Autism spectrum disorder (ASD) is a very complex neurodevelopmental disorder characterized by deficits in social and communication skills. Innate immune cells like monocytes are believed to play a cardinal role in neuroimmune inflammation and nitrative stress. On the other hand, Nrf2, a basic leucine zipper transcription factor plays a significant role in protecting the immune cells against inflammation and oxidants. However, its role in monocytes of ASD children and typically developing control (TDC) children has not been elucidated in relation with inflammation and nitrative stress. Therefore, this study was undertaken to evaluate Nrf2 expression/activity along with parameters of inflammation (NFkB, IL-6, IL-1β) and nitrative stress (iNOS, nitrotyrosine) in monocytes of ASD/TDC children. Further, sulforaphane (SFN) was utilized as an Nrf2 activator to assess its effect on above said inflammatory and nitrative stress parameters. Our study shows that monocytes of ASD subjects have decreased Nrf2 expression/activity along with increased inflammation and nitrative stress. Further, monocytes from ASD have deficiency in induction of Nrf2 activity upon stimulation with LPS. However, activation of Nrf2 in vitro by SFN reverses LPS-induced effects on inflammation in monocytes by reduction in NFkB signaling. Further, treatment with SFN also reverses LPS-induced effects on nitrative stress (iNOS, nitrotyrosine) in monocytes of ASD subjects. This study propounds the idea that SFN protects against nitrative stress and inflammation by downregulating oxidative stress and inflammation through blockade of NFkB signaling in autistic children. This may be the reason behind reported ameliorative effects of SFN in ASD subjects.

中文翻译：

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Nrf2的差异调节与自闭症儿童单核细胞炎症和硝化应激升高有关

自闭症谱系障碍 (ASD) 是一种非常复杂的神经发育障碍，其特征是社交和沟通技巧的缺陷。单核细胞等先天免疫细胞被认为在神经免疫炎症和硝化应激中发挥着重要作用。另一方面，Nrf2，一种碱性亮氨酸拉链转录因子，在保护免疫细胞免受炎症和氧化剂侵害方面发挥着重要作用。然而，其在 ASD 儿童和典型发育控制 (TDC) 儿童的单核细胞中的作用尚未阐明与炎症和硝化应激的关系。因此，本研究旨在评估 ASD/TDC 儿童单核细胞中 Nrf2 的表达/活性以及炎症参数（NFkB、IL-6、IL-1β）和硝化应激（iNOS、硝基酪氨酸）。更多，萝卜硫素 (SFN) 被用作 Nrf2 激活剂来评估其对上述炎症和硝化应激参数的影响。我们的研究表明，ASD 受试者的单核细胞 Nrf2 表达/活性降低，同时炎症和硝化应激增加。此外，来自 ASD 的单核细胞在用 LPS 刺激后缺乏 Nrf2 活性的诱导。然而，SFN 在体外激活 Nrf2 通过减少 NFkB 信号传导来逆转 LPS 对单核细胞炎症的影响。此外，SFN 治疗还可以逆转 LPS 对 ASD 受试者单核细胞中硝化应激（iNOS、硝基酪氨酸）的影响。这项研究提出了这样的观点，即 SFN 通过阻断自闭症儿童的 NFkB 信号传导来下调氧化应激和炎症，从而防止硝化应激和炎症。