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Objective <p>This study investigates the role of the aryl hydrocarbon receptor (AhR) in lipopolysaccharide (LPS)-induced inflammatory responses in IPEC-J2 cells.</p> Methods <p>Inflammatory responses were triggered in IPEC-J2 cells using 5 μg/ml LPS. AhR was activated with tryptophan or FICZ and knocked down via RNA interference. PINK1/Parkin-mediated mitophagy was activated using CCCP and inhibited by PINK1 knockdown. Inflammatory mediators and pathway proteins were analyzed through ELISA, RT-qPCR, western blot, and immunofluorescence. Mitochondrial function was assessed by measuring ROS, ATP, and mitochondrial membrane potential. The interaction between AhR and PINK1 was examined using dual-luciferase reporter assays.</p> Results <p>The IDO1/AhR signaling axis was activated in LPS-stimulated IPEC-J2 cells. AhR activation was found to attenuate LPS-induced inflammatory responses, whereas AhR knockdown exacerbated these responses. Mechanistic investigations demonstrated that AhR activation alleviated LPS-induced mitochondrial damage. Activating PINK1/Parkin-mediated mitophagy successfully countered the increased inflammatory response in IPEC-J2 cells after AhR knockdown. Moreover, blocking PINK1 reversed the anti-inflammatory effects of FICZ. Dual-luciferase reporter assays revealed that AhR acts as a crucial transcription factor by directly binding to the promoter region, thereby initiating PINK1 transcription.</p> Conclusions <p>AhR reduces LPS-induced inflammatory response in IPEC-J2 cells by activating PINK1/Parkin-mediated mitophagy, with AhR directly engaging the PINK1 promoter to enhance its transcription. Targeting AhR may present a novel strategy for the prevention and management of Escherichia coli-induced diarrhea in piglets.</p>

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Aryl hydrocarbon receptor (AhR) alleviates the LPS-induced inflammatory responses in IPEC-J2 cells by activating PINK1/Parkin-mediated mitophagy

  • 期刊论文

  • 发表日期：

    2025年6月30日

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  • Mengfei Ma,
  • Jianxun Guo,
  • Xiaoying Su,
  • Baocai Ma,
  • Xiufen Wang,
  • Mingyu Wangshao,
  • Kai Zhong,
  • Yueying Wang,
  • Guoyu Yang,
  • Yingqian Han

摘要

Objective

This study investigates the role of the aryl hydrocarbon receptor (AhR) in lipopolysaccharide (LPS)-induced inflammatory responses in IPEC-J2 cells.

Methods

Inflammatory responses were triggered in IPEC-J2 cells using 5 μg/ml LPS. AhR was activated with tryptophan or FICZ and knocked down via RNA interference. PINK1/Parkin-mediated mitophagy was activated using CCCP and inhibited by PINK1 knockdown. Inflammatory mediators and pathway proteins were analyzed through ELISA, RT-qPCR, western blot, and immunofluorescence. Mitochondrial function was assessed by measuring ROS, ATP, and mitochondrial membrane potential. The interaction between AhR and PINK1 was examined using dual-luciferase reporter assays.

Results

The IDO1/AhR signaling axis was activated in LPS-stimulated IPEC-J2 cells. AhR activation was found to attenuate LPS-induced inflammatory responses, whereas AhR knockdown exacerbated these responses. Mechanistic investigations demonstrated that AhR activation alleviated LPS-induced mitochondrial damage. Activating PINK1/Parkin-mediated mitophagy successfully countered the increased inflammatory response in IPEC-J2 cells after AhR knockdown. Moreover, blocking PINK1 reversed the anti-inflammatory effects of FICZ. Dual-luciferase reporter assays revealed that AhR acts as a crucial transcription factor by directly binding to the promoter region, thereby initiating PINK1 transcription.

Conclusions

AhR reduces LPS-induced inflammatory response in IPEC-J2 cells by activating PINK1/Parkin-mediated mitophagy, with AhR directly engaging the PINK1 promoter to enhance its transcription. Targeting AhR may present a novel strategy for the prevention and management of Escherichia coli-induced diarrhea in piglets.