Saponin attenuates diesel exhaust particle (DEP)-induced MUC5AC expression and pro-inflammatory cytokine upregulation via TLR4/TRIF/NF-κB signaling pathway in airway epithelium and ovalbumin (OVA)-sensitized mice

皂苷通过 TLR4/TRIF/NF-κB 信号通路减弱呼吸道上皮和卵清蛋白 (OVA) 致敏小鼠中柴油机尾气颗粒 (DEP) 诱导的 MUC5AC 表达和促炎细胞因子上调

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作者:Sooyeon Jo, Hyung Gyun Na, Yoon Seok Choi, Chang Hoon Bae, Si-Youn Song, Yong-Dae Kim

Background

Diesel exhaust particle (DEP) is a harmful kind of particulate matter known to exacerbate pre-existing respiratory diseases. Although their adverse effects on airway pathologies have been widely studied, the mechanistic analysis of signaling pathways and potential targets in reducing DEP-induced mucin secretion and pro-inflammatory cytokine production remain elusive. We, for the first time, investigated the effects of Korean Red Ginseng (KRG) extracts on mucin overproduction and airway inflammation induced by DEP.

Conclusion

Our study revealed that KRG extracts have inhibitory effects on DEP-induced expression of MUC5AC and the production of pro-inflammatory cytokines. This finding provides novel insights into the mechanism by which saponin alleviates diesel-susceptible airway inflammation, elucidating its potential as a phytotherapeutic agent for inflammatory pathologies of airway.

Methods

The effects of KRG and saponin on DEP-induced expression of MUC5AC and interleukin (IL)-6/8 were examined by real-time polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay (ELISA) in human airway epithelial NCI-H292 cells. We conducted Western blotting analysis to analyze the associated signaling pathways. To evaluate the effects of saponin treatment on DEP-induced MUC5AC expression and inflammatory cell infiltrations in ovalbumin (OVA)-sensitized mice, immunohistochemical (IHC) staining and real-time PCR were implemented.

Results

The KRG extracts markedly attenuated DEP-induced MUC5AC expression in vitro by inhibiting the TLR4/TRIF/NF-κB pathway. Furthermore, KRG and saponin inhibited DEP-induced pro-inflammatory cytokine IL-6/8 production. The in vivo study revealed that saponin blocked DEP-induced inflammation, mucin production and MUC5AC expression.

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