De Bleecker J L, Meire V I, Declercq W, Van Aken E H
Neurology Department, University Hospital, Gent, Belgium.
Neuromuscul Disord. 1999 Jun;9(4):239-46. doi: 10.1016/s0960-8966(98)00126-6.
Adhesion molecule upregulation occurs in inflammatory myopathies, and is one of the myriad functions of tumor necrosis factor-alpha (TNF-alpha). TNF-alpha acts via two different receptors of 55 (TNF-R55) and 75 kD (TNF-R75). We immunolocalized TNF-alpha and its receptors in polymyositis, inclusion body myositis and dermatomyositis. In each myopathy, TNF-alpha was detected in macrophages, in myonuclei in regenerating muscle fibers, and freely dispersed in endomysial or perimysial connective tissue. Many endothelial cells in dermatomyositis expressed TNF-alpha. TNF-R55 was strongly expressed on myonuclei of regenerating muscle fibers. TNF-R75 was increased on endothelial cells in the midst of inflammatory infiltrates in each myopathy, and on perifascicular and perimysial endothelia, remote from inflammatory foci in dermatomyositis. Possible TNF-alpha-mediated effects include: increased transendothelial cell trafficking, activation of T/B cells and macrophages, induction of MHC-I gene products, and focal muscle fiber atrophy. In dermatomyositis, the upregulated TNF-R75, via its consensus elements for transcription factors, may be involved in endothelial cell degeneration. Strong TNF-R55 expression on regenerating myonuclei is consistent with a role of TNF-alpha and TNF-R55 in muscle regeneration.
黏附分子上调发生在炎性肌病中，是肿瘤坏死因子-α（TNF-α）众多功能之一。TNF-α通过55kD（TNF-R55）和75kD（TNF-R75）两种不同受体发挥作用。我们对多肌炎、包涵体肌炎和皮肌炎中的TNF-α及其受体进行了免疫定位。在每种肌病中，巨噬细胞、再生肌纤维中的肌核以及散在于肌内膜或肌束膜结缔组织中的TNF-α均可被检测到。皮肌炎中的许多内皮细胞表达TNF-α。TNF-R55在再生肌纤维的肌核上强烈表达。TNF-R75在每种肌病炎症浸润部位的内皮细胞上增加，在皮肌炎远离炎症灶的束周和肌束膜内皮细胞上也增加。TNF-α可能介导的效应包括：增加跨内皮细胞运输、激活T/B细胞和巨噬细胞、诱导MHC-I基因产物以及局部肌纤维萎缩。在皮肌炎中，上调的TNF-R75通过其转录因子共有元件，可能参与内皮细胞变性。再生肌核上强烈的TNF-R55表达与TNF-α和TNF-R55在肌肉再生中的作用一致。
