Department of Biology, University of Naples "Federico II", 80126 Naples, Italy.
Department of Translational Medical Science-Pediatric Section, University of Naples "Federico II", 80131 Naples, Italy.
Nutrients. 2018 Jun 8;10(6):744. doi: 10.3390/nu10060744.
Evidence suggests a relevant role for liver and mitochondrial dysfunction in allergic disease. However, the role of hepatic mitochondrial function in food allergy is largely unknown. We aimed to investigate hepatic mitochondrial dysfunction in a murine model of peanut allergy.
Three-week-old C3H/HeOuJ mice were sensitized by the oral route with peanut-extract (PNT). We investigated: 1. the occurrence of effective sensitization to PNT by analysing acute allergic skin response, anaphylactic symptoms score, body temperature, serum mucosal mast cell protease-1 (mMCP-1) and anti-PNT immunoglobulin E (IgE) levels; 2. hepatic involvement by analysing interleukin (IL)-4, IL-5, IL-13, IL-10 and IFN-γ mRNA expression; 3. hepatic mitochondrial oxidation rates and efficiency by polarography, and hydrogen peroxide (H₂O₂) yield, aconitase and superoxide dysmutase activities by spectrophotometry.
Sensitization to PNT was demonstrated by acute allergic skin response, anaphylactic symptoms score, body temperature decrease, serum mMCP-1 and anti-peanut IgE levels. Liver involvement was demonstrated by a significant increase of hepatic Th2 cytokines (IL-4, IL-5 and IL-13) mRNA expression. Mitochondrial dysfunction was demonstrated by lower state 3 respiration rate in the presence of succinate, decreased fatty acid oxidation in the presence of palmitoyl-carnitine, increased yield of ROS proven by the inactivation of aconitase enzyme and higher H₂O₂ mitochondrial release.
We provide evidence of hepatic mitochondrial dysfunction in a murine model of peanut allergy. These data could open the way to the identification of new mitochondrial targets for innovative preventive and therapeutic strategies against food allergy.
有证据表明，肝脏和线粒体功能障碍与过敏疾病有关。然而，食物过敏中肝线粒体功能的作用在很大程度上尚不清楚。我们旨在研究花生过敏的小鼠模型中的肝线粒体功能障碍。
3 周龄的 C3H/HeOuJ 小鼠通过口服途径用花生提取物（PNT）致敏。我们调查了：1. 通过分析急性过敏皮肤反应、过敏症状评分、体温、血清黏膜肥大细胞蛋白酶-1（mMCP-1）和抗 PNT 免疫球蛋白 E（IgE）水平，确定对 PNT 发生有效致敏的情况；2. 通过分析白细胞介素（IL）-4、IL-5、IL-13、IL-10 和 IFN-γmRNA 表达，分析肝脏受累情况；3. 通过极谱法分析肝线粒体氧化率和效率，通过分光光度法分析氢过氧化物（H₂O₂）产量、顺乌头酸酶和超氧化物歧化酶活性。
通过急性过敏皮肤反应、过敏症状评分、体温下降、血清 mMCP-1 和抗花生 IgE 水平证实了 PNT 的致敏作用。肝脏受累通过肝 Th2 细胞因子（IL-4、IL-5 和 IL-13）mRNA 表达的显著增加得到证实。线粒体功能障碍通过在琥珀酸存在下降低状态 3 呼吸率、在棕榈酰肉碱存在下降低脂肪酸氧化、通过失活乌头酸酶证实 ROS 产量增加以及更高的 H₂O₂线粒体释放来证明。
我们提供了花生过敏小鼠模型中肝线粒体功能障碍的证据。这些数据可能为识别针对食物过敏的创新预防和治疗策略的新线粒体靶点开辟道路。
