Gessani S, McCandless S, Baglioni C
Department of Biological Sciences, State University of New York, Albany 12222.
J Biol Chem. 1988 Jun 5;263(16):7454-7.
Human fibroblasts were induced to secrete interferon (IFN) by treatment with the double-stranded RNA poly(inosinic).poly(cytidylic) acid or by infection with Newcastle disease virus. Treatment with 0.1-1 microM dexamethasone reduced the amount of IFN secreted by approximately 40-70%, respectively. A similar decrease in secretion of human IFN-beta was detected in dexamethasone-treated murine C127 cells that carry an IFN expression vector. These cells transcribe constitutively human IFN-beta under the control of a viral thymidine kinase promotor. Secretion of murine IFN induced by double-stranded RNA was also reduced in dexamethasone-treated C127 cells. The amount of IFN-beta mRNA present in fibroblasts and C127 cells was measured by hybridization to complementary RNA. Treatment with dexamethasone markedly reduced the level of IFN-beta mRNA present in both cells. The time course of this decrease was measured in C127 cells; 50 and 80% loss of IFN mRNA was observed after approximately 7.5 and 12 h, respectively. Murine IFN mRNA was also decreased in dexamethasone-treated C127 cells induced with double-stranded RNA. However, the rate of transcription of human IFN mRNA measured by run-on assays in isolated nuclei of dexamethasone-treated C127 cells was found to be comparable to that of control untreated cells. The finding that dexamethasone reduces the level of IFN mRNA transcribed under the control of both its own promotor and an unrelated promotor, together with the observation that dexamethasone does not apparently alter the rate of transcription of this mRNA, suggest that glucocorticoids may regulate IFN production by decreasing the level of its mRNA.
用双链RNA聚肌苷酸-聚胞苷酸处理或感染新城疫病毒可诱导人成纤维细胞分泌干扰素（IFN）。用0.1 - 1微摩尔/升地塞米松处理分别使分泌的IFN量减少约40 - 70%。在携带IFN表达载体的经地塞米松处理的鼠C127细胞中，也检测到人类IFN-β分泌有类似减少。这些细胞在病毒胸苷激酶启动子的控制下持续转录人类IFN-β。在经地塞米松处理的C127细胞中，双链RNA诱导的鼠IFN分泌也减少。通过与互补RNA杂交来测量成纤维细胞和C127细胞中存在的IFN-β mRNA的量。用地塞米松处理显著降低了两种细胞中存在的IFN-β mRNA的水平。在C127细胞中测量了这种减少的时间进程；分别在约7.5小时和12小时后观察到IFN mRNA损失了50%和80%。在经双链RNA诱导的经地塞米松处理的C127细胞中，鼠IFN mRNA也减少。然而，通过在经地塞米松处理的C127细胞的分离细胞核中进行连续分析测量的人类IFN mRNA转录速率，发现与未处理的对照细胞相当。地塞米松降低在其自身启动子和无关启动子控制下转录的IFN mRNA水平这一发现，以及地塞米松显然不改变该mRNA转录速率的观察结果，表明糖皮质激素可能通过降低其mRNA水平来调节IFN的产生。
