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

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.