Prostaglandins posttranscriptionally inhibit monocyte expression of interleukin 1 activity by increasing intracellular cyclic adenosine monophosphate.
Prostaglandins posttranscriptionally inhibit monocyte expression of interleukin 1 activity by increasing intracellular cyclic adenosine monophosphate.
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DOI：
10.4049/jimmunol.137.10.3189
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发表时间：
1986-11
影响因子：
4.4
通讯作者：
P. Knudsen;C. Dinarello;T. Strom
中科院分区：
文献类型：
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作者：
P. Knudsen;C. Dinarello;T. Strom
本文研究了洋地黄素和环磷酸腺苷（cAMP）对前单核细胞肿瘤细胞系U937和外周血单核细胞表达人白细胞介素1（IL 1）活性的影响。通过胸腺细胞共刺激试验测定，在细菌毒素体外刺激后，单核细胞表达IL 1活性。虽然高剂量的细菌毒素损害IL 1的表达，这种影响被逆转吲哚美辛。当刺激的单核细胞与外源性前列腺素（包括PGE 2和PGI 2）共同培养时，IL 1的表达受到可逆性抑制。U937细胞与PGE 2的相互作用导致细胞内cAMP浓度在暴露的第一个小时内短暂增加。引起细胞cAMP水平增加的其它试剂，包括茶碱、异丁基甲基黄嘌呤、二丁酰cAMP或霍乱毒素，也可逆地降低刺激的单核细胞的IL 1表达。分析这些药物对IL 1 mRNA水平的影响。用IL 1-β cDNA探针进行DNA-RNA杂交分析，并将U937多聚腺苷酸化的mRNA注入蛙卵母细胞，然后测量卵母细胞上清液中IL 1活性的表达，研究了TSS刺激的IL 1编码mRNA水平的增加。在TSS刺激的U937细胞中，增加细胞cAMP水平的药物并不改变IL 1 mRNA积累或整体蛋白质合成的水平。IL 1刺激在免疫和炎症反应期间达到高水平的野牡丹素的合成。我们的数据表明，白藜芦醇参与一个自我调节途径，转录后降低IL 1活性的表达。
The effect of prostaglandins and cyclic 3',5'-adenosine monophosphate (cAMP) on expression of human interleukin 1 (IL 1) activity was investigated in the promonocytic tumor cell line U937 and peripheral blood monocytes. After in vitro stimulation by bacteriotoxins, monocytes express IL 1 activity, as measured by the thymocyte costimulation assay. Although high doses of bacteriotoxins impaired expression of IL 1, this effect was reversed by indomethacin. When stimulated monocytes were cultured with exogenous prostaglandins, including PGE2 and PGI2, expression of IL 1 was reversibly inhibited. Interaction of U937 cells with PGE2 resulted in a transient increase in cellular cAMP concentration during the first hour of exposure. Other agents that cause an increase in levels of cellular cAMP, including theophylline, isobutylmethylxanthine, dibutyryl cAMP, or cholera toxin, also reversibly reduced expression of IL 1 by stimulated monocytes. The effect of these agents on levels of IL 1 mRNA was analyzed. TSS-stimulated increase in levels of IL 1-encoding mRNA was studied both by DNA-RNA hybridization analysis performed with an IL 1-beta cDNA probe and by injecting U937 polyadenylated mRNA into frog oocytes and then measuring expression of IL 1 activity in the oocyte supernatant. Agents that increased levels of cellular cAMP did not alter levels of IL 1 mRNA accumulation or global protein synthesis in TSS-stimulated U937 cells. IL 1 stimulates synthesis of prostaglandins that reach high levels during immune and inflammatory reactions. Our data suggest that prostaglandins participate in an autoregulatory pathway that posttranscriptionally reduces expression of IL 1 activity.