1. The anti-inflammatory effect of BML-111 on COPD may be mediated by regulating NLRP3 inflammasome activation and ROS production.
- Author
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Cao Y, Zhou X, Yin Z, Yu X, Yang Q, Guo Q, Tian D, Xiong X, Xu G, and Kuang X
- Subjects
- Animals, Bronchoalveolar Lavage Fluid chemistry, Bronchoalveolar Lavage Fluid cytology, Cytokines metabolism, Inflammasomes metabolism, Leukocyte Count, Lung drug effects, Lung metabolism, Lung pathology, Male, Mice, Pneumonia metabolism, Pneumonia prevention & control, Protective Agents pharmacology, Pulmonary Disease, Chronic Obstructive metabolism, Random Allocation, Anti-Inflammatory Agents pharmacology, Heptanoic Acids pharmacology, Inflammasomes drug effects, NLR Family, Pyrin Domain-Containing 3 Protein metabolism, Pulmonary Disease, Chronic Obstructive prevention & control, Reactive Oxygen Species metabolism
- Abstract
The aim of this study is to investigate whether the lipoxin receptor agonist BML-111 exerts a protective effect against inflammation in a mouse model of chronic obstructive pulmonary disease (COPD) by regulating NLRP3 inflammasome activation and reactive oxygen species (ROS) production. In this study, mice were randomly divided into the following five groups: control group (Control), COPD model group (Model), BML-111 low-dose group (Low-BML), BML-111 high-dose group (High-BML) and Dexamethasone group (Dex). NLRP3 involvement and oxidative stress were evaluated. Differential cell counts in the BALF were calculated to obtain a reliable enumeration of each cell type, and the levels of TGF-β, TNF-α, IL-1β, and IL-10 in BALF were evaluated using ELISA. We found that the white blood cell and lymphocyte numbers in the BALF were significantly lower in the High-BML group than in the Model group. ELISA of the BALF showed that BML-111 reduced TGF-β and IL-1β levels to some extent. HE staining showed various degrees of reduction in inflammatory cell infiltration in the bronchopulmonary tissue and blood vessels of the Low-BML, High-BML and Dex groups. Measurement of oxidative stress showed that SOD activity was significantly upregulated and that the increase in MDA content was prevented in the High-BML and Dex groups. According to the Western blotting analysis, the levels of NLRP3, Cleaved-IL-1β and Cleaved-caspase-1 were decreased and Nrf-2 was increased to various extents in the Low-BML, High-BML and Dex groups. Based on these findings, BML-111 may prevent NLRP3 inflammasome activation and inhibit ROS production via upregulation of Nrf-2, thereby exerting an anti-inflammatory effect on COPD model mice., (Copyright © 2018 Elsevier Inc. All rights reserved.)
- Published
- 2018
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