期刊
TOXICOLOGY
卷 486, 期 -, 页码 -出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.tox.2023.153430
关键词
Pinellia ternata lectin(PTL); PI3K; Akt; mTOR pathway; TLR4; Inflammation
Pinellia ternata, a traditional Chinese medicine, contains a strong mucosal irritant called Pinellia ternata lectin (PTL). This study found that PTL activates the PI3K/Akt/mTOR and NF-kappa B pathways, leading to inflammation by releasing proinflammatory cytokines. PTL was shown to bind Toll-like receptor 4 (TLR4) and mediate inflammation through the PI3K/Akt/mTOR pathway.
Pinellia ternata, a widely used traditional Chinese medicine, contains a strong mucosal irritant that is connected with Pinellia ternata lectin (PTL) in its tubers. The purpose of this study was to explore the mechanisms by which PTL induces inflammation. We found that in RAW264.7 cells, PTL activated the PI3K/Akt/mTOR and NF-kappa B pathways, which resulted in the release of proinflammatory cytokines. Flow cytometry and laser confocal mi-croscopy analysis showed that FITC-labeled PTL bound to the macrophages' surface. Based on kinetic analyses and protein-protein docking simulations, PTL was shown to bind toll-like receptor 4 (TLR4).it was demonstrated that PTL binds highly to Toll-like receptor 4 (TLR4). TLR4 knock-down or knockout resulted in a decrease in both cytokine release and PI3K/Akt/mTOR and NF-kappa B pathway activation in PTL-stimulated macrophages or mice. RNA-seq analysis showed that genes involved in the PI3K/Akt/mTOR signaling pathway were strongly upre-gulated in response to PTL stimulation, confirming that the PI3K/Akt/mTOR pathway is linked to the inflam-matory effect of PTL in RAW264.7 cells. These findings reveal that PTL can mediate inflammation through TLR4 and activating the PI3K/Akt/mTOR to regulate NF-kappa B signaling pathways.
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