Tanshinone IIA inhibits lipopolysaccharide‑induced inflammatory responses through the TLR4/TAK1/NF‑κB signaling pathway in vascular smooth muscle cells
| Autor: | Zhe Meng, Shuai Teng, Chun‑Ying Si, Xin‑Hui Yu, Haiyu Li |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Lipopolysaccharides
Male 0301 basic medicine Vascular smooth muscle Lipopolysaccharide Myocytes Smooth Muscle Down-Regulation Nitric Oxide Synthase Type II Inflammation Nitric Oxide Muscle Smooth Vascular Nitric oxide Proinflammatory cytokine Rats Sprague-Dawley 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Genetics medicine Animals Chemokine CCL2 Cell Death Interleukin-6 Tumor Necrosis Factor-alpha Chemistry NF-kappa B NADPH Oxidases General Medicine MAP Kinase Kinase Kinases Molecular biology Toll-Like Receptor 4 Phenotype 030104 developmental biology 030220 oncology & carcinogenesis Abietanes TLR4 Tumor necrosis factor alpha medicine.symptom Signal transduction Reactive Oxygen Species Signal Transduction |
| Zdroj: | International Journal of Molecular Medicine. |
| ISSN: | 1791-244X 1107-3756 |
| DOI: | 10.3892/ijmm.2019.4100 |
| Popis: | To aim of the present study was to determine whether Tanshinone IIA (Tan IIA) inhibits lipopolysaccharide (LPS)‑induced inflammation in vascular smooth muscle cells (VSMCs) from rats and elucidate the underlying molecular mechanism. VSMCs were primarily cultured and then treated with LPS (1 µg/l) and Tan IIA (25, 50 and 100 µmol/l) for 24 h. Monocyte chemoattractant protein (MCP)‑1, interleukin (IL)‑6 and tumor necrosis factor (TNF)‑α levels were detected by ELISA and reverse transcription‑quantitative polymerase chain reaction. Nitric oxide (NO) production was measured using the Griess reaction. The expression of Toll‑like receptor 4 (TLR4), nuclear factor (NF)‑κB (p65), and inducible NO synthase (iNOS), and the phosphorylation of transforming growth factor‑β‑activated kinase 1 (TAK1) were detected by western blot analysis. Tan IIA inhibited the LPS‑induced expression of MCP‑1, IL‑6, and TNF‑α in a concentration‑dependent manner and inhibited iNOS‑mediated NO production. In addition, Tan IIA suppressed the expression of TLR4, the phosphorylation of TAK1, and the nuclear translocation of NF‑κB (p65). The anti‑TLR4 antibody and TAK1 inhibitor 5Z‑7‑oxozeaenol partially attenuated the LPS‑induced expression of proinflammatory cytokines. In conclusion, Tan IIA inhibits LPS‑induced inflammatory responses in VSMCs in vitro through the partial suppression of the TLR4/TAK1/NF‑κB signaling pathway. |
| Databáze: | OpenAIRE |
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