Induction of autophagy via the TLR4/NF-?B signaling pathway by astragaloside IV contributes to the amelioration of inflammation in RAW264.7 cells
Induction of autophagy via the TLR4/NF-?B signaling pathway by astragaloside IV contributes to the amelioration of inflammation in RAW264.7 cells
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黄芪甲苷 IV 通过 TLR4/NF-κB 信号通路诱导自噬有助于改善 RAW264.7 细胞的炎症
DOI：
10.1016/j.biopha.2021.111271
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发表时间：
2021-02-06
影响因子：
7.5
通讯作者：
Xiong, Lei
中科院分区：
文献类型：
--
作者：
Ying, Yi;Sun, Chun-bin;Xiong, Lei
吸烟相关的肺损伤是许多呼吸系统疾病最常见和致命的病因之一，目前尚无有效的干预措施。黄芪甲苷 (ASIV) 是从黄芪中提取的活性成分。它被规定用于治疗上呼吸道感染。在这里，我们报告了 ASIV 对暴露于香烟提取物（CSE）的 RAW264.7 细胞的潜在抗炎作用和机制。将小鼠巨噬细胞暴露于 CSE，然后以 25?100 μg/mL 施用 ASIV 24 小时。 ASIV 通过抑制促炎细胞因子的释放来显着挽救 CSE 诱导的细胞死亡。我们通过使用串联 mRFP-GFP-LC3 荧光显微镜分析自噬通量来测量作为细胞内清道夫的自噬。在暴露于 CSE 的 RAW264.7 细胞中给予 ASIV 后，自噬体显着增加，并产生一系列自噬液泡，如透射电子显微镜所见。转染 siRNA 后自噬的丧失加剧了炎症损伤和炎症细胞因子的释放。从机制上讲，ASIV 触发的自噬是由 TLR4/NF-κB 信号通路介导的，以减少炎症。综上所述，我们的研究结果表明 ASIV 可以刺激自噬，并且 ASIV 通过抑制 TLR4/NF-κB 信号通路诱导自噬，从而有助于减轻炎症。
Cigarette smoking-related lung injury is one of the most common and fatal etiologies of many respiratory diseases, for which no effective interventions are available. Astragaloside IV (ASIV) is an active component extracted from Astragalus membranaceus. It is prescribed as a treatment for upper respiratory tract infections. Here, we report the potential anti-inflammatory effects and mechanisms of ASIV on cigarette smoking extract(CSE)-exposed RAW264.7 cells. Murine macrophages were exposed to CSE, followed by administration of ASIV at 25?100 ?g/mL for 24 h. ASIV significantly rescued CSE-induced cell death by inhibition of release pro inflammatory cytokines. We measured autophagy as an intracellular scavenger by analyzing autophagic flux using tandem mRFP-GFP-LC3 fluorescence microscopy. Following administration with ASIV in CSE-exposed RAW264.7 cells, there was a notable increase in autophagosomes and a range of autophagic vacuoles were generated, as seen with transmission electron microscopy. Loss of autophagy following transfection siRNA aggravated inflammatory injury and release of inflammatory cytokines. Mechanistically, ASIV-triggered autophagy is mediated by the TLR4/NF-?B signaling pathway to reduce inflammation. Taken together, our findings suggest that ASIV acts stimulates autophagy, and that ASIV induces autophagy by inhibiting the TLR4/NF-?B signaling pathway, contributing to alleviation of inflammation.