# Stigmasterol Decreases Oncostatin M Production Through Suppressing PI3K/Akt/NF-κB Signaling Processes in Neutrophil-like Differentiated HL-60 Cells

## TL;DR

Stigmasterol, a plant sterol, reduces inflammation by lowering OSM production in neutrophil-like cells through a specific signaling pathway.

## Contribution

The study reveals a novel mechanism by which stigmasterol suppresses OSM production via the PI3K/Akt/NF-κB pathway in neutrophil-like cells.

## Key findings

- Stigmasterol pretreatment reduces OSM mRNA and protein levels in GM-CSF-stimulated dHL-60 cells.
- Stigmasterol inhibits phosphorylation of PI3K, Akt, and NF-κB, suggesting suppression of the signaling pathway.
- The highest stigmasterol dose (2 µg/mL) shows the most significant inhibitory effect on OSM production.

## Abstract

Background: Cytokine oncostatin M (OSM) is implicated in inflammatory conditions. The plant sterol stigmasterol (ST) is found in diverse plant foods and exerts various benefits, such as antitumor, antioxidant, and anti-inflammatory effects. However, the inhibitory mechanism of ST on OSM production in neutrophils needs to be elucidated. Methods: To evaluate the modulatory effects of ST, this investigation employed neutrophil-like differentiated (d)HL-60 cells. ELISA, real-time PCR, Western blotting, and immunofluorescence staining were conducted. dHL-60 cells were pretreated with ST (0.02 to 2 µg/mL) for 1 h, and then stimulated with GM-CSF (5 ng/mL). Results: Our results showed that addition of granulocyte–macrophage colony-stimulating factor (GM-CSF) leads to up-regulation of OSM mRNA and protein in dHL-60 cells, while pretreatment with ST reduces OSM mRNA and protein levels. Mechanistically, the highest dose (2 µg/mL) of ST significantly decreased phosphorylation of phosphatidylinositol 3-kinase, protein kinase B (Akt), and nuclear factor-κB. Conclusions: Our findings suggest that the plant sterol ST shows potential and warrants in vivo validation on OSM regulation via suppressing PI3K/Akt/NF-κB Signaling Processes.