Introduction: IL-1β, a cytokine from the innate immune response, is well known for its proinflammatory effects and stimulating activity on the hypothalamus-pituitary-adrenal axis, leading to the pituitary synthesis of adrenocorticotropic hormone followed by cortisol (and dehydroepiandrosterone – DHEA) release by the adrenal gland. While IL-1β modulates the adrenal steroidogenesis at the central level, it is unclear whether it also exerts an effect on the adrenal gland. Method: We studied the effect of IL-1β on adrenal steroid production and steroidogenic enzyme RNA expression in the human cell line NCI-H295R. We also explored eventual changes in the microRNA (miRNA) profile from IL-1β-treated NCI-H295R cells. Results: Transcripts encoding IL-1β receptors 1 and 2 were noticeable in the cell line, with cortisol and DHEA production showing a subtle increase after cytokine treatment. Transcripts from key enzymes in the steroidogenic pathway were analyzed, with no noticeable changes on them. The miRNA profile was modified by IL-1β treatment to an extent which bears some relationship with the regulatory mechanisms underlying adrenal steroid production. Since orphan nuclear receptors NR4As have emerged as potential key factors for coordinating inflammatory and metabolic responses, cell expression studies were also carried out to show an NR4As transcript augmentation following IL-1β treatment. Discussion/Conclusions: The subtle increase in adrenal steroid production in response to IL-1β stimulation without any modification in the transcription of the steroidogenic enzymes analyzed suggests an additional inflammatory/anti-inflammatory loop, wherein NR4As receptors may participate. Besides its physiological role, this process might be implied in pathological states accompanied by an unbalanced immune-endocrine relationship.
Neuroimmunomodulation

中文翻译：

---

肾上腺类固醇生成的局部调节：IL-1β 对人细胞系 NCI-H295R 类固醇产生的微妙体外影响以及微小 RNA 谱和孤儿核受体 NR4As 的变化

简介： IL-1β 是一种来自先天免疫反应的细胞因子，以其促炎作用和对下丘脑-垂体-肾上腺轴的刺激活性而闻名，导致垂体合成促肾上腺皮质激素，然后是皮质醇（和脱氢表雄酮 - DHEA）由肾上腺释放。虽然 IL-1β 在中枢水平调节肾上腺类固醇生成，但尚不清楚它是否也对肾上腺产生影响。方法：我们研究了 IL-1β 对人细胞系 NCI-H295R 中肾上腺类固醇生成和类固醇生成酶 RNA 表达的影响。我们还探索了来自 IL-1β 处理的 NCI-H295R 细胞的 microRNA (miRNA) 谱的最终变化。结果：编码 IL-1β 受体 1 和 2 的转录物在细胞系中很明显，在细胞因子处理后皮质醇和 DHEA 的产生显示出微妙的增加。分析了类固醇生成途径中关键酶的转录本，没有明显的变化。miRNA 谱被 IL-1β 处理修饰到一定程度，这与肾上腺类固醇产生的调节机制有关。由于孤儿核受体 NR4As 已成为协调炎症和代谢反应的潜在关键因素，因此还进行了细胞表达研究以显示 IL-1β 治疗后 NR4As 转录增加。讨论/结论：响应 IL-1β 刺激的肾上腺类固醇产生的微妙增加，而分析的类固醇生成酶的转录没有任何改变，这表明存在额外的炎症/抗炎循环，其中 NR4As 受体可能参与其中。除了它的生理作用外，这个过程可能隐含在伴随着不平衡的免疫-内分泌关系的病理状态中。
神经免疫调节