成mRNA和蛋白质。此外，核径流分析显示，DXS还抑制IL-1或肿瘤坏死因子激活的MCAF基因的转录。因此，MCAF mRNA的失稳和基因转录的抑制都是DXS降低MCAF mRNA稳态水平的原因之一。
Recently purified and molecularly cloned monocyte chemotactic and activating factor (MCAF) may play a major role in recruiting and activating monocytes in the inflammatory process. We examined the effects of a potent anti-inflammatory agent, dexamethasone (DXS), on the production of this factor. Over a wide range of concentrations (10(-5) to 10(-8) M), DXS inhibited the production of MCAF at the mRNA and protein level in a human fibrosarcoma cell line, which was stimulated with either IL-1 or TNF-alpha. We examined the turn-over of synthesized MCAF mRNA that showed DXS decreased the stability of MCAF mRNA. Furthermore, the addition of actinomycin D and cycloheximide abolished this effect of DXS, indicating that de novo mRNA and protein synthesis were required for this process. In addition, a nuclear run-off analysis revealed that DXS also inhibited the transcription of IL-1- or TNF-activated MCAF genes. Therefore, both the destabilization of MCAF mRNA and the inhibition of transcription of the gene contribute to the decrease in the MCAF mRNA steady state level by DXS.