Graduate Institute of Clinical Medical Sciences, Chang Gung University College of Medicine, Kaohsiung, Taiwan.
Liver Transplantation Center and Department of Surgery, Division of Transplant Immunology, Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
Int Forum Allergy Rhinol. 2017 Nov;7(11):1095-1103. doi: 10.1002/alr.22008. Epub 2017 Sep 1.
Oxidative stress is involved in various diseases, including allergies. Several studies have pointed to the preventive and therapeutic potential of antioxidants in allergic disorders. However, little is known about the immunomodulatory effects of antioxidants in type I hypersensitivity. In this study we aimed to explore the impact of a water-soluble antioxidant and α-lipoic acid derivative, sodium zinc histidine dithiooctanamide (DHL-HisZn), on mast-cell- and T-cell-mediated allergic and immune responses both in vitro and in vivo.
The therapeutic impact of DHL-HisZn on mast-cell-mediated type I hypersensitivity was evaluated by a mast-cell degranulation assay using bone marrow-derived mast cells and by a mouse model of ovalbumin (OVA)-induced allergic rhinitis. The effect of DHL-HisZn on the proportion of regulatory T cells (Tregs) was evaluated using flow cytometry.
During the course of OVA-induced allergic rhinitis in mice, serum nitrate was elevated, suggesting the involvement of oxidative stress in allergic responses. DHL-HisZn not only suppressed mast-cell degranulation but also ameliorated OVA-induced nasal hypersensitivity, with significant suppression of serum nitrate. DHL-HisZn treatment significantly suppressed OVA-specific immunoglobulin E (IgE) but enhanced OVA-specific IgG2a in OVA-sensitized and nasal-challenged mice. Furthermore, DHL-HisZn treatment suppressed interleukin-17 production in OVA-stimulated splenocytes. Finally, we demonstrated the induction of Tregs by DHL-HisZn in concanavalin A blasts.
These findings suggest that DHL-HisZn may regulate mast-cell-, T-helper 2 (Th2)-, and Th17-mediated allergic and immune responses by induction of Tregs.
氧化应激与包括过敏在内的各种疾病有关。多项研究指出，抗氧化剂在过敏疾病中具有预防和治疗潜力。然而，对于抗氧化剂在 I 型超敏反应中的免疫调节作用知之甚少。在这项研究中，我们旨在探索一种水溶性抗氧化剂和α-硫辛酸衍生物，即组氨酸锌二硫辛酰胺（DHL-HisZn），对肥大细胞和 T 细胞介导的过敏和免疫反应的体内和体外的影响。
通过骨髓来源的肥大细胞的肥大细胞脱颗粒测定和卵清蛋白（OVA）诱导的过敏性鼻炎的小鼠模型，评估 DHL-HisZn 对肥大细胞介导的 I 型超敏反应的治疗作用。通过流式细胞术评估 DHL-HisZn 对调节性 T 细胞（Tregs）比例的影响。
在小鼠 OVA 诱导的过敏性鼻炎过程中，血清硝酸盐升高，表明氧化应激参与了过敏反应。DHL-HisZn 不仅抑制肥大细胞脱颗粒，还改善了 OVA 诱导的鼻过敏，显著抑制了血清硝酸盐。DHL-HisZn 治疗显著抑制了 OVA 致敏和鼻挑战小鼠的 OVA 特异性免疫球蛋白 E（IgE），但增强了 OVA 特异性 IgG2a。此外，DHL-HisZn 治疗抑制了 OVA 刺激的脾细胞中白细胞介素-17 的产生。最后，我们证明了 DHL-HisZn 在刀豆蛋白 A 原代细胞中诱导 Tregs。
这些发现表明，DHL-HisZn 可能通过诱导 Tregs 来调节肥大细胞、辅助性 T 细胞 2（Th2）和 Th17 介导的过敏和免疫反应。
