Antroquinonol reduces IL-1β production in macrophages through enhancing the DNA methylation of Tlr4

TL;DR

Antroquinonol, a compound from Antrodia camphorata, reduces inflammation in piglet macrophages by increasing DNA methylation of Tlr4, offering a new way to improve immune function in swine.

Contribution

This study reveals a novel mechanism by which Antroquinonol suppresses IL-1β production via DNA methylation of Tlr4 in macrophages.

Findings

Antroquinonol enhances DNA methyltransferase activity, leading to methylation of Tlr4.

DNA methylation of Tlr4 inhibits NF-κB signaling and reduces IL-1β production in M1 macrophages.

The findings support using Antrodia camphorata fermentation products as immune-boosting feed additives in swine.

Abstract

Macrophages represent one of the most pivotal immune cells in the innate immune responses of weaned piglets. Emerging studies have revealed that numerous plant- or fungal-derived extracts significantly modulate macrophage functions. Antroquinonol (Antro), a characteristic triterpenoid compound isolated from Antrodia camphorata, has been extensively documented for its anti-inflammatory properties, but the precise mechanisms remain unclear.

In this study, we established a macrophage polarization model in vitro, and evaluated the impact of Antro on inflammatory cytokine production in M1 macrophages. The expression of inflammatory pathway components was then measured to identify the specific targets regulated by Antro, and genetic manipulation approaches were further applied to validate these targets.

Antro enhances the enzymatic activities of DNA methyltransferases and facilitates DNA methylation-mediated suppression of Tlr4 expression, thereby inhibiting NF-κB signaling, ultimately attenuating IL-1β production in macrophages.

Our study elucidates a multi-pathway for the anti-inflammatory effects of Antro, significantly enriching the theoretical framework of natural product-mediated immunomodulation (particularly plant/fungal extracts). These findings provide critical scientific support for developing A. camphorata-derived fermentation products as novel feed additives to enhance immune function in swine production.

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