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Effects of HMGB1 on in vitro responses of isolated muscle fibers and functional aspects in skeletal muscles of idiopathic inflammatory myopathies
Author(s) -
Grundtman Cecilia,
Bruton Joseph,
Yamada Takashi,
Östberg Therese,
Pisetsky David S.,
Harris Helena Erlandsson,
Andersson Ulf,
Lundberg Ingrid E.,
Westerblad Håkan
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.09-144782
Subject(s) - skeletal muscle , hmgb1 , muscle weakness , major histocompatibility complex , myocyte , inflammation , mhc class i , chemistry , medicine , endocrinology , biology , immunology , immune system
Idiopathic inflammatory myopathies (IIMs) are heterogeneous rheumatic disorders of unknown cause characterized by muscle weakness, inflammatory cell infiltrates, and major histocompatibility complex (MHC) class I expression on muscle fibers. The nonhistone nuclear protein alarmin high‐mobility group box 1 protein (HMGB1) has been detected extranuclearly in muscle biopsies from patients with IIMs. We hypothesize that HMGB1 has a central role in the cause of muscle weakness, particularly in the early phases of IIMs. Experiments were performed on skeletal muscle fibers isolated from adult mice, which were exposed to recombinant interferon (IFN)‐γ or HMGB1. The myoplasmic free [Ca 2+ ] was measured. Stimulation with IFN‐γ resulted in increased HMGB1 expression in muscle nuclei and the myoplasm. Exposure to HMGB1 induced a reversible up‐regulation of MHC class I in the muscle fibers. However, HMGB1 exposure caused an irreversible decrease in Ca 2+ release from the sarcoplasmic reticulum during fatigue, induced by repeated tetanic contractions. HMGB1 and MHC class I were frequently colocalized in the myoplasm of muscle fibers in muscle biopsies from patients with early IIMs. However, HMGB1‐expressing fibers outnumbered fibers expressing MHC class I. Our data indicate that HMGB1 could be an early inducer of skeletal muscle dysfunction in IIMs.—Grundtman, C., Bruton, J., Yamada, T., Östberg, T., Pisetsky, D. S., Harris, H. E., Andersson, U., Lundberg, I. E., Westerblad, H. Effects of HMGB1 on in vitro responses of isolated muscle fibers and functional aspects in skeletal muscles of idiopathic inflammatory myopathies. FASEB J . 24, 570–578 (2010). www.fasebj.org