Publication: MPO-Mediated oxidative stress regulates lung tissue damage in T-COPD through activation of the NLRP3 inflammasome
Authors
Kaican Zong ; E Jiang ; Chunyan Luo ; Hengyi Chen ; Wen Li
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Publisher
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Universidad de Murcia, Departamento de Biologia Celular e Histiologia
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DOI
https://doi.org/10.14670/HH-25-006
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info:eu-repo/semantics/article
Description
Abstract
urpose. This study aimed to investigate the
role of MPO in regulating the NLRP3 signaling pathway
and its impact on lung injury in a Mycobacterium
tuberculosis-induced chronic obstructive pulmonary
disease (T-COPD) model.
Methods. T-COPD was induced in mice by
stimulating with M. tuberculosis, and lung tissues were
collected for histological analysis. ELISA, qPCR, and
western blot assays were performed to assess the
expression of pro-inflammatory cytokines and markers
of lung injury, including Myeloperoxidase (MPO) and
NOD-like receptor protein 3 (NLRP3). MPO-IN-5, an
MPO inhibitor, was used to treat T-COPD mice, and its
effects on inflammation and lung damage were
evaluated. In vitro, murine lung epithelial MLE-12 cells
were treated with LPS, CSE, and M. tuberculosis with or
without MPO treatment, followed by assessments of cell
viability, apoptosis, ROS levels, and NLRP3 pathway
activity.
Results. Histological analysis of the M. tuberculosis/
COPD group revealed significant pulmonary edema,
inflammatory cell infiltration, and granuloma formation
in the liver and spleen, compared with the COPD group.
Pro-inflammatory cytokines TNF-α, IL-18, and IL-6
were elevated in the blood of the M. tuberculosis/COPD
group. In the lungs, MPO expression and NLRP3
pathway activation were significantly increased.
Treatment with MPO-IN-5 reduced the levels of LDH,
CRP, and PCT, and reversed the morphological and
inflammatory changes in lung tissue. Furthermore,
MPO-IN-5 treatment also significantly decreased ROS
production and the expression of inflammatory
cytokines. In vitro, MPO treatment exacerbated NLRP3
activation in murine lung epithelial MLE-12 cells, while
MPO inhibition (with MPO-IN-5) or NLRP3 knockdown mitigated these effects, enhancing cell
proliferation and reducing apoptosis.
Conclusion. Our results suggest that MPO plays a
critical role in regulating the NLRP3 signaling pathway,
contributing to lung injury in the T-COPD model.
Inhibition of MPO with MPO-IN-5 effectively alleviates
inflammation, reduces oxidative stress, and suppresses
NLRP3 pathway activation, highlighting its potential as
a therapeutic target for T-COPD.
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