Laboratory for Myopathology, Department of Neurology and Neuromuscular Reference Center, Ghent University Hospital, Belgium.
Neurosci Lett. 2013 Feb 22;535:18-23. doi: 10.1016/j.neulet.2012.11.064. Epub 2013 Jan 4.
Although polymyositis (PM) and sporadic inclusion body myositis (IBM) represent distinct disease entities, both are associated with the autoimmune destruction of muscle fibers. We investigated the pro-inflammatory mechanisms around the nonnecrotic invaded muscle fiber, comparing between PM and IBM. The expression and distribution of chemokines, inducible NO synthase (iNOS), and heat shock proteins (HSP) was studied in detail, using immunofluorescence, and western blotting. Important upregulation of the cytotoxic tandem HSP90/iNOS and the chemokines: IFNγ inducible protein of 10kd, stromal cell-derived factor and monocyte chemoattractant protein 1, were observed in the actively invading inflammatory cells. From our results, we propose a model in which the joint action of chemokines and cytotoxic factors in cytotoxic T-cells, macrophages and myeloid dendritic cells invading the myofiber, ultimately leads to its demise. The processes described seem to be universal to PM and IBM alike. Our observations further consolidate the important autoimmune component of IBM, a feature still under debate within the scientific community.
虽然多发性肌炎（PM）和散发性包涵体肌炎（IBM）代表不同的疾病实体，但它们都与肌肉纤维的自身免疫性破坏有关。我们研究了非坏死性侵犯肌纤维周围的促炎机制，比较了 PM 和 IBM。使用免疫荧光和 Western blot 详细研究了趋化因子、诱导型一氧化氮合酶（iNOS）和热休克蛋白（HSP）的表达和分布。在活跃浸润的炎性细胞中观察到细胞毒性串联 HSP90/iNOS 和趋化因子 IFNγ 诱导的 10kd 蛋白、基质细胞衍生因子和单核细胞趋化蛋白 1 的重要上调。根据我们的结果，我们提出了一个模型，即浸润肌纤维的细胞毒性 T 细胞、巨噬细胞和髓样树突状细胞中的趋化因子和细胞毒性因子的共同作用，最终导致肌纤维的死亡。所描述的过程似乎对 PM 和 IBM 都是普遍存在的。我们的观察结果进一步巩固了 IBM 中的重要自身免疫成分，这一特征在科学界仍存在争议。
