Ribosome-inactivating protein α-momorcharin derived from edible plant momordica charantia induces inflammatory responses by activating the NF-kappaB and JNK pathways

Ying Jie Chen, Jia Qian Zhu, Xiuqiong FU, Tao Su, Ting Li, Hui Guo, Pei Li Zhu, Sally Kin Wah Lee, Hua Yu, Anfernee K W TSE, Zhiling YU*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)

Abstract

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-MMCtreatment 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.

Original languageEnglish
Article number694
JournalToxins
Volume11
Issue number12
DOIs
Publication statusPublished - 26 Nov 2019

Scopus Subject Areas

  • Toxicology
  • Health, Toxicology and Mutagenesis

User-Defined Keywords

  • Alpha-momorcharin
  • Inflammation
  • JNK
  • NF-kappaB
  • Ribosome inactivating protein

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