Down-regulation of the aberrant expression of the inflammation mediator high mobility group box chromosomal protein 1 in muscle tissue of patients with polymyositis and dermatomyositis treated with corticosteroids.
OBJECTIVE
High mobility group box chromosomal protein 1 (HMGB-1) is an endogenous nuclear protein that can be translocated to the cytoplasm and then released extracellularly. It can induce tumor necrosis factor and interleukin-1 production in myeloid cells. Increased expression of these 2 cytokines has been observed in muscle tissue of patients with polymyositis (PM) and dermatomyositis (DM). The present study was therefore undertaken to investigate how HMGB-1 is expressed in muscle tissue of patients with myositis and, if so, whether such expression is modulated by prednisolone therapy.


METHODS
Muscle biopsy specimens from 5 patients with PM and 4 patients with DM, obtained before and 3-6 months after initiation of prednisolone therapy, were assessed by conventional microscopic evaluation and computerized image analysis, and HMGB-1 expression was investigated by immunohistochemical staining. Muscle biopsy specimens from 7 healthy controls were also studied.


RESULTS
Cytoplasmic HMGB-1 expression was detected in infiltrating rounded mononuclear cells, vascular endothelial cells, and muscle fibers of PM and DM patients. Extracellular staining surrounding the inflammatory cells was also observed. After treatment with high-dose prednisolone, cytoplasmic and extracellular HMGB-1 expression was significantly reduced, coinciding mainly with a decreased number of infiltrating inflammatory cells. Cytoplasmic HMGB-1 expression was still evident in endothelial cells and muscle fibers. No HMGB-1 expression was observed in muscle tissue from healthy controls.


CONCLUSIONS
The cytoplasmic and extracellular distribution of HMGB-1 in muscle tissue may indicate an important role of this proinflammatory molecule in the pathogenesis of PM and DM. Furthermore, our findings indicate that systemically administered high-dose corticosteroids selectively down-regulate aberrant expression of HMGB-1 in mononuclear inflammatory cells in vivo.
Ulfgren
Ann-Kristin
AK
Rheumatology Research Unit, CMM L8:04, Karolinska Hospital, Karolinska Institutet, 171-76 Stockholm, Sweden. Ann-Kristin.Ulfgren@cmm.ki.se
Grundtman
Cecilia
C
Borg
Kristian
K
Alexanderson
Helene
H
Andersson
Ulf
U
Harris
Helena Erlandsson
HE
Lundberg
Ingrid E
IE
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001706:Biopsy; D003882:Dermatomyositis / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism*; D015536:Down-Regulation / Q000187:drug effects / Q000276:immunology; D042783:Endothelial Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D005260:Female; D005938:Glucocorticoids / Q000627:therapeutic use*; D024243:HMGB1 Protein / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D018836:Inflammation Mediators / Q000276:immunology / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D018485:Muscle Fibers, Skeletal / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D018482:Muscle, Skeletal / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000097:blood; D011239:Prednisolone / Q000627:therapeutic use*; D020127:Recovery of Function / Q000187:drug effects
D005938:Glucocorticoids; D024243:HMGB1 Protein; D018836:Inflammation Mediators; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D011239:Prednisolone