NZ suppresses TLR4/NF-κB signalings and NLRP3 inflammasome activation in LPS-induced RAW264.7 macrophages
Autor: | Hui Wu, Yihua Zhang, Xiaojian Gong, Pengjun Xiang, Tong Chen, Yi Mou, Qinghua Hu, Peng Xie, Guo Lu, Hui Ji |
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Rok vydání: | 2015 |
Předmět: |
Lipopolysaccharides
Lipopolysaccharide Cell Survival Inflammasomes Immunology Caspase 1 Biology Nitric Oxide chemistry.chemical_compound Mice NLR Family Pyrin Domain-Containing 3 Protein medicine Macrophage Animals Oleanolic Acid Pharmacology Anti-Inflammatory Agents Non-Steroidal NF-kappa B Inflammasome NF-κB NFKB1 Molecular biology Toll-Like Receptor 4 RAW 264.7 Cells chemistry Myeloid Differentiation Factor 88 TLR4 Cytokines lipids (amino acids peptides and proteins) Signal transduction Carrier Proteins Reactive Oxygen Species medicine.drug Signal Transduction |
Zdroj: | Inflammation research : official journal of the European Histamine Research Society ... [et al.]. 64(10) |
ISSN: | 1420-908X |
Popis: | Objective The purpose of the present study was to evaluate the potential therapeutic effects of NZ on lipopolysaccharide (LPS)-induced RAW264.7 cells and explore its underlying mechanisms. Methods The effect of NZ on NO generation in LPS-activated macrophage was measured by Griess assay. The concentrations of TNF-α, IL-18, IL-1β were analyzed with ELISA kits. The LPS-induced production of reactive oxygen species (ROS) was determined by flow cytometry. The protein expressions of TLR4, NF-κB and NLRP3 signaling pathway were investigated with Western blot analysis. Results It was shown that NZ significantly reduced the production of NO and the generation of pro-inflammatory cytokines in LPS-induced RAW264.7 cells. In addition, NZ markedly inhibited the up-regulation of toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88) and the activation of nuclear factor kappa B (NF-κB) in LPS-stimulated RAW 264.7 macrophages. Of note, NZ suppressed the expression of the inflammasome component such as NOD-like receptor 3(NLRP3), apoptosis-associated speck-like protein containing CARD(ASC), as well as the levels of cytokines including Interleukin-18(IL-18) and Interleukin-1β(IL-1β). Conclusion These results indicated that NZ inhibited the generations of NO and pro-inflammatory cytokines by suppressing TLR4/MyD88/NF-κB pathway, suggesting that NZ could be an effective candidate for ameliorating LPS-induced inflammatory responses. |
Databáze: | OpenAIRE |
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