ADRENOCORTICOTROPIN INCREASES INTERLEUKIN-6 RELEASE FROM RAT ADRENAL ZONA GLOMERULOSA CELLS
ADRENOCORTICOTROPIN INCREASES INTERLEUKIN-6 RELEASE FROM RAT ADRENAL ZONA GLOMERULOSA CELLS
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DOI：
10.1210/en.130.3.1245
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发表时间：
1992-03-01
期刊：
影响因子：
4.8
通讯作者：
MACLEOD, RM
中科院分区：
文献类型：
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作者：
JUDD, AM;MACLEOD, RM
白细胞介素6(IL-6)由肾上腺肾小球带细胞产生，其释放受多种促分泌剂的刺激，包括IL-1-α、IL-1-β和血管紧张素II。本文报道ACTH(0.1-100 nM)以浓度依赖的方式促进原代培养的大鼠肾上腺细胞释放IL-6。这种增加伴随着细胞提取液和孵育液中cAMP含量的增加。用灌流系统研究了肾上腺细胞释放IL-6的动力学；大约需要50分钟才能使IL-1-α、IL-1-β和ACTH对IL-6释放的影响变得明显。停用促分泌剂后，IL-6释放在90-120分钟内恢复到基础水平。在一些实验中，将肾上腺球状带与束/网状带分离，以确定促分泌剂刺激的IL-6释放的来源。PGE2和Forsklin可促进两种细胞的IL-6释放，但肾小球带细胞的最大释放量是束/网状带细胞的10倍以上。ACTH(0.1-100 nM)以浓度依赖的方式增加两种细胞的细胞内cAMP水平，但只增加肾小球带细胞释放IL-6。地塞米松是几个组织产生IL-6的抑制剂，对肾上腺基础或刺激产生的IL-6都没有影响。由于IL-1-β主要由免疫系统的组织产生，而ACTH是一种经典的内分泌激素，因此我们研究了这些蛋白相互作用对肾上腺释放IL-6的影响。IL-1-β和ACTH对IL-6释放的刺激分别大于各自作用的总和，但IL-1-β并不增强ACTH对cAMP水平的影响。同样，IL-1-β可增强Forsklin和(Bu)2cAMP刺激的IL-6的释放。因此，肾上腺可能是免疫和内分泌系统的重要交汇点，由于IL-6的释放受IL-1-α、IL-1-β、ACTH和血管紧张素II的调节，并且这种细胞因子刺激皮质酮的释放，因此IL-6可能在整合这些系统产生的信号中发挥重要的旁分泌作用。
Interleukin-6 (IL-6) is produced by adrenal zona glomerulosa cells; its release is stimulated by several secretagogues, including IL-1-alpha, IL-1-beta, and angiotensin II. The present study reports that ACTH (0.1-100 nM) increased the release of IL-6 from primary cultures of rat adrenal cells in a concentration-dependent manner. This increase was accompanied by an increase in cAMP content in cell extracts and in the incubation medium. The dynamics of IL-6 release from the adrenal cells also were investigated using a perifusion system; approximately 50 min were required for the effects of IL-1-alpha, IL-1-beta, and ACTH on IL-6 release to become apparent. Following withdrawal of the secretagogues, IL-6 release returned to basal levels within 90-120 min. In some experiments, the adrenal zona glomerulosa was separated from the zona fasciculata/reticularis to determine the origin of secretagogue-stimulated IL-6 release. PGE2 and forskolin increased IL-6 release from both cell types, but maximal release from zona glomerulosa cells was more than 10-fold greater than that from zona fasciculata/reticularis cells. ACTH (0.1-100 nM) increased intracellular cAMP levels in cells from both cell types in a concentration-dependent manner, but increased IL-6 release only from zona glomerulosa cells. Dexamethasone, an inhibitor of IL-6 production in several tissues, had no effect on either basal or stimulated IL-6 production in the adrenal. Because IL-1-beta is produced primarily by tissues of the immune system, whereas ACTH is a classical endocrine hormone, we investigated the effect of interaction of these proteins on IL-6 release from the adrenal. Together, IL-1-beta and ACTH stimulation of IL-6 release was greater than the sum of the effects of each substance separately; however, IL-1-beta did not potentiate the effect of ACTH on cAMP levels. Similarly, IL-1-beta potentiated IL-6 release stimulated by forskolin and (Bu)2cAMP. Thus, the adrenal may be an important convergence point between the immune and endocrine systems, and because IL-6 release is regulated by IL-1-alpha, IL-1-beta, ACTH, and angiotensin II, and this cytokine stimulates corticosterone release, IL-6 may play an important paracrine role in integrating the signals derived from these systems.