Inhibition of Epithelial TNF-α Receptors by Purified Fruit Bromelain Ameliorates Intestinal Inflammation and Barrier Dysfunction in Colitis.
Inhibition of Epithelial TNF-α Receptors by Purified Fruit Bromelain Ameliorates Intestinal Inflammation and Barrier Dysfunction in Colitis.
复制标题
纯化水果菠萝蛋白酶抑制上皮 TNF-α 受体可改善结肠炎中的肠道炎症和屏障功能障碍
DOI：
10.3389/fimmu.2017.01468
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发表时间：
2017
影响因子：
7.3
通讯作者：
Peng J
中科院分区：
文献类型：
--
作者：
Zhou Z;Wang L;Feng P;Yin L;Wang C;Zhi S;Dong J;Wang J;Lin Y;Chen D;Xiong Y;Peng J
TNF-α受体（TNFR）的激活导致炎症反应，抗TNF治疗已被用于减轻炎症性肠病（IBD）的炎症症状并治愈粘膜溃疡。菠萝蛋白酶是一种复杂的蛋白水解酶的天然混合物，已被证明具有抗炎作用。本研究旨在探讨纯化的菠萝蛋白酶（PFB）诱导的抑制上皮TNFR在大鼠结肠炎模型中的作用。通过结肠内施用2，4，6-三硝基苯磺酸建立结肠炎。采用RT-PCR和Western blotting检测TNFR 1和TNFR 2的表达。通过检测炎症反应和肠上皮屏障功能来评价PFB对结肠炎的影响。我们的研究结果表明，在结肠炎模型中TNFR 1和TNFR 2的表达均显著增加，并且这种增加被PFB显著逆转。结肠炎症状，包括炎症细胞浸润，细胞因子谱，上皮细胞凋亡，上皮紧密连接屏障功能障碍显着改善PFB。与果菠萝蛋白酶和茎菠萝蛋白酶复合物相比，PFB对TNFR 2的抑制作用强于对TNFR 1的抑制作用。这些结果表明，PFB对TNFR 2的选择性抑制作用强于TNFR 1。换句话说，水果菠萝蛋白酶的纯化增加了其对TNFR 2抑制的选择性。结肠炎中上皮TNFR的高表达被PFB显著抵消，PFB诱导的TNFR抑制改善结肠炎症状。这些结果为PFB潜在的IBD治疗提供了新的见解。
Activation of the TNF-α receptor (TNFR) leads to an inflammatory response, and anti-TNF therapy has been administered to reduce inflammation symptoms and heal mucosal ulcers in inflammatory bowel disease (IBD). Bromelain, a complex natural mixture of proteolytic enzymes, has been shown to exert anti-inflammatory effects. This study aimed to investigate the effect of purified fruit bromelain (PFB)-induced inhibition of epithelial TNFR in a rat colitis model. Colitis was established by intracolonic administration of 2, 4, 6-trinitrobenzene sulfonic acid. Expression of TNFR1 and TNFR2 was measured by quantitative RT-PCR and western blotting. The effect of PFB on colitis was evaluated by examining the inflammatory response and intestinal epithelial barrier function. Our results showed that both TNFR1 and TNFR2 expression were significantly increased in a colitis model, and the increase was significantly reversed by PFB. Colitis symptoms, including infiltration of inflammatory cells, cytokine profiles, epithelial cell apoptosis, and epithelial tight junction barrier dysfunction were significantly ameliorated by PFB. Compared with fruit bromelain and stem bromelain complex, the inhibition of TNFR2 induced by PFB was stronger than that exhibited on TNFR1. These results indicate that PFB showed a stronger selective inhibitory effect on TNFR2 than TNFR1. In other words, purification of fruit bromelain increases its selectivity on TNFR2 inhibition. High expression of epithelial TNFRs in colitis was significantly counteracted by PFB, and PFB-induced TNFR inhibition ameliorated colitis symptoms. These results supply novel insights into potential IBD treatment by PFB.