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


CONCLUSIONS
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.
Grundtman
Cecilia
C
Rheumatology Research Unit, Karolinska University Hospital Solna and Karolinska Institutet, Stockholm, Sweden. cecilia.grundtman@cmm.ki.se
Salomonsson
Stina
S
Dorph
Christina
C
Bruton
Joseph
J
Andersson
Ulf
U
Lundberg
Ingrid E
IE
D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D002467:Cell Nucleus / Q000378:metabolism* / Q000648:ultrastructure; D003882:Dermatomyositis / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein / Q000235:genetics / Q000378:metabolism; D053582:Interleukin-1alpha / Q000235:genetics / Q000378:metabolism; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism / Q000473:pathology; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000473:pathology; D009220:Myositis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D017285:Polymyositis / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D017472:Receptors, Interleukin-1 / Q000235:genetics / Q000378:metabolism*; D012508:Sarcolemma / Q000378:metabolism* / Q000648:ultrastructure
D053590:Interleukin 1 Receptor Antagonist Protein; D053582:Interleukin-1alpha; D053583:Interleukin-1beta; D017472:Receptors, Interleukin-1