The role and mechanism of myeloperoxidase in dermatomyositis

Lijuan Zhao; Chuyu Shen; Shasha Xie; Junyu Zhou; Huali Zhang; Honglin Zhu; Yisha Li; Siming Gao

doi:10.1016/j.intimp.2023.110803

The role and mechanism of myeloperoxidase in dermatomyositis

Int Immunopharmacol. 2023 Nov;124(Pt A):110803. doi: 10.1016/j.intimp.2023.110803. Epub 2023 Aug 23.

Authors

Lijuan Zhao¹, Chuyu Shen², Shasha Xie³, Junyu Zhou³, Huali Zhang⁴, Honglin Zhu³, Yisha Li⁵, Siming Gao⁶

Affiliations

¹ Department 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.
² Department of Rheumatology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, PR China.
³ Department of Rheumatology, Xiangya Hospital of Central South University, Changsha, PR China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital of Central South University, Changsha, PR China; Provincial Clinical Research Center for Rheumatic and Immunologic Diseases, Xiangya Hospital of Central South University, Changsha, PR China.
⁴ Department of Pathophysiology, School of Basic Medicine Science, Central South University, Changsha, PR China.
⁵ Department of Rheumatology, Xiangya Hospital of Central South University, Changsha, PR China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital of Central South University, Changsha, PR China; Provincial Clinical Research Center for Rheumatic and Immunologic Diseases, Xiangya Hospital of Central South University, Changsha, PR China. Electronic address: liyisha@csu.edu.cn.
⁶ Department of Rheumatology, Beijing Jishuitan Hospital, Capital Medical University, Beijing, PR China. Electronic address: gaosiming.hurry@163.com.

PMID: 37625367
DOI: 10.1016/j.intimp.2023.110803

Abstract

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.

Keywords: Dermatomyositis; Inflammatory cell migration; Muscle atrophy; Myeloperoxidase; Vascular permeability.