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Immunolocalization of interleukin-1 receptors in the sarcolemma and nuclei of skeletal muscle in patients with idiopathic inflammatory myopathies

Grundtman C, Salomonsson S, Dorph C +3 more2007Arthritis & RheumatismJournal Article
Immune/InnateMusculoskeletal

Abstract

ObjectiveInterleukin‐1 (IL‐1) acts via its receptors to induce gene expression that mediates protein synthesis involved in inflammation. Increased expression of IL‐1α and IL‐1β in muscle tissue from patients with polymyositis and dermatomyositis has been demonstrated. It is not known whether the reciprocal IL‐1 receptors are expressed in human muscle tissue. The purpose of this study was to investigate the expression of IL‐1 receptors and their ligands in muscle tissue from patients with myositis and from healthy controls.MethodsMuscle biopsy tissues from 10 patients with polymyositis or dermatomyositis and 7 healthy control subjects were investigated by immunohistochemistry using antibodies against IL‐1 receptor type I (IL‐1RI), IL‐1RII, IL‐1α, IL‐1β, and IL‐1 receptor antagonist (IL‐1Ra). Quantification was performed by computerized image analysis, and localization of expression was determined by double staining using immunofluorescence and confocal microscopy.ResultsIn tissue samples from the patients, IL‐1RI and IL‐1RII were expressed in muscle fibers, inflammatory cells, and endothelial cells. Expression in muscle fibers was localized to the sarcolemma and nuclei. IL‐1α was expressed in endothelial cells and inflammatory cells, whereas IL‐1β and IL‐1Ra were expressed only in inflammatory cells. Expression of the two IL‐1 receptors and their ligands was significantly higher in patients than in controls. IL‐1 receptor expression on muscle fibers was most pronounced in the vicinity of cells expressing IL‐1α and IL‐1β.ConclusionThe increased expression of IL‐1 receptor and the colocalization with reciprocal ligands in patients with myositis but not in healthy controls support the hypothesis of a crucial role of IL‐1 in the pathogenesis of polymyositis and dermatomyositis.

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Key Biomarkers

IL-1raIL-1RIIL-1RIIIL-1αIL-1β