Pinellia ternata lectin induces inflammation through TLR4 receptor and mediates PI3K/Akt/mTOR axis to regulate NF-κB signaling pathway

• DOI: 10.1016/j.tox.2023.153430
• Publication Date: 2023-01-18T15:50:35Z
• Authors: Jinfei Li; Wei Wang; Yuan Yuan; Xiaobing Cui; Huimin Bian; Hongmei Wen; Xingde Zhang; Hongli Yu; Hao Wu
• Keywords: Proinflammatory cytokine; Pinellia ternata

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-κB pathways, which resulted in the release of proinflammatory cytokines. Flow cytometry and laser confocal microscopy 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-κB pathway activation in PTL-stimulated macrophages or mice. RNA-seq analysis showed that genes involved in the PI3K/Akt/mTOR signaling pathway were strongly upregulated in response to PTL stimulation, confirming that the PI3K/Akt/mTOR pathway is linked to the inflammatory 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-κB signaling pathways.