Mengfei Ma, Jianxun Guo, Xiaoying Su, Baocai Ma, Xiufen Wang, Mingyu Wangshao, Kai Zhong, Yueying Wang, Guoyu Yang, Yingqian Han
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引用次数: 0
Abstract
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.
期刊介绍：
Inflammation Research (IR) publishes peer-reviewed papers on all aspects of inflammation and related fields including histopathology, immunological mechanisms, gene expression, mediators, experimental models, clinical investigations and the effect of drugs. Related fields are broadly defined and include for instance, allergy and asthma, shock, pain, joint damage, skin disease as well as clinical trials of relevant drugs.
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