Department of Internal Medicine, Chonbuk National University Medical School, San 2-20 Geumam-dong, Deokjin-gu, Jeonju, Jeonbuk, South Korea.
Am J Respir Crit Care Med. 2011 Apr 15;183(8):1015-24. doi: 10.1164/rccm.200906-0902OC. Epub 2010 Apr 22.
Cellular redox homeostasis altered by excessive production of reactive oxygen species (ROS) and weakening of the antioxidant defense leads to oxidative stress. Oxidative stress is characterized as a decrease in glutathione/glutathione disulfide (GSH/GSSG) and the triggering of a number of the redox-sensitive signaling cascades. Recent studies have demonstrated that ROS play an important role in the pathogenesis of airway inflammation and hyperresponsiveness.
Here we characterized for the first time the protective properties of a new hydrophobic thiol compound, N-acetyl cysteine proline cysteine amide (CB3), in allergic airway diseases.
We used ovalbumin (OVA)-inhaled mice to evaluate the role of CB3 as an antiinflammatory reagent and to determine its molecular signaling activity in allergic airways.
The administration of CB3 (1-50 mg/kg) to OVA-inhaled mice restored the decreased GSH levels, enhanced IL-10 expression, and significantly reduced the increase of Th2 cytokines and OVA-specific IgE. CB3 decreased the number of inflammatory cells and airway hyperresponsiveness in the lungs. We also found that the administration of CB3 dramatically decreased the nuclear translocation of the nuclear factor-κB (NF-κB) and the phosphorylation of p38 mitogen-activated protein kinases (MAPKs) in lungs after OVA inhalation. In addition, allergen-induced airway inflammation and hyperresponsiveness were substantially reduced by the administration of inhibitors of NF-κB and p38 MAPK, BAY 11-7085, and SB 239063, respectively.
These results suggest that CB3 attenuates allergic airway disease by up-regulation of GSH levels as well as inhibition of NF-κB and p38 MAPK activity.
活性氧（ROS）产生过多和抗氧化防御减弱导致细胞氧化还原稳态改变，从而引发氧化应激。氧化应激的特征是谷胱甘肽/谷胱甘肽二硫化物（GSH/GSSG）减少，并触发许多氧化还原敏感的信号级联反应。最近的研究表明，ROS 在气道炎症和高反应性的发病机制中起重要作用。
本研究首次描述了一种新型疏水性硫醇化合物 N-乙酰半胱氨酸脯氨酸半胱氨酸酰胺（CB3）在过敏性气道疾病中的保护特性。
我们使用卵清蛋白（OVA）吸入小鼠来评估 CB3 作为抗炎试剂的作用，并确定其在过敏性气道中的分子信号活性。
给予 OVA 吸入小鼠 CB3（1-50mg/kg）可恢复降低的 GSH 水平，增强 IL-10 表达，并显著降低 Th2 细胞因子和 OVA 特异性 IgE 的增加。CB3 减少了肺部炎症细胞和气道高反应性。我们还发现，给予 CB3 可显著减少 OVA 吸入后肺部核因子-κB（NF-κB）的核易位和丝裂原活化蛋白激酶（MAPKs）的磷酸化。此外，NF-κB 和 p38 MAPK 的抑制剂 BAY 11-7085 和 SB 239063 分别给药可显著减轻过敏原诱导的气道炎症和高反应性。
这些结果表明，CB3 通过上调 GSH 水平以及抑制 NF-κB 和 p38 MAPK 活性来减轻过敏性气道疾病。
