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Open AccessArticle

Ribosome-Inactivating Protein α-Momorcharin Derived from Edible Plant Momordica charantia Induces Inflammatory Responses by Activating the NF-kappaB and JNK Pathways

1
Center for Cancer and Inflammation Research, School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, Hong Kong, China
2
State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, China
3
Food Science and Technology Program, Beijing Normal University-Hong Kong Baptist University United International College, Zhuhai 519087, China
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Toxins 2019, 11(12), 694; https://doi.org/10.3390/toxins11120694
Received: 2 October 2019 / Revised: 17 November 2019 / Accepted: 25 November 2019 / Published: 26 November 2019
(This article belongs to the Section Plant Toxins)
Alpha-momorcharin (α-MMC), a member of the ribosome-inactivating protein (RIP) family, has been found in the seeds of Momordica charantia (bitter melon). α-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 α-MMC and identify the underlying mechanisms using cell culture and animal models. Recombinant α-MMC was generated in Rosetta™(DE3)pLysS and purified by the way of nitrilotriacetic acid (NTA) chromatography. Treatment of recombinant α-MMC at 40 μg/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 α-MMC treatment in THP-1 cells, including MCP-1, IL-8, IL-1β, and TNF-α. Recombinant α-MMC was shown to activate IKK/NF-κB and JNK pathways and the α-MMC-induced inflammatory gene expression could be blocked by IKKβ and JNK inhibitors. Furthermore, murine inflammatory models further demonstrated that α-MMC induced inflammatory responses in vivo. We conclude that α-MMC stimulates inflammatory responses in human monocytes by activating of IKK/NF-κB and JNK pathways, raising the possibility that consumption of α-MMC-containing food may lead to inflammatory-related diseases.
Keywords: alpha-momorcharin; inflammation; JNK; NF-kappaB; ribosome inactivating protein alpha-momorcharin; inflammation; JNK; NF-kappaB; ribosome inactivating protein
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Chen, Y.-J.; Zhu, J.-Q.; Fu, X.-Q.; Su, T.; Li, T.; Guo, H.; Zhu, P.-L.; Lee, S.-W.; Yu, H.; Tse, A.-W.; Yu, Z.-L. Ribosome-Inactivating Protein α-Momorcharin Derived from Edible Plant Momordica charantia Induces Inflammatory Responses by Activating the NF-kappaB and JNK Pathways. Toxins 2019, 11, 694.

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