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Expression and distribution of the nitric oxide synthases in idiopathic inflammatory myopathies

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Abstract

Different immune effector mechanisms have been characterised in the idiopathic inflammatory myopathies (IIM): in polymyositis (PM) and sporadic inclusion body myositis (sIBM), T-cell-mediated cytotoxicity targets nonnecrotic muscle fibres, whereas in dermatomyositis (DM) the complement-mediated immune response is directed against the microvasculature. As nitric oxide (NO) has an important function in cell signalling and in the cytotoxicity displayed by activated macrophages, it is potentially involved in the immunopathogenesis of IIM. Using immunohistochemical, in situ hybridisation and Western blotting techniques, we visualised the three isoforms of NO synthase (NOS) in muscle tissues from normal controls and from patients diagnosed with IIM. The levels of both constitutive isoforms of NOS (endothelial, i.e., eNOS, and neuronal, i.e., nNOS) were unchanged in IIM as compared with normal muscle. Both protein and mRNA of the inducible form (iNOS) were detected in half of the control biopsies. Constant and increased iNOS protein expression was found in endomysial infiltrates of PM and sIBM, whereas perimysial inflammatory cells in DM were largely negative. We developed a quantitative Western blotting protocol which confirmed the constitutive nature of nNOS and eNOS and the significant induction of iNOS in PM. Our results appoint iNOS with a dual function: a limited and transient role in normal muscle physiology and an active cytotoxic role in PM and sIBM.

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Acknowledgements

This work was supported by grants from the Ghent Flemish University Research Fund for Bilateral Collaboration, the Flemish Fund for Scientific Research, the Belgian Association against Neuromuscular Disorders (ABMM) and “KidAuQuai”.

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Authors and Affiliations

  1. Department of Neurology, Ghent University Hospital, De Pintelaan 185, 9000, Ghent, Belgium

    Boel De Paepe & Jan L. De Bleecker

  2. Institute of Biochemistry, University of Szeged, Szeged, Hungary

    Gabor Z. Racz

  3. Institut für Neuropathologie, Universitätsklinikum der Rheinisch-Westphälischen Technische Hochschule Aachen, Aachen, Germany

    J. Michael Schröder

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  1. Boel De Paepe
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  2. Gabor Z. Racz
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  3. J. Michael Schröder
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  4. Jan L. De Bleecker
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Correspondence to Jan L. De Bleecker.

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De Paepe, B., Racz, G.Z., Schröder, J.M. et al. Expression and distribution of the nitric oxide synthases in idiopathic inflammatory myopathies. Acta Neuropathol 108, 37–42 (2004). https://doi.org/10.1007/s00401-004-0859-6

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  • DOI: https://doi.org/10.1007/s00401-004-0859-6

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