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

ABSTRACT: Alpha-momorcharin (?-MMC), a member of the ribosome-inactivating protein (RIP) family, has been found in the seeds of Momordica charantia (bitter melon). ?-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 ?-MMC and identify the underlying mechanisms using cell culture and animal models. Recombinant ?-MMC was generated in Rosetta™(DE3)pLysS and purified by the way of nitrilotriacetic acid (NTA) chromatography. Treatment of recombinant ?-MMC at 40 ?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 ?-MMC treatment in THP-1 cells, including MCP-1, IL-8, IL-1?, and TNF-?. Recombinant ?-MMC was shown to activate IKK/NF-?B and JNK pathways and the ?-MMC-induced inflammatory gene expression could be blocked by IKK? and JNK inhibitors. Furthermore, murine inflammatory models further demonstrated that ?-MMC induced inflammatory responses in vivo. We conclude that ?-MMC stimulates inflammatory responses in human monocytes by activating of IKK/NF-?B and JNK pathways, raising the possibility that consumption of ?-MMC-containing food may lead to inflammatory-related diseases.

SUBMITTER: Chen YJ 

PROVIDER: S-EPMC6949964 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature