Cathepsins are upregulated by IFN-γ/STAT1 in human muscle culture: A possible active factor in dermatomyositis

Eduard Gallardo, Irene De Andrés, Isabel Illa

Research output: Contribution to journalArticleResearchpeer-review

34 Citations (Scopus)

Abstract

The aim of this work was to study which genes upregulated by the IFN-γ/STAT1 system in human muscle might be involved in the process of muscle fiber atrophy in dermatomyositis (DM). These proteins included proteases (cathepsins B and L, calpain), proteins implicated in apoptosis and cell cycle (Bcl-x(1), Fas, p21), structural proteins (β-actin, utrophin, desmin), and other proteins whose expression is known to be modified by IFN-γ (neural cell adhesion molecule (N-CAM), major histocompatibility complex-I (MHC-I)). We performed immunocytochemistry, Western blot, and semiquantitative reverse transcriptase-polymerase chain reaction using human muscle cultures. We found upregulation of cathepsins B and L, bcl-x(1) and p21 while N-CAM, calpain, utrophin, desmin, β-actin and Fas remained at basal levels. Immunohistochemistry on frozen sections from biopsies of patients with different muscle diseases showed upregulation of cathepsin L and calpain in perifascicular muscle fibers in DM. In view of these results, the increased expression of cathepsins L and B after IFN-γ stimulation in muscle cultures and its inhibition using fludarabine, a STAT1 blocker, further support our previous studies and suggest that the increased expression of cathepsins detected in perifascicular muscle fibers in DM is mediated by IFN-γ/STAT1 and contributes to their atrophy.
Original languageEnglish
Pages (from-to)847-855
JournalJournal of Neuropathology and Experimental Neurology
Volume60
Issue number9
DOIs
Publication statusPublished - 1 Jan 2001

Keywords

  • Cathepsins
  • Dermatomyositis
  • Fludarabine
  • IFN-γ/STAT1
  • Inflammatory myopathy

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