Cytokine regulation of tryptophan metabolism in the hypothalamic-pituitary-adrenal (HPA) axis: implications for protective and toxic consequences in neuroendocrine regulation.
Cytokine regulation of tryptophan metabolism in the hypothalamic-pituitary-adrenal (HPA) axis: implications for protective and toxic consequences in neuroendocrine regulation.
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下丘脑-垂体-肾上腺（HPA）轴色氨酸代谢的细胞因子调节：对神经内分泌调节的保护性和毒性后果的影响。
DOI：
10.1007/s10571-005-4007-1
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发表时间：
2005
影响因子：
4
通讯作者：
Hughes,ThomasK
中科院分区：
文献类型：
--
作者：
Tu,Huolin;Rady,PeterL;Juelich,Terry;Smith,EricM;Tyring,StephenK;Hughes,ThomasK
1.目的：在大多数组织中，吲哚胺2,3-双加氧酶（IDO）催化色氨酸是犬尿氨酸途径的第一个限速步骤。犬尿氨酸途径产生神经毒性代谢物，例如 3-羟基犬尿氨酸和喹啉酸。 IDO 由细胞因子干扰素-γ (IFN-γ) 诱导，并被提议介导感染性或其他炎症性疾病患者的疾病行为。为了更好地了解细胞因子诱发的疾病行为的神经内分泌成分，我们确定了促炎细胞因子 IFN-γ 和抗炎细胞因子 IL-10 对源自下丘脑-垂体-肾上腺轴 (HPA) 的细胞中 IDO 表达的影响：GT1-7 下丘脑、 AtT-20 垂体细胞和 Y-1 肾上腺细胞。 2.方法：进行逆转录聚合酶链反应（RT-PCR）检查 IFN-γ 和 IL-10 处理的细胞（如 GT1-7、AtT-20 和 Y-1 细胞）的 IDO 表达。 3.结果：我们发现 IFN-γ 处理 GT1-7 和 AtT-20 细胞 4 小时后诱导 IDO 表达。 IL-10 还能够抑制这些细胞中 IFN-γ 诱导的 IDO 表达。在Y-1肾上腺细胞中，IFN-γ处理对IDO表达没有影响。4.结论：我们的结果表明，IFN-γ和IL-10等细胞因子能够调节下丘脑和垂体来源的细胞中IDO的表达。 IL-10 抑制 IFN-γ 诱导的 IDO 表达的能力表明 IL-10 在 HPA 轴中具有假定的神经保护作用。它可以在两个层面发挥作用，系统性地通过抑制与疾病行为相关的 Th1 细胞因子合成，更集中地通过抑制犬尿氨酸途径。
1.Aim: Indoleamine 2,3-dioxygenase (IDO) catalyzation of tryptophan is the first rate-limiting step of the kynurenine pathway in the majority of tissues. The kynurenine pathway produces neurotoxic metabolites such as 3-hydroxykinurenine and quinolinic acid. IDO is inducible by the cytokine interferon-γ (IFN-γ) and has been proposed to mediate the sickness behavior of patients with infectious or other inflammatory diseases.To better understand the neuroendocrine component of cytokine induced sickness behavior we determined the effects of the pro-inflammatory cytokine IFN-γ and the anti-inflammatory cytokine IL-10 on IDO expression in cells derived from the hypothalamic-pituitary-adrenal axis (HPA): GT1-7 hypothalamic, AtT-20 pituitary, and Y-1 adrenal cells.2.Methods: Reverse transcriptase polymerase chain reaction (RT-PCR) was performed to check the IDO expression from IFN-γ and IL-10 treated cells such as GT1-7, AtT-20 and Y-1 cells.3.Results: We found that IFN-γ induces IDO expression after 4 h treatment in GT1-7 and AtT-20 cells. IL-10 was also able to suppress IFN-γ induced IDO expression in these cells. In Y-1 adrenal cells, IFN-γ treatment had no effect on IDO expression.4.Conclusions: Our results indicate that cytokines such as IFN-γ and IL-10 are able to regulate IDO expression in cells of hypothalamic and pituitary origin. The ability of IL-10 to suppress IFN-γ induced IDO expression implies that IL-10 has a putative neuroprotective role in the HPA axis. It can act at two levels, systemically by inhibiting sickness behavior—related Th1 cytokine synthesis and more centrally by inhibiting the kynurenine pathway.