Interleukins 1α and 1β as regulators of steroidogenesis in human NCI-H295R adrenocortical cells
Interleukins 1α and 1β as regulators of steroidogenesis in human NCI-H295R adrenocortical cells
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DOI：
10.1016/j.steroids.2011.04.018
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发表时间：
2011-09-01
期刊：
影响因子：
2.7
通讯作者：
Voutilainen, Raimo
中科院分区：
文献类型：
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作者：
Tkachenko, Irina V.;Jaaskelainen, Tiina;Voutilainen, Raimo
炎性细胞因子白细胞介素-1（IL-1）和肿瘤坏死因子-α（TNF-α）在几个水平上调节下丘脑-垂体-肾上腺（HPA）轴的活性。虽然下丘脑CRH分泌可能是这些细胞因子激活HPA轴的主要机制，但在全身性炎症模型中，肾上腺内IL-1表达增加，并且IL-1可能增加肾上腺糖皮质激素的产生。我们的目的是研究IL-1 α和IL-1 β对肾上腺类固醇生成的直接影响，以及使用NCI-H295 R细胞系作为模型的人肾上腺皮质细胞中三个关键类固醇生成基因的表达。在细胞系中可检测到编码IL-1、TNF-α和白血病抑制因子（LIF）受体的mRNA（Affyssin微阵列分析）。IL-1 α和IL-1 β均增加皮质醇、雄烯二酮、脱氢表雄酮和硫酸脱氢表雄酮的产生，以及类固醇生成急性调节蛋白（星星）、17 α-羟化酶/17，20-裂解酶（CYP 17 A1）和3 β-羟基类固醇脱氢酶2（HSD 3B 2）mRNA在这些细胞中的积累（均P < 0.05）。两种IL均增加TNF-α和LIF诱导的星星和CYP 17 A1 mRNA的积累，以及TNF-α诱导的皮质醇产生（P均< 0.05）。两种IL均能显著增加细胞凋亡指数（P < 0.05），并能被其特异性抗体中和。IL诱导的星星、HSD 3B 2和CYP 17 A1蛋白水平的变化不如相应mRNA水平的变化明显。总之，急性或慢性炎症状态下肾上腺水平的炎性细胞因子的联合作用可以显著刺激糖皮质激素的产生，从而解释了有时在脓毒症和慢性炎症状态下观察到的皮质醇和ACTH浓度之间的差异。(C)2011 Elsevier Inc. All rights reserved.
Inflammatory cytokines interleukin-1 (IL-1) and tumor necrosis factor-alpha (TNF-alpha) regulate the activity of the hypothalamo-pituitary-adrenal (HPA) axis at several levels. Although hypothalamic CRH secretion may be the primary mechanism by which these cytokines activate the HPA axis, IL-1 expression is increased within the adrenal glands in models for systemic inflammation, and IL-1 may augment adrenal glucocorticoid production. Our aim was to investigate the direct effects of IL-1 alpha and IL-1 beta on adrenal steroidogenesis and expression of three key steroidogenic genes in human adrenocortical cells using the NCI-H295R cell line as a model. mRNAs encoding receptors for IL-1, TNF-alpha, and leukemia inhibitory factor (LIF) were detectable in the cell line (Affymetrix microarray analysis). Both IL-1 alpha and IL-1 beta increased cortisol, androstenedione, dehydroepiandrosterone and dehydroepiandrosterone sulfate production, and the accumulation of mRNAs for steroidogenic acute regulatory protein (STAR), 17 alpha-hydroxylase/17,20-lyase (CYP17A1) and 3 beta-hydroxysteroid dehydrogenase 2 (HSD3B2) in these cells (P < 0.05 for all). Both ILs augmented TNF-alpha- and LIF-induced STAR and CYP17A1 mRNA accumulation, and TNF-alpha-induced cortisol production (P < 0.05 for all). Both ILs also increased the apoptotic index of the cells (P < 0.05), which was efficiently neutralized by their specific antibodies. The IL-induced changes in the STAR, HSD3B2, and CYP17A1 protein levels were not as evident as those in the respective mRNA levels. In conclusion, the combined effect of inflammatory cytokines at the adrenal level in acute or chronic inflammatory states could significantly stimulate glucocorticoid production, and thus explain the observed discrepancy between the cortisol and ACTH concentrations sometimes seen in sepsis and chronic inflammatory states. (C) 2011 Elsevier Inc. All rights reserved.