Induction of autophagy via the TLR4/NF-κB signaling pathway by astragaloside Ⅳ contributes to the amelioration of inflammation in RAW264.7 cells
| Autor: | Jing Wen, Si-si Han, Chun-Bin Sun, Jiong Hou, Zhong-shan Yang, Fei-yu Liu, Bo-jun Chen, Si-qi Zhang, Jin-Yuan Yan, Lei Xiong, Yi Ying, Jing-ze Yu |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Programmed cell death Anti-Inflammatory Agents Inflammation Vacuole RM1-950 Lung injury Proinflammatory cytokine 03 medical and health sciences Mice 0302 clinical medicine medicine Autophagy Animals Phosphorylation Pharmacology Chemistry Macrophages NF-kappa B General Medicine Saponins Triterpenes Toll-Like Receptor 4 030104 developmental biology RAW 264.7 Cells Astragaloside Ⅳ 030220 oncology & carcinogenesis Cancer research TLR4 Cytokines Therapeutics. Pharmacology medicine.symptom Signal transduction Signal Transduction TLR4/NF-κB signaling pathway |
| Zdroj: | Biomedicine & Pharmacotherapy, Vol 137, Iss, Pp 111271-(2021) |
| ISSN: | 0753-3322 |
| Popis: | 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 μg/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-κB 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-κB signaling pathway, contributing to alleviation of inflammation. |
| Databáze: | OpenAIRE |
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