Ribosome-Inactivating Protein α-Momorcharin Derived from Edible Plant Momordica charantia Induces Inflammatory Responses by Activating the NF-kappaB and JNK Pathways
Ribosome-Inactivating Protein α-Momorcharin Derived from Edible Plant Momordica charantia Induces Inflammatory Responses by Activating the NF-kappaB and JNK Pathways
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DOI：
10.3390/toxins11120694
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发表时间：
2019-12-01
期刊：
影响因子：
4.2
通讯作者：
Yu, Zhi-Ling
中科院分区：
文献类型：
--
作者：
Chen, Ying-Jie;Zhu, Jia-Qian;Yu, Zhi-Ling
α -momorcharin （α - mmc）是核糖体失活蛋白（RIP）家族的一员，已在苦瓜种子中发现。α - mmc具有多种药理活性；然而，其炎症特性尚未得到很好的研究。在这里，我们的目的是确定重组α - mmc诱导的炎症反应，并通过细胞培养和动物模型确定其潜在机制。重组α - mmc在Rosetta (TM)(DE3)pLysS中生成，并通过硝基三乙酸（NTA）层析纯化。40 μ g/mL重组α - mmc对THP-1单核细胞具有亚致死的细胞毒作用。转录谱分析显示，重组α - mmc处理后，THP-1细胞中编码细胞因子和其他促炎蛋白的多种基因上调，包括MCP-1、IL-8、IL-1 β和tnf - α。重组α - mmc被证明可以激活IKK/NF-kappa B和JNK通路，α - mmc诱导的炎症基因表达可以被IKK β和JNK抑制剂阻断。此外，小鼠炎症模型进一步证明了α - mmc在体内诱导炎症反应。我们得出结论，α - mmc通过激活IKK/NF-kappa B和JNK途径刺激人类单核细胞的炎症反应，这提高了食用含有α - mmc的食物可能导致炎症相关疾病的可能性。
Alpha-momorcharin (alpha-MMC), a member of the ribosome-inactivating protein (RIP) family, has been found in the seeds of Momordica charantia (bitter melon). alpha-MMC contributes a number of pharmacological activities; however, its inflammatory properties have not been well studied. Here, we aim to determine the inflammatory responses induced by recombinant alpha-MMC and identify the underlying mechanisms using cell culture and animal models. Recombinant alpha-MMC was generated in Rosetta (TM)(DE3)pLysS and purified by the way of nitrilotriacetic acid (NTA) chromatography. Treatment of recombinant alpha-MMC at 40 mu g/mL exerted sub-lethal cytotoxic effect on THP-1 monocytic cells. Transcriptional profiling revealed that various genes coding for cytokines and other proinflammatory proteins were upregulated upon recombinant alpha-MMC treatment in THP-1 cells, including MCP-1, IL-8, IL-1 beta, and TNF-alpha. Recombinant alpha-MMC was shown to activate IKK/NF-kappa B and JNK pathways and the alpha-MMC-induced inflammatory gene expression could be blocked by IKK beta and JNK inhibitors. Furthermore, murine inflammatory models further demonstrated that alpha-MMC induced inflammatory responses in vivo. We conclude that alpha-MMC stimulates inflammatory responses in human monocytes by activating of IKK/NF-kappa B and JNK pathways, raising the possibility that consumption of alpha-MMC-containing food may lead to inflammatory-related diseases.