de Bie J, Lim C K, Guillemin G J
Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Macquarie University, Sydney, NSW, Australia.
Int J Tryptophan Res. 2016 Dec 7;9:89-93. doi: 10.4137/IJTR.S40332. eCollection 2016.
We have previously demonstrated that the kynurenine pathway (KP), the major biochemical pathway for tryptophan metabolism, is dysregulated in many inflammatory disorders that are often associated with sexual dimorphisms. We aimed to identify a potential functional interaction between the KP and gonadal hormones. We have treated primary human macrophages with progesterone in the presence and absence of inflammatory cytokine interferon-gamma (interferon-γ) that is known to be a potent inducer of regulating the KP enzyme. We found that progesterone attenuates interferon-γ-induced KP activity, decreases the levels of the excitotoxin quinolinic acid, and increases the neuroprotective kynurenic acid levels. We also showed that progesterone was able to reduce the inflammatory marker neopterin. These results may shed light on the gender disparity in response to inflammation.
我们之前已经证明，犬尿氨酸途径（KP）作为色氨酸代谢的主要生化途径，在许多通常与性别二态性相关的炎症性疾病中失调。我们旨在确定KP与性腺激素之间潜在的功能相互作用。我们用孕酮处理原代人巨噬细胞，分别在存在和不存在炎性细胞因子干扰素-γ（干扰素-γ）的情况下进行处理，已知干扰素-γ是调节KP酶的有效诱导剂。我们发现孕酮减弱了干扰素-γ诱导的KP活性，降低了兴奋性毒素喹啉酸的水平，并提高了具有神经保护作用的犬尿喹啉酸水平。我们还表明，孕酮能够降低炎症标志物新蝶呤。这些结果可能有助于揭示炎症反应中的性别差异。
