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Myeloid related protein induces muscle derived inflammatory mediators in juvenile dermatomyositis

Kiran Nistala, Hemlata Varsani, Helmut Wittkowski

    Arthritis Research & Therapy
    |November 30, 2013
    PubMed
    Abstract

    Insights

    Myeloid related protein (MRP) 8/14, secreted by macrophages, correlates with juvenile dermatomyositis (JDM) disease activity. This protein may drive JDM myositis by increasing local cytokine production in muscle tissue.

    Area of Science:

    • Immunology
    • Rheumatology
    • Cell Biology

    Background:

    • The pathogenesis of juvenile dermatomyositis (JDM) is not fully understood.
    • The role of monocytes/macrophages in early JDM muscle pathology is unknown.
    • Hypothesized that myeloid related protein (MRP) 8/14 secreted by these cells contributes to JDM muscle pathology.

    Purpose of the Study:

    • To investigate the role of myeloid related protein (MRP) 8/14 in juvenile dermatomyositis (JDM).
    • To assess serum MRP8/14 levels as a potential biomarker for JDM disease activity.
    • To explore the mechanism by which MRP8/14 may contribute to JDM-associated myositis.

    Main Methods:

    • Compared serum MRP8/14 levels with clinical disease activity in 56 JDM patients.
    • Analyzed MRP-expressing cells in muscle biopsies using immunohistochemistry.
    • Investigated the effects of MRP stimulation and endoplasmic reticulum (ER) stress on human myoblasts in vitro.
    • Measured cytokine levels in serum and cell culture supernatants using multiplex immunoassay.

    Main Results:

    • Serum MRP8/14 levels positively correlated with physician's global assessment of JDM activity (R = 0.65, p = 0.0003) and negatively with muscle strength/endurance and CMAS (R = -0.55, p = 0.004).
    • MRP8/14 was expressed by macrophages (CD68+) in JDM muscle tissue.
    • MRP stimulation induced MCP-1 and IL-6 secretion by myoblasts, enhanced by ER stress.
    • Elevated levels of MCP-1 and IL-6 were found in JDM patient serum compared to healthy controls.

    Conclusions:

    • Serum MRP8/14 is a potential biomarker for disease activity in juvenile dermatomyositis (JDM).
    • Tissue-infiltrating macrophages secreting MRP8/14 may contribute to myositis.
    • MRP8/14 may drive JDM pathogenesis by promoting local cytokine production in muscle.

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