TY - JOUR
T1 - Expression of IFN-γ-inducible chemokines in inclusion body myositis
AU - Raju, Raghavanpillai
AU - Vasconcelos, Olavo
AU - Granger, Rebekah
AU - Dalakas, Marinos C.
N1 - Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.
PY - 2003/8
Y1 - 2003/8
N2 - Because IFN-γ-inducible chemokines, Mig (CXCL9), IP-10 (CXCL10), I-TAC (CXCL11) and their receptor, CXCR3, are critical molecules in T cell trafficking and generation of effector T cells, we examined their expression in the muscle biopsies of patients with sporadic inclusion body myositis (s-IBM) and disease controls. The functional role of these molecules was also studied by examining the effect and time kinetics of IFN-γ in inducing Mig and IP-10 expression in human myotubes in vitro. We found significantly high levels of Mig and IP-10 mRNA expression in s-IBM muscles compared to controls. IFN-γ upregulated the mRNA expression of Mig and IP-10 by human myotubes in a dose-dependent manner. By double-label immunohistochemistry, Mig was expressed on a subset of CD8+ cells and the areas of the muscle fiber in contact or contiguous to the T cells; CXCR3 was expressed only on a subset of the autoinvasive CD8+ T cells but not the myofibers. IP-10 and I-TAC were not detected by immunocytochemistry. The findings indicate that in s-IBM, IFN-γ is involved in the upregulation and in situ production of proinflammatory chemokines, which, in turn, participate in the recruitment of activated T cells and contribute to the self-sustaining nature of endomysial inflammation. Crown
AB - Because IFN-γ-inducible chemokines, Mig (CXCL9), IP-10 (CXCL10), I-TAC (CXCL11) and their receptor, CXCR3, are critical molecules in T cell trafficking and generation of effector T cells, we examined their expression in the muscle biopsies of patients with sporadic inclusion body myositis (s-IBM) and disease controls. The functional role of these molecules was also studied by examining the effect and time kinetics of IFN-γ in inducing Mig and IP-10 expression in human myotubes in vitro. We found significantly high levels of Mig and IP-10 mRNA expression in s-IBM muscles compared to controls. IFN-γ upregulated the mRNA expression of Mig and IP-10 by human myotubes in a dose-dependent manner. By double-label immunohistochemistry, Mig was expressed on a subset of CD8+ cells and the areas of the muscle fiber in contact or contiguous to the T cells; CXCR3 was expressed only on a subset of the autoinvasive CD8+ T cells but not the myofibers. IP-10 and I-TAC were not detected by immunocytochemistry. The findings indicate that in s-IBM, IFN-γ is involved in the upregulation and in situ production of proinflammatory chemokines, which, in turn, participate in the recruitment of activated T cells and contribute to the self-sustaining nature of endomysial inflammation. Crown
KW - CXCR3
KW - Chemokines
KW - IP-10
KW - Inclusion body myositis
KW - Mig
KW - Myotube
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U2 - 10.1016/S0165-5728(03)00218-2
DO - 10.1016/S0165-5728(03)00218-2
M3 - Article
C2 - 12965263
AN - SCOPUS:0142107309
SN - 0165-5728
VL - 141
SP - 125
EP - 131
JO - Journal of Neuroimmunology
JF - Journal of Neuroimmunology
IS - 1-2
ER -