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

✍ Scribed by Ann-Kristin Ulfgren; Cecilia Grundtman; Kristian Borg; Helene Alexanderson; Ulf Andersson; Helena Erlandsson Harris; Ingrid E. Lundberg

• Publisher: John Wiley and Sons
• Year: 2004
• Tongue: English
• Weight: 318 KB
• Volume: 50
• Category: Article
• ISSN: 0004-3591
• DOI: 10.1002/art.20220

✦ Synopsis

Abstract

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.

Conclusion

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.