Sung S S, Walters J A
Department of Radiation Oncology, Medical College of Virginia, Virginia Commonwealth University, Richmond 23298.
J Clin Invest. 1991 Dec;88(6):1915-23. doi: 10.1172/JCI115515.
The effects of increasing intracellular cAMP levels on IL-1 alpha and IL-1 beta mRNA expression and IL-1 production in human monocytes and nonlymphoid hematopoietic cell lines were examined. Peripheral monocytes and myelomonocytic cell lines could be stimulated by LPS or phorbol myristate acetate (PMA) to express IL-1 mRNA. Dibutyryl cAMP, 8-bromo-cAMP, forskolin, cholera toxin, PGE1, and PGE2 synergized with PMA or LPS to increase the accumulation in cell lines of IL-1 alpha mRNA by up to 50-fold and that of IL-1 beta mRNA by 10- to 20-fold compared to LPS or PMA alone. This increase in IL-1 alpha and IL-1 beta mRNA accumulation was more modest in monocytes. The synergistic stimulation was due to enhanced IL-1 gene transcription rate rather than increased IL-1 mRNA stability. Despite this marked increase in IL-1 mRNA accumulation, IL-1 protein synthesis in these cells was increased by only twofold. Thus, IL-1 synthesis in monocytes and myelomonocytic cell lines is under stringent translational control.
研究了细胞内cAMP水平升高对人单核细胞和非淋巴细胞造血细胞系中IL-1α和IL-1β mRNA表达及IL-1产生的影响。外周单核细胞和骨髓单核细胞系可被脂多糖(LPS)或佛波酯(PMA)刺激以表达IL-1 mRNA。与单独使用LPS或PMA相比,二丁酰cAMP、8-溴-cAMP、福斯可林、霍乱毒素、前列腺素E1(PGE1)和前列腺素E2(PGE2)与PMA或LPS协同作用,使细胞系中IL-1α mRNA的积累增加高达50倍,IL-1β mRNA的积累增加10至20倍。单核细胞中IL-1α和IL-1β mRNA积累的这种增加较为适度。这种协同刺激是由于IL-1基因转录速率增强而非IL-1 mRNA稳定性增加所致。尽管IL-1 mRNA积累显著增加,但这些细胞中IL-1蛋白合成仅增加两倍。因此,单核细胞和骨髓单核细胞系中的IL-1合成受到严格的翻译控制。