| Autor: |
Weihong Dai, Shuangqin Yin, Fangjie Wang, Tianyin Kuang, Hongyan Xiao, Wenyuan Kang, Caihong Yun, Fei Wang, Li Luo, Shengxiang Ao, Jing Zhou, Xue Yang, Chao Fan, Wei Li, Dongmei He, He Jin, Wanqi Tang, Lizhu Liu, Rixing Wang, Huaping Liang, Junyu Zhu |
| Jazyk: |
angličtina |
| Rok vydání: |
2024 |
| Předmět: |
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| Zdroj: |
Cell Communication and Signaling, Vol 22, Iss 1, Pp 1-20 (2024) |
| Druh dokumentu: |
article |
| ISSN: |
1478-811X |
| DOI: |
10.1186/s12964-024-01847-9 |
| Popis: |
Abstract Aryl hydrocarbon receptor (AhR) plays an important role in inflammation and immunity as a new therapeutic target for infectious disease and sepsis. Punicalagin (PUN) is a Chinese herbal monomer extract of pomegranate peel that has beneficial anti-inflammatory, antioxidant and anti-infective effects. However, whether PUN is a ligand of AhR, its effect on AhR expression, and its signaling pathway remain poorly understood. In this study, we found that PUN was a unique polyphenolic compound that upregulated AhR expression at the transcriptional level, and regulated the AhR nongenomic pathway. AhR expression in lipopolysaccharide-induced macrophages was upregulated by PUN in vitro and in vivo in a time- and dose-dependent manner. Using specific inhibitors and siRNA, induction of AhR by PUN depended on sequential phosphorylation of 90-kDa ribosomal S6 kinase (p90RSK), which was activated by the mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) and phosphoinositide-dependent protein kinase (PDK)1 pathways. PUN promoted p90RSK-mediated activator protein-1 (AP-1) activation. AhR knockout or inhibitors reversed suppression of interleukin (IL)-6 and IL-1β expression by PUN. PUN decreased Listeria load and increased macrophage survival via AhR upregulation. In conclusion, we identified PUN as a novel selective AhR modulator involved in AhR expression via the MEK/ERK and PDK1 pathways targeting p90RSK/AP-1 in inflammatory macrophages, which inhibited macrophage inflammation and promoted bactericidal activity. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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