title: Toll-like receptors promote inflammation in idiopathic inflammatory myopathies.
abstract: The roles of Toll-like receptors (TLRs) and their myeloid differentiation response gene 88 (MyD88)-dependent and MyD88-independent signaling cascade particularly with regard to the pathogenesis and regulation of immune responses in idiopathic inflammatory myopathies are unclear. We investigated these pathways in muscle biopsies from 5 cases each of polymyositis, inclusion body myositis, dermatomyositis, vasculitis-associated interstitial myositis, and noninflammatory neurogenic atrophy. Toll-like receptor 2, TLR4, TLR9, and MyD88 mRNA transcripts and protein expression were increased in all subtypes of idiopathic inflammatory myopathies. Upregulation of MyD88 was associated with increased mRNA levels of interferon-γ, interleukin 12p40, and interleukin 17, suggesting NF-κB activation via the MyD88-dependent pathway in early stages. The costimulatory molecules CD80 and CD86 were expressed on inflammatory infiltrates in idiopathic inflammatory myopathies and may additionally contribute to activation of the MyD88-independent pathway, leading to nuclear factor-κB activation in late stages. Our data suggest that nuclear factor-κB activation via both the MyD88-dependent and the MyD88-independent pathways contributes to the proinflammatory milieu in idiopathic inflammatory myopathies.
authors.affiliation: Department of Neuropathology, University of Cologne, Cologne, Germany. anna.brunn@uni-koeln.de
authors.forename: Anna
authors.initials: A
authors.lastname: Brunn
authors.forename: Katja
authors.initials: K
authors.lastname: Zornbach
authors.forename: Volkmar H
authors.initials: VH
authors.lastname: Hans
authors.forename: Walter F
authors.initials: WF
authors.lastname: Haupt
authors.forename: Martina
authors.initials: M
authors.lastname: Deckert
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008875:Middle Aged; D009220:Myositis / Q000378:metabolism* / Q000473:pathology*; D012333:RNA, Messenger / Q000502:physiology; D051195:Toll-Like Receptor 2 / Q000502:physiology*; D051197:Toll-Like Receptor 4 / Q000502:physiology*; D051217:Toll-Like Receptor 9 / Q000502:physiology*; D051193:Toll-Like Receptors / Q000235:genetics / Q000502:physiology*; D015854:Up-Regulation / Q000235:genetics
chemical_list: D012333:RNA, Messenger; C495342:TLR2 protein, human; C495345:TLR4 protein, human; C495371:TLR9 protein, human; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051217:Toll-Like Receptor 9; D051193:Toll-Like Receptors