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-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.
Original language | English |
---|---|
Article number | 694 |
Number of pages | 17 |
Journal | Toxins |
Volume | 11 |
Issue number | 12 |
DOIs | |
Publication status | Published - 26 Nov 2019 |
Scopus Subject Areas
- Toxicology
- Health, Toxicology and Mutagenesis
User-Defined Keywords
- Alpha-momorcharin
- Inflammation
- JNK
- NF-kappaB
- Ribosome inactivating protein