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Published on: January 22, 2019
Tryptanthrin Down-Regulates Oncostatin M by Targeting GM-CSF-Mediated PI3K-AKT-NF-κB Axis
Na-Ra Han1,2, Hi-Joon Park3, Seong-Gyu Ko2,4
1College of Korean Medicine, Kyung Hee University, Seoul 02447, Republic of Korea.
Background:
Oncostatin M (OSM) is involved in several inflammatory responses. Tryptanthrin (TRYP), as a natural alkaloid, is a bioactive compound derived from indigo plants. Objectives/ Methods: The purpose of this study is to investigate the potential inhibitory activity of TRYP on OSM release from neutrophils using neutrophils-like differentiated (d)HL-60 cells and neutrophils from mouse bone marrow.
Results:
The results showed that TRYP reduced the production and mRNA expression levels of OSM in the granulocyte-macrophage colony-stimulating factor (GM-CSF)-stimulated neutrophils-like dHL-60 cells. In addition, TRYP decreased the OSM production levels in the GM-CSF-stimulated neutrophils from mouse bone marrow. TRYP inhibited the phosphorylation of phosphatidylinositol 3-kinase (PI3K), AKT, and nuclear factor (NF)-κB in the GM-CSF-stimulated neutrophils-like dHL-60 cells.
Conclusions:
Therefore, these results reveal for the first time that TRYP inhibits OSM release via the down-regulation of PI3K-AKT-NF-κB axis from neutrophils, presenting its potential as a therapeutic agent for inflammatory responses.
Insights
Tryptanthrin (TRYP) effectively inhibits Oncostatin M (OSM) release from neutrophils by down-regulating the PI3K-AKT-NF-κB pathway. This natural compound shows potential for treating inflammatory conditions.
Area of Science:
- Immunology
- Pharmacology
- Natural Products Chemistry
Background:
- Oncostatin M (OSM) plays a role in inflammatory responses.
- Tryptanthrin (TRYP) is a bioactive alkaloid from indigo plants.
Purpose of the Study:
- To investigate TRYP's inhibitory activity on OSM release from neutrophils.
- To explore TRYP's effects on neutrophils-like differentiated (d)HL-60 cells and mouse bone marrow neutrophils.
Main Methods:
- Stimulation of neutrophils-like dHL-60 cells and mouse neutrophils with granulocyte-macrophage colony-stimulating factor (GM-CSF).
- Assessment of OSM production and mRNA expression levels.
- Analysis of signaling pathway phosphorylation, including PI3K, AKT, and NF-κB.
Main Results:
- TRYP reduced OSM production and mRNA expression in GM-CSF-stimulated neutrophils-like dHL-60 cells.
- TRYP decreased OSM production in GM-CSF-stimulated mouse bone marrow neutrophils.
- TRYP inhibited the phosphorylation of PI3K, AKT, and NF-κB in stimulated neutrophils-like dHL-60 cells.
Conclusions:
- TRYP inhibits OSM release from neutrophils by down-regulating the PI3K-AKT-NF-κB signaling pathway.
- TRYP demonstrates potential as a therapeutic agent for inflammatory diseases.
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