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Biochemical pharmacology

Biochemical pharmacology

IF: 5.3
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Inhibition of macrophage extracellular traps by Metrnl/IL-41 suppresses airway remodeling in asthma

Published:28 August 2025 DOI: 10.1016/j.bcp.2025.117288
Kangni Feng , Jiemei Cen , Chunyan He, Xiaoling Zou, Hailing Yang, Yusen Lin, Hongtao Li, Tiantuo Zhang

Abstract

Macrophage extracellular traps (METs) are crucial for initiating airway inflammation and modulating the immune microenvironment of asthmatic airways. Metrnl/IL-41 is a negative regulator of airway inflammatory responses. However, the role of Metrnl/IL-41 in the cross-talk between METs and airway epithelial cells, as well as its effect on the pathophysiology of asthma airway remodeling, are still unclear. We aimed to elucidate the role of METs and Metrnl/IL-41 in airway epithelial cells and chronic asthma. Immunofluorescence and scanning electron microscopy were used to visualize METs formation. The effects of Metrnl/IL-41 on the proliferation, epithelial?mesenchymal transition (EMT), and migration of METs-treated 16-HBE cells were determined. The role of Metrnl/IL-41 in macrophage polarization was analyzed. A chronic asthmatic murine model was established to explore the effects of rm-Metrnl/IL-41 and budesonide on lung histopathology changes, airway hyperresponsiveness, and airway inflammation and airway remodeling. Exposure to house dust mite (HDM) induced METs production in macrophages. Metrnl/IL-41 partially abrogated METs-mediated migration and EMT in 16-HBE cells by inhibiting the nuclear factor-κB (NF-κB) and extracellular signal-regulated kinase 1/2 (ERK1/2) signaling pathways. Rm-Metrnl/IL-41 reduced airway inflammation, airway hyperresponsiveness, mucus secretion, collagen deposition, transforming growth factor-β1 (TGF-β1) levels, and EMT-related protein levels in asthmatic mice. Additionally, Metrnl/IL-41 significantly reduced neutrophils, M1 macrophages, and Th17 cells numbers in the lungs of asthmatic mice. METs play critical roles in EMT and airway remodeling, inhibiting METs formation may constitute a prospective therapeutic approach for asthma. Metrnl/IL-41 is a crucial protective cytokine against airway inflammation, indicating its potential as a therapeutic target in asthma.

Substances (8)

Materials
Procduct Name CAS Molecular Formula Supplier Price
PD 98059 167869-21-8 C16H13NO3 289 suppliers $14.00-$71316.00
PD 98059 167869-21-8 C16H13NO3 289 suppliers $14.00-$71316.00
PD 98059 167869-21-8 C16H13NO3 289 suppliers $14.00-$71316.00
PD 98059 167869-21-8 C16H13NO3 289 suppliers $14.00-$71316.00
BAY 11-7082 19542-67-7 C10H9NO2S 255 suppliers $14.00-$2304.00
BAY 11-7082 19542-67-7 C10H9NO2S 255 suppliers $14.00-$2304.00
BAY 11-7082 19542-67-7 C10H9NO2S 255 suppliers $14.00-$2304.00
BAY 11-7082 19542-67-7 C10H9NO2S 255 suppliers $14.00-$2304.00

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