title: Distribution of the NF-kappaB complex in the inflammatory exudates characterizing the idiopathic inflammatory myopathies.
abstract: The transcription factor nuclear factor-kappaB (NF-kappaB) is a ubiquitously expressed protein family that is considered crucial in autoimmunity. We describe NF-kappaB p50 and p65, and the inhibitor I-kappaB alpha in the inflammatory exudates characteristic for the different idiopathic inflammatory myopathies (IIM), that is, endomysial CD8(+) cytotoxic T cells invading non-necrotic fibers in polymyositis (PM) and sporadic inclusion body myositis (sIBM), and the perimysial/perivascular CD20(+) B cells and CD4(+) T cells in dermatomyositis (DM). We also analyzed other inflammatory cells in the vicinity of active inflammation sites. Strikingly, actively invading CD4(+) cells in PM and sIBM contained both p65 and p50, whereas I-kappaB alpha was absent. This could point to a high activation state in which these cells are capable of expressing a variety of inflammatory mediators, contributing to the degradation of non-necrotic fibers. Secondly, CD68(+) macrophages in the infiltrates in all three IIM subtypes showed strong nuclear p50 and I-kappaB alpha staining. This may point to a role for p50 in counteracting inflammation, a reaction that could be enhanced by an upregulation of I-kappaB alpha as we observed with immunofluorescence. These results shed further light on the immunopathology of PM, sIBM and DM. CD4(+) and CD68(+) mononuclear cells may play a more prominent role than previously assumed.
authors.affiliation: Department of Neurology, Ghent University Hospital, Belgium.
authors.forename: Kim K
authors.initials: KK
authors.lastname: Creus
authors.forename: Boel
authors.initials: B
authors.lastname: De Paepe
authors.forename: Bart F
authors.initials: BF
authors.lastname: Werbrouck
authors.forename: Veerle
authors.initials: V
authors.lastname: Vervaet
authors.forename: Joachim
authors.initials: J
authors.lastname: Weis
authors.forename: Jan L
authors.initials: JL
authors.lastname: De Bleecker
mesh_terms: D015703:Antigens, CD / Q000378:metabolism; D018951:Antigens, CD20 / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D001402:B-Lymphocytes / Q000378:metabolism / Q000473:pathology; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism / Q000473:pathology; D003882:Dermatomyositis / Q000378:metabolism / Q000473:pathology; D005122:Exudates and Transudates / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism*; D007150:Immunohistochemistry; D007249:Inflammation / Q000378:metabolism / Q000473:pathology; D008264:Macrophages / Q000378:metabolism / Q000473:pathology; D009220:Myositis / Q000378:metabolism* / Q000473:pathology; D018979:Myositis, Inclusion Body / Q000378:metabolism / Q000473:pathology; D000072000:NF-KappaB Inhibitor alpha; D052002:NF-kappa B p50 Subunit / Q000378:metabolism*; D051996:Transcription Factor RelA / Q000378:metabolism*; D000097382:CD68 Molecule
chemical_list: D015703:Antigens, CD; D018951:Antigens, CD20; D015214:Antigens, Differentiation, Myelomonocytic; D020672:I-kappa B Proteins; D000072000:NF-KappaB Inhibitor alpha; D052002:NF-kappa B p50 Subunit; D051996:Transcription Factor RelA; C067980:CD68 antigen, human; D000097382:CD68 Molecule; C000606204:NFKBIA protein, human