α-Melanocyte-Stimulating Hormone Inhibits the Nuclear Transcription Factor NF-κB Activation Induced by Various Inflammatory Agents
α-Melanocyte-Stimulating Hormone Inhibits the Nuclear Transcription Factor NF-κB Activation Induced by Various Inflammatory Agents
复制标题
α-黑素细胞刺激激素抑制各种炎症因子诱导的核转录因子 NF-κB 激活
作者：
S. Manna;B. Aggarwal
α-促黑素细胞激素（α-MSH）是一种十三肽，主要存在于脑、垂体和循环中。它通过一种未知的机制抑制大多数形式的炎症。由于大多数类型的炎症需要NF-κB的激活，我们研究了α-MSH对多种炎症刺激物激活该转录因子的影响。电泳迁移率改变实验显示，α-MSH可完全阻断TNF介导的NF-κB活化，并呈剂量和时间依赖性。它还抑制LPS、冈田酸和神经酰胺诱导的NF-κB活化。该效应是特异性的，因为TNF对转录因子激活蛋白-1的激活不受影响。Western blot分析显示，TNF依赖的NF-κB抑制亚基、IκBα的降解以及NF-κB p65亚基的核转位也受到抑制。这与TNF诱导的NF-κ B依赖性报告基因表达的抑制有关。α-MSH的抑制作用似乎是通过cAMP的产生介导的，因为腺苷酸环化酶和蛋白激酶A的抑制剂逆转了其抑制作用。类似地，加入膜可渗透的二丁酰cAMP，如α-MSH，抑制TNF诱导的NF-κB活化。总之，我们的研究结果表明，α-MSH抑制NF-κB激活的各种炎症介质，这一机制可能有助于其抗炎作用。
α-Melanocyte-stimulating hormone (α-MSH) is a tridecapeptide found mainly in the brain, pituitary, and circulation. It inhibits most forms of inflammation by a mechanism that is not known. As most types of inflammation require activation of NF-κB, we investigated the effect of α-MSH on the activation of this transcription factor by a wide variety of inflammatory stimuli. Electrophoretic mobility shift assay showed that α-MSH completely abolished TNF-mediated NF-κB activation in a dose- and time-dependent manner. It also suppressed NF-κB activation induced by LPS, okadaic acid, and ceramide. The effect was specific, as the activation of the transcription factor activating protein-1 by TNF was unaffected. Western blot analysis revealed that TNF-dependent degradation of the inhibitory subunit of NF-κB, IκBα, and nuclear translocation of the p65 subunit of NF-κB were also inhibited. This correlated with suppression of NF-κB-dependent reporter gene expression induced by TNF. The inhibitory effect of α-MSH appeared to be mediated through generation of cAMP, as inhibitors of adenylate cyclase and of protein kinase A reversed its inhibitory effect. Similarly, addition of membrane-permeable dibutyryl cAMP, like α-MSH, suppressed TNF-induced NF-κB activation. Overall, our results suggest that α-MSH suppresses NF-κB activated by various inflammatory agents and that this mechanism probably contributes to its anti-inflammatory effects.
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影响因子：
2.9
作者：
H. Hassanain;W. Dai;S. Gupta
通讯作者：
H. Hassanain;W. Dai;S. Gupta
影响因子：
5.8
作者：
K. W. Kelley
通讯作者：
K. W. Kelley
生长激素对脂多糖刺激的人单核细胞中 TNF-α 分泌和核因子-κB 易位的抑制作用。
DOI：
--
发表时间：
1997
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Haeffner,A;Thieblemont,N;Déas,O;Marelli,O;Charpentier,B;Senik,A;Wright,SD;Haeffner-Cavaillon,N;Hirsch,F
通讯作者：
Hirsch,F
影响因子：
11.4
作者：
NEUMANN, M;GRIESHAMMER, T;SERFLING, E
通讯作者：
SERFLING, E
DOI：
10.1016/s0021-9258(18)53088-x
发表时间：
1993-04
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
I. Gantz;Y. Konda;T. Tashiro;Y. Shimoto;Hiroto Miwa;G. Munzert;S. Watson;J. Delvalle;Thoru Yamada
通讯作者：
I. Gantz;Y. Konda;T. Tashiro;Y. Shimoto;Hiroto Miwa;G. Munzert;S. Watson;J. Delvalle;Thoru Yamada