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Published on: July 28, 2016
The role and mechanism of myeloperoxidase in dermatomyositis
Lijuan Zhao1, Chuyu Shen2, Shasha Xie3
1Department of Nephrology and Rheumatology, The Third Xiangya Hospital of Central South University, Changsha, PR China; Department of Rheumatology, Xiangya Hospital of Central South University, Changsha, PR China.
Objective:
Dermatomyositis (DM) is the best known subtype of idiopathic inflammatory myopathies. The hallmarks of DM muscle pathology including microangiopathy, inflammatory infiltration, and perifascicular atrophy. Recent findings have revealed pathogenetic effects of myeloperoxidase (MPO) by causing oxidative damage and regulating abnormal immunity in multiple disease conditions. In this study, we aimed to explore the role of MPO in the pathogenesis of DM.
Methods:
The peripheral blood mononuclear cell (PBMC) mRNA expression and DNA methylation of MPO were verified using real-time qPCR and bisulfite pyrosequencing, respectively. Plasma MPO levels were measured with enzyme-linked immunosorbent assay, and their relationships with clinical characteristics were analyzed. The expression and distribution of MPO in muscle were tested by immunofluorescence. Purified human native MPO protein was used to stimulate human dermal microvascular endothelial cells (HDMECs) and skeletal muscle myotubes. The cell viability, tube forming capacity, permeability, adhesion molecule expressions in HDMECs, and atrophy and programmed cell death pathways in myotubes were then observed.
Results:
MPO gene methylation was decreased, while mRNA expression and plasma levels were increased in DM. Plasma MPO of DM patients was positively correlated with serum creatine kinase (CK). MPO mainly distributed around endomysia capillaries and perifascicular atrophy in DM muscle biopsies, and was co-localized with CD4+, CD8+ T cells and CD19+ B cells. MPO not only could influence the cell viability, tube forming capacity, permeability and expression of adhesion molecules (including ICAM 1, VCAM 1 and E-selectin) of HDMECs, but also could cause atrophy of myotubes.
Conclusions:
Our study disclosed, for the first time, that MPO plays an important role in promoting inflammatory infiltration and inducing muscle damage in DM patients. MPO may be a potential biomarker for DM muscle involvement and MPO targeted drugs may be promising in DM treatment.
Insights
Myeloperoxidase (MPO) is implicated in dermatomyositis (DM) pathogenesis. Increased MPO levels and expression in DM patients promote inflammation and muscle damage, suggesting MPO as a potential therapeutic target.
Area of Science:
- Immunology
- Pathology
- Molecular Biology
Background:
- Dermatomyositis (DM) is a key idiopathic inflammatory myopathy characterized by microangiopathy, inflammation, and atrophy.
- Myeloperoxidase (MPO) is increasingly recognized for its role in oxidative damage and immune dysregulation across various conditions.
Purpose of the Study:
- To investigate the specific role of myeloperoxidase (MPO) in the pathogenesis of dermatomyositis (DM).
Main Methods:
- Assessed MPO mRNA expression and DNA methylation in PBMCs via qPCR and bisulfite pyrosequencing.
- Measured plasma MPO levels using ELISA and correlated them with clinical DM characteristics.
- Examined MPO expression and localization in muscle biopsies using immunofluorescence.
- Investigated MPO effects on human dermal microvascular endothelial cells and skeletal muscle myotubes in vitro.
Main Results:
- DM patients exhibited decreased MPO gene methylation, increased mRNA expression, and elevated plasma MPO levels, correlating positively with serum creatine kinase.
- MPO localized to capillaries and perifascicular areas in DM muscle, co-localizing with T cells and B cells.
- MPO impaired endothelial cell function and induced myotube atrophy in vitro.
Conclusions:
- Myeloperoxidase (MPO) significantly contributes to inflammatory infiltration and muscle damage in dermatomyositis (DM).
- MPO presents as a potential biomarker for DM muscle involvement.
- Targeting MPO may offer a promising therapeutic strategy for DM treatment.
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