Expression of Calcium-Binding Proteins MRP8 and MRP14 in Inflammatory Muscle Diseases

Abstract

The pathophysiological role of infiltrating macrophages and their subtypes in idiopathic inflammatory myopathies such as dermatomyositis, polymyositis, and inclusion body myositis is not fully clear. Monocytes exhibit various phenotypes with different functional properties such as release of pro-or anti-inflammatory mediators. Expression of myeloid-related proteins MRP8 and MRP14, two calcium-binding S100-proteins, characterizes a proinflammatory subtype of macrophages. We immunohistochemically investigated expression of MRP8 and MRP14 in muscle biopsies of 33 patients with dermatomyositis, polymyositis, and inclusion body myositis. We found a clear association of expression of MRP8 and MRP14 by infiltrating macrophages with degeneration of myofibers. Because MRP8 and MRP14 are secreted by activated macrophages we investigated if these proteins would have direct extracellular effects on myocytes. We found that the purified MRP8/MRP14 complex inhibited proliferation and differentiation of C2C12 myoblasts and that it induced apoptosis via activation of caspase-3 in a time-and dose-dependent manner. These results indicate that in the course of inflammatory myopathies, activated macrophages can promote destruction and impair regeneration of myocytes via secretion of MRP8/MRP14. Myositis is a term describing muscle inflammation independent of its etiology. The heterogeneous group of acute and chronic idiopathic inflammatory myopathies (IM) is histologically characterized by signs of destruction and partial regeneration of inflamed muscle fibers.

Enhanced Expression of Myeloid-Related Protein Complex (MRP8/14) in Macrophages and Multinucleated Giant Cells in Granulomas of Patients With Active Cardiac Sarcoidosis

“…12,[23][24][25][26][27][28][29][30][31][32] Patients with diabetes mellitus have high plasma levels of MRP8/14. 33 Most recently, it has been reported that increasing plasma concentrations of MRP8/14 among healthy individuals can predict the risk of future cardiovascular events.…”

Alarmins: awaiting a clinical response

“…For example, activated macrophages promote destruction and impair regeneration via secretion of S100A8 and S100A9 in inflammatory muscle diseases (135), and blockade of RAGE restores effective cutaneous wound healing in diabetic mice (136). …”

An iTRAQ approach to quantitative proteome analysis of cerebrospinal fluid from patients with tuberculous meningitis

“…S100A8 belongs to the S100 protein family and originates from neutrophil granulocytes and macrophages. This protein favors cell growth and restrains proliferation, has the ability to mediate apoptosis and enzymatic activity, promotes a dynamic cytoskeleton, maintains calcium ion stability, and stimulates the development of cancer (15,16). In recent years, S100A8 has been found to be able to regulate inflammatory activity and S100A8 is overexpressed in many infectious diseases (17).…”