title: 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.
authors.affiliation: Institute of Experimental Dermatology, Department of Pediatrics, University Hospital, Aachen, Germany.
authors.forename: Stephan
authors.initials: S
authors.lastname: Seeliger
authors.forename: Thomas
authors.initials: T
authors.lastname: Vogl
authors.forename: Ingo Hubert
authors.initials: IH
authors.lastname: Engels
authors.forename: J Michael
authors.initials: JM
authors.lastname: Schröder
authors.forename: Clemens
authors.initials: C
authors.lastname: Sorg
authors.forename: Cord
authors.initials: C
authors.lastname: Sunderkötter
authors.forename: Johannes
authors.initials: J
authors.lastname: Roth
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D040501:Calgranulin A / Q000378:metabolism*; D040502:Calgranulin B / Q000378:metabolism* / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D003882:Dermatomyositis / Q000378:metabolism*; D004338:Drug Combinations; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D032446:Myoblasts / Q000166:cytology / Q000502:physiology; D009220:Myositis / Q000378:metabolism*; D018979:Myositis, Inclusion Body / Q000378:metabolism*; D017285:Polymyositis / Q000378:metabolism*
chemical_list: D040501:Calgranulin A; D040502:Calgranulin B; D004338:Drug Combinations