Effect of the Lipoxin Receptor Agonist BML-111 on Cigarette Smoke Extract-Induced Macrophage Polarization and Inflammation in RAW264.7 Cells
En Cao,1,* Jun Xu,1,* Yuanqi Gong,2,* Jingjing Yuan,3 Anbang Chen,1 Jiayi Liu,4 Yunfei Fan,4 Xiangyang Fan,4 Xiaodong Kuang1 1Department of Pathology, Basic Medical College of Nanchang University, Nanchang, Jiangxi, People’s Republic of China; 2Department of Critical Care Med...
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| Format: | Article |
| Language: | English |
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Dove Medical Press
2023-05-01
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| Series: | International Journal of COPD |
| Subjects: | |
| Online Access: | https://www.dovepress.com/effect-of-the-lipoxin-receptor-agonist-bml-111-on-cigarette-smoke-extr-peer-reviewed-fulltext-article-COPD |
| _version_ | 1797822584852578304 |
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| author | Cao E Xu J Gong Y Yuan J Chen A Liu J Fan Y Fan X Kuang X |
| author_facet | Cao E Xu J Gong Y Yuan J Chen A Liu J Fan Y Fan X Kuang X |
| author_sort | Cao E |
| collection | DOAJ |
| description | En Cao,1,* Jun Xu,1,* Yuanqi Gong,2,* Jingjing Yuan,3 Anbang Chen,1 Jiayi Liu,4 Yunfei Fan,4 Xiangyang Fan,4 Xiaodong Kuang1 1Department of Pathology, Basic Medical College of Nanchang University, Nanchang, Jiangxi, People’s Republic of China; 2Department of Critical Care Medicine/ICU (Intensive Care Unit), Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, People’s Republic of China; 3Department of Physiology, School of Basic Medicine, Nanchang University, Nanchang, Jiangxi, People’s Republic of China; 4The Basic Medical School of Nanchang University, Nanchang, Jiangxi, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiaodong Kuang, Department of Pathology, Basic Medical College of Nanchang University, Nanchang, Jiangxi, People’s Republic of China, Email xdssmu2005@163.comBackground: Macrophages are known to play a crucial role in the chronic inflammation associated with Chronic Obstructive Pulmonary Disease (COPD). BML-111, acting as a lipoxin A4 (LXA4) receptor agonist, has shown to be effective in protecting against COPD. However, the precise mechanism by which BML-111 exerts its protective effect remains unclear.Methods: In order to establish a cell model of inflammation, cigarette smoke extract (CSE) was used on the RAW264.7 cell line. Afterwards, an Enzyme-linked immunosorbent assay (ELISA) kit was employed to measure concentrations of tumor necrosis factor-α (TNF-α), interleukin-1beta (IL-1β), interleukin-18 (IL-18), and interleukin-10 (IL-10) in the cell supernatants of the RAW264.7 cells.In this study, we examined the markers of macrophage polarization using two methods: quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot analysis. Additionally, we detected the expression of Notch-1 and Hes-1 through Western blotting.Results: BML-111 effectively suppressed the expression of pro-inflammatory cytokines TNF-α, IL-1β, and IL-18, as well as inflammasome factors NLRP3 and Caspase-1, while simultaneously up-regulating the expression of the anti-inflammatory cytokine IL-10 induced by CSE. Moreover, BML-111 reduced the expression of iNOS, which is associated with M1 macrophage polarization, and increased the expression of Arg-1, which is associated with M2 phenotype. Additionally, BML-111 downregulated the expression of Hes-1 and the ratio of activated Notch-1 to Notch-1 induced by CSE. The effect of BML-111 on inflammation and macrophage polarization was reversed upon administration of the Notch-1 signaling pathway agonist Jagged1.Conclusion: BML-111 has the potential to suppress inflammation and modulate M1/M2 macrophage polarization in RAW264.7 cells. The underlying mechanism may involve the Notch-1 signaling pathway.Keywords: BML-111, macrophage polarization, Notch-1 signaling pathway, COPD |
| first_indexed | 2024-03-13T10:10:15Z |
| format | Article |
| id | doaj.art-1c0cdedd33904905a4c3b1b1eb8b6fa9 |
| institution | Directory Open Access Journal |
| issn | 1178-2005 |
| language | English |
| last_indexed | 2024-03-13T10:10:15Z |
| publishDate | 2023-05-01 |
| publisher | Dove Medical Press |
| record_format | Article |
| series | International Journal of COPD |
| spelling | doaj.art-1c0cdedd33904905a4c3b1b1eb8b6fa92023-05-21T16:29:55ZengDove Medical PressInternational Journal of COPD1178-20052023-05-01Volume 1891993283870Effect of the Lipoxin Receptor Agonist BML-111 on Cigarette Smoke Extract-Induced Macrophage Polarization and Inflammation in RAW264.7 CellsCao EXu JGong YYuan JChen ALiu JFan YFan XKuang XEn Cao,1,* Jun Xu,1,* Yuanqi Gong,2,* Jingjing Yuan,3 Anbang Chen,1 Jiayi Liu,4 Yunfei Fan,4 Xiangyang Fan,4 Xiaodong Kuang1 1Department of Pathology, Basic Medical College of Nanchang University, Nanchang, Jiangxi, People’s Republic of China; 2Department of Critical Care Medicine/ICU (Intensive Care Unit), Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, People’s Republic of China; 3Department of Physiology, School of Basic Medicine, Nanchang University, Nanchang, Jiangxi, People’s Republic of China; 4The Basic Medical School of Nanchang University, Nanchang, Jiangxi, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiaodong Kuang, Department of Pathology, Basic Medical College of Nanchang University, Nanchang, Jiangxi, People’s Republic of China, Email xdssmu2005@163.comBackground: Macrophages are known to play a crucial role in the chronic inflammation associated with Chronic Obstructive Pulmonary Disease (COPD). BML-111, acting as a lipoxin A4 (LXA4) receptor agonist, has shown to be effective in protecting against COPD. However, the precise mechanism by which BML-111 exerts its protective effect remains unclear.Methods: In order to establish a cell model of inflammation, cigarette smoke extract (CSE) was used on the RAW264.7 cell line. Afterwards, an Enzyme-linked immunosorbent assay (ELISA) kit was employed to measure concentrations of tumor necrosis factor-α (TNF-α), interleukin-1beta (IL-1β), interleukin-18 (IL-18), and interleukin-10 (IL-10) in the cell supernatants of the RAW264.7 cells.In this study, we examined the markers of macrophage polarization using two methods: quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot analysis. Additionally, we detected the expression of Notch-1 and Hes-1 through Western blotting.Results: BML-111 effectively suppressed the expression of pro-inflammatory cytokines TNF-α, IL-1β, and IL-18, as well as inflammasome factors NLRP3 and Caspase-1, while simultaneously up-regulating the expression of the anti-inflammatory cytokine IL-10 induced by CSE. Moreover, BML-111 reduced the expression of iNOS, which is associated with M1 macrophage polarization, and increased the expression of Arg-1, which is associated with M2 phenotype. Additionally, BML-111 downregulated the expression of Hes-1 and the ratio of activated Notch-1 to Notch-1 induced by CSE. The effect of BML-111 on inflammation and macrophage polarization was reversed upon administration of the Notch-1 signaling pathway agonist Jagged1.Conclusion: BML-111 has the potential to suppress inflammation and modulate M1/M2 macrophage polarization in RAW264.7 cells. The underlying mechanism may involve the Notch-1 signaling pathway.Keywords: BML-111, macrophage polarization, Notch-1 signaling pathway, COPDhttps://www.dovepress.com/effect-of-the-lipoxin-receptor-agonist-bml-111-on-cigarette-smoke-extr-peer-reviewed-fulltext-article-COPDbml-111macrophage polarizationnotch-1 signaling pathwaycopd |
| spellingShingle | Cao E Xu J Gong Y Yuan J Chen A Liu J Fan Y Fan X Kuang X Effect of the Lipoxin Receptor Agonist BML-111 on Cigarette Smoke Extract-Induced Macrophage Polarization and Inflammation in RAW264.7 Cells International Journal of COPD bml-111 macrophage polarization notch-1 signaling pathway copd |
| title | Effect of the Lipoxin Receptor Agonist BML-111 on Cigarette Smoke Extract-Induced Macrophage Polarization and Inflammation in RAW264.7 Cells |
| title_full | Effect of the Lipoxin Receptor Agonist BML-111 on Cigarette Smoke Extract-Induced Macrophage Polarization and Inflammation in RAW264.7 Cells |
| title_fullStr | Effect of the Lipoxin Receptor Agonist BML-111 on Cigarette Smoke Extract-Induced Macrophage Polarization and Inflammation in RAW264.7 Cells |
| title_full_unstemmed | Effect of the Lipoxin Receptor Agonist BML-111 on Cigarette Smoke Extract-Induced Macrophage Polarization and Inflammation in RAW264.7 Cells |
| title_short | Effect of the Lipoxin Receptor Agonist BML-111 on Cigarette Smoke Extract-Induced Macrophage Polarization and Inflammation in RAW264.7 Cells |
| title_sort | effect of the lipoxin receptor agonist bml 111 on cigarette smoke extract induced macrophage polarization and inflammation in raw264 7 cells |
| topic | bml-111 macrophage polarization notch-1 signaling pathway copd |
| url | https://www.dovepress.com/effect-of-the-lipoxin-receptor-agonist-bml-111-on-cigarette-smoke-extr-peer-reviewed-fulltext-article-COPD |
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