Enhancement of cAMP levels and of protein kinase activity by tumor necrosis factor and interleukin 1 in human fibroblasts: role in the induction of interleukin 6.
Enhancement of cAMP levels and of protein kinase activity by tumor necrosis factor and interleukin 1 in human fibroblasts: role in the induction of interleukin 6.
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肿瘤坏死因子和白细胞介素 1 在人成纤维细胞中增强 cAMP 水平和蛋白激酶活性：在诱导白细胞介素 6 中的作用。
DOI：
10.1073/pnas.85.18.6802
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发表时间：
1988
影响因子：
11.1
通讯作者：
Vilcek,J
中科院分区：
文献类型：
--
作者：
Zhang,YH;Lin,JX;Yip,YK;Vilcek,J
虽然肿瘤坏死因子（TNF）和白细胞介素1（IL-1）影响许多细胞功能，但TNF和IL-1作用的分子机制尚不清楚。我们目前的研究表明，人FS-4成纤维细胞暴露于TNF或IL-1引起细胞内cAMP的快速积累和蛋白激酶活性的增加。细胞内cAMP水平达到峰值3-5分钟后，加入TNF或IL-1和恢复到基础水平的15分钟。增加组蛋白HII-B蛋白的磷酸化证明与制备的提取物TNF-或IL-1处理的细胞，表明cAMP依赖性蛋白激酶活性的增加。没有证据表明，蛋白激酶C激活TNF-处理的FS-4细胞。TNF、IL-1和forskolin均刺激FS-4细胞中白细胞介素6（IL-6）mRNA水平。蛋白激酶抑制剂H-8优先抑制cAMP依赖性激酶活性，降低毛喉素刺激的IL-6 mRNA诱导比TNF-或IL-1驱动的IL-6 mRNA诱导更强烈。这些结果表明，激活cAMP依赖性蛋白激酶的TNF和IL-1是重要的，在这些细胞因子的一些行动。此外，我们的数据IL-6诱导TNF和IL-1表明，其他尚未确定的信号转导机制有助于TNF和IL-1对人成纤维细胞基因表达的作用。
Although tumor necrosis factor (TNF) and interleukin 1 (IL-1) affect many cell functions, the molecular mechanisms of TNF and IL-1 action are not understood. Our present study shows that exposure of human FS-4 fibroblasts to TNF or IL-1 caused a rapid accumulation of intracellular cAMP and an increase in protein kinase activity. Intracellular cAMP levels peaked 3-5 min after the addition of TNF or IL-1 and returned to basal level by 15 min. Increased phosphorylation of histone HII-B protein was demonstrated with extracts prepared from TNF- or IL-1-treated cells, suggesting an increase in cAMP-dependent protein kinase activity. No evidence was obtained for protein kinase C activation in TNF-treated FS-4 cells. TNF, IL-1, and forskolin all stimulated interleukin 6 (IL-6) mRNA levels in FS-4 cells. The protein kinase inhibitor H-8, inhibiting preferentially cAMP-dependent kinase activity, reduced forskolin-stimulated IL-6 mRNA induction more strongly than TNF- or IL-1-driven IL-6 mRNA induction. These results suggest that activation of cAMP-dependent protein kinase by TNF and IL-1 is important in some actions of these cytokines. In addition, our data on IL-6 induction by TNF and IL-1 suggest that other, yet unidentified, signal transduction mechanisms contribute to TNF and IL-1 actions on gene expression in human fibroblasts.