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

Arthritis Rheum. 2007 Feb;56(2):674-87. doi: 10.1002/art.22388.

Abstract

Objective: Interleukin-1 (IL-1) acts via its receptors to induce gene expression that mediates protein synthesis involved in inflammation. Increased expression of IL-1alpha and IL-1beta 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.

Methods: Muscle 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-1alpha, IL-1beta, 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.

Results: In 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-1alpha was expressed in endothelial cells and inflammatory cells, whereas IL-1beta 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-1alpha and IL-1beta.

Conclusion: The 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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Case-Control Studies
  • Cell Nucleus / metabolism*
  • Cell Nucleus / ultrastructure
  • Dermatomyositis / genetics
  • Dermatomyositis / metabolism
  • Dermatomyositis / pathology
  • Female
  • Gene Expression Regulation
  • Humans
  • Interleukin 1 Receptor Antagonist Protein / genetics
  • Interleukin 1 Receptor Antagonist Protein / metabolism
  • Interleukin-1alpha / genetics
  • Interleukin-1alpha / metabolism
  • Interleukin-1beta / genetics
  • Interleukin-1beta / metabolism
  • Male
  • Middle Aged
  • Monocytes / metabolism
  • Monocytes / pathology
  • Muscle, Skeletal / metabolism*
  • Muscle, Skeletal / pathology
  • Myositis / genetics
  • Myositis / metabolism*
  • Myositis / pathology
  • Polymyositis / genetics
  • Polymyositis / metabolism
  • Polymyositis / pathology
  • Receptors, Interleukin-1 / genetics
  • Receptors, Interleukin-1 / metabolism*
  • Sarcolemma / metabolism*
  • Sarcolemma / ultrastructure

Substances

  • Interleukin 1 Receptor Antagonist Protein
  • Interleukin-1alpha
  • Interleukin-1beta
  • Receptors, Interleukin-1