Effect of the Lipoxin Receptor Agonist BML-111 on Cigarette Smoke Extract-Induced Macrophage Polarization and Inflammation in RAW264.7 Cells.

Abstract

Background:

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.

• Authors: En Cao, Jun Xu, Yuanqi Gong, Jingjing Yuan, Anbang Chen, Jiayi Liu, Yunfei Fan, Xiangyang Fan, Xiaodong Kuang
• Journal: International journal of chronic obstructive pulmonary disease (Int J Chron Obstruct Pulmon Dis) Vol. 18 Pg. 919-932 ( 2023) ISSN: 1178-2005 [Electronic] New Zealand
• PMID: 37229441 (Publication Type: Journal Article)
• Copyright: © 2023 Cao et al.

Chemical References

• Interleukin-10
• Interleukin-18
• 5(S),6(R)-7-trihydroxyheptanoic acid, methyl ester
• Lipoxins
• Tumor Necrosis Factor-alpha
• Cytokines

Topics

• Pulmonary Disease, Chronic Obstructive (drug therapy, prevention & control, metabolism)
• Interleukin-10
• Interleukin-18 (metabolism, pharmacology)
• Lipoxins (metabolism, pharmacology)
• Tumor Necrosis Factor-alpha (metabolism)
• Cigarette Smoking
• Macrophages
• Inflammation (drug therapy, prevention & control, metabolism)
• Cytokines (metabolism)
• Nicotiana