Geniposide protects pulmonary arterial smooth muscle cells from lipopolysaccharide‑induced injury via α7nAchR‑mediated TLR‑4/MyD88 signaling
| Autor: | Bo Zhang, Deng-Feng Zhou, San-Ying Shen, Hong-Fei Zhu, Li-Quan Ren, Xiao-Qin Tan, Yong-Hua Xie, Hui-Dong Chen |
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| Rok vydání: | 2021 |
| Předmět: |
α7 nicotinic acetylcholine receptor
Methyllycaconitine Cancer Research Oncogene Lipopolysaccharide medicine.medical_treatment Inflammation Articles General Medicine Lung injury Pharmacology lipopolysaccharides geniposide chemistry.chemical_compound Cytokine Immunology and Microbiology (miscellaneous) chemistry Downregulation and upregulation Apoptosis medicine medicine.symptom pulmonary artery smooth muscle cells |
| Zdroj: | Experimental and Therapeutic Medicine |
| ISSN: | 1792-1015 1792-0981 |
| DOI: | 10.3892/etm.2021.10668 |
| Popis: | Geniposide is a bioactive iridoid glucoside derived from Gardenia jasminoides that has proven anti-inflammatory effects against acute lung injury. The aim of this study was to determine whether geniposide could protect pulmonary arterial smooth muscle cells (PASMCs) from lipopolysaccharide (LPS)-induced injury and to explore the participation of α7 nicotinic acetylcholine receptor (α7nAChR), which was previously reported to suppress pro-inflammatory cytokine production in LPS-stimulated macrophages. In the present study, rat PASMCs were isolated and stimulated using LPS. The effect of geniposide on LPS-induced PASMC injury was then explored. Geniposide exerted anti-apoptotic and anti-inflammatory effects on LPS-treated PASMCs, as demonstrated by the downregulation of pro-apoptotic proteins and pro-inflammatory cytokines, respectively. Furthermore, the α7nAChR agonist PNU282987 accentuated the protective effect of geniposide against LPS-induced injury in PASMCs by inhibiting toll-like receptor-4/myeloid differentiation primary response 88 (TLR-4/MyD88) signaling and downregulating nuclear factor (NF)-κB expression. Conversely, methyllycaconitine, an inhibitor of α7nAChR, attenuated the effects of geniposide. These findings collectively suggested that in conjunction with geniposide, the activation of α7nAChR may contribute to further mitigating LPS-induced PASMC apoptosis and inflammation. In addition, the underlying mechanisms critically involve the NF-κB/MyD88 signaling axis. These results may provide novel insights into the treatment and management of lung diseases via geniposide administration. |
| Databáze: | OpenAIRE |
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