Expression of toll-like receptors by human muscle cells in vitro and in vivo: TLR3 is highly expressed in inflammatory and HIV myopathies, mediates IL-8 release and up-regulation of NKG2D-ligands

Bettina Schreiner, Joachim Voss, Jörg Wischhusen, Yvonne Dombrowski, Alexander Steinle, Hanns Lochmüller, Marinos Dalakas, Arthur Melms, Heinz Wiendl

Research output: Contribution to journalArticle

66 Citations (Scopus)

Abstract

The particular microenvironment of the skeletal muscle can be the site of complex immune reactions. Toll-like receptors (TLRs) mediate inflammatory stimuli from pathogens and endogenous danger signals and link the innate and adaptive immune system. We investigated innate immune responses in human muscle. Analyzing TLR1-9 mRNA in cultured myoblasts and rhabdomyosarcoma cells, we found constitutive expression of TLR3. The TLR3 ligand Poly (I:C), a synthetic analog of dsRNA, and IFN-gamma increased TLR3 levels. TLR3 was mainly localized intracellularly and regulated at the protein level. Poly (I:C) challenge 1) activated nuclear factor-kappaB (NF-kappaB), 2) increased IL-8 release, and 3) up-regulated NKG2D ligands and NK-cell-mediated lysis of muscle cells. We examined muscle biopsy specimens of 6 HIV patients with inclusion body myositis/polymyositis (IBM/PM), 7 cases of sporadic IBM and 9 nonmyopathic controls for TLR3 expression. TLR3 mRNA levels were elevated in biopsy specimens from patients with IBM and HIV-myopathies. Muscle fibers in inflammatory myopathies expressed TLR3 in close proximity of infiltrating mononuclear cells. Taken together, our study suggests an important role of TLR3 in the immunobiology of muscle, and has substantial implications for the understanding of the pathogenesis of inflammatory myopathies or therapeutic interventions like vaccinations or gene transfer.
Original languageEnglish
Pages (from-to)118-20
Number of pages3
JournalThe FASEB Journal
Volume20
Issue number1
DOIs
Publication statusPublished - Jan 2006

Keywords

  • Cell Line
  • Gene Expression Regulation
  • HIV Infections
  • Humans
  • Inflammation
  • Interferon-gamma
  • Interleukin-8
  • Ligands
  • Muscle, Skeletal
  • Muscular Diseases
  • NF-kappa B
  • NK Cell Lectin-Like Receptor Subfamily K
  • RNA, Messenger
  • Receptors, Immunologic
  • Receptors, Natural Killer Cell
  • Signal Transduction
  • Toll-Like Receptor 3

Fingerprint Dive into the research topics of 'Expression of toll-like receptors by human muscle cells in vitro and in vivo: TLR3 is highly expressed in inflammatory and HIV myopathies, mediates IL-8 release and up-regulation of NKG2D-ligands'. Together they form a unique fingerprint.

  • Cite this