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

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 High mobility group box chromosomal protein 1 (HMGB-1; previously termed HMG-1 or amphoterin) is a structural nuclear protein that binds DNA. It is ubiquitously present in the nuclei of all mammalian cells and is highly conserved between species (1). HMGB-1 can be released extracellularly and then has proinflammatory properties (2,3). It has recently been discovered that monocyte/macrophages activated by endotoxin, tumor necrosis factor (TNF), or interleukin-1 (IL-1) secrete HMGB-1 in substantial amounts (4). Furthermore, recent evidence implicates HMGB-1 as an important proinflammatory molecule in several conditions, such as

Vascular endothelial growth factor is highly expressed in muscle tissue of patients with polymyositis and patients with dermatomyositis

“…Group B comprised 10 patients (7 women and 3 men) with recent-onset PM or DM with inflammatory infiltrates in their biopsy specimens and for whom a second biopsy specimen was obtained (according to a predefined protocol) after 3-6 months of high-dose prednisolone treatment. Clinical data on these patients have been described previously (14,28). The median age at diagnosis was 50 years (range 23-80 years).…”

“…Both conventional microscopic evaluation and computerized image analysis were used for the evaluation of VEGF and CD31 expression. The microscope used for the analysis has been described previously (28). All sections were independently assessed by 2 investigators (CG and IEL), with concordant results.…”

A Longitudinal, Integrated, Clinical, Histological and mRNA Profiling Study of Resistance Exercise in Myositis

“…Both subsets have a similar molecular expression profile. The most consistently expressed cytokines in different phases of both polymyositis and dermatomyositis are interleukin (IL)-1 and the alarmin high-mobility group box chromosomal protein (HMGB)-1 (6)(7)(8). These cytokines have been detected in muscle tissue with a higher expression than in healthy individuals in both the early and late chronic phase of the disease, even without detectable inflammatory cell infiltrates.…”

Immune and myodegenerative pathomechanisms in inclusion body myositis

“…RAGE, in association with reactive oxygen species‐ and NF κ B‐dependent pathways and HMGB1 are overexpressed in myositis 308, 309, 310. In IBM muscle, RAGE and HMGB1 colocalize with A β and neurofilament/tau and composite exposure of human muscle cells with IFN γ and IL‐1 β leads to cytoplasmic translocation and subsequent release of HMGB1 into the extracellular space 310.…”