Department of Neurology, Martin Luther University Halle-Wittenberg, Ernst-Grube-Str. 40, 06120, Halle (Saale), Germany.
Department of Orthopaedic Surgery, Martin Luther University Halle-Wittenberg, Halle (Saale), Germany.
Mol Biol Rep. 2019 Aug;46(4):4085-4094. doi: 10.1007/s11033-019-04858-9. Epub 2019 May 13.
The aetiology of inflammatory myopathies is not clearly known. A predominance of activated Cd8+ T lymphocytes in inflammatory infiltrates has already been detected. Superantigens activate lymphocytes in an oligoclonal manner. In the present investigation, we investigated local effects after injection of the superantigen (Sag) Staphylococcus enterotoxin A (SEA) in the quadriceps femoris muscle of Lewis rats. Histopathology and gene expression profiling was performed after injection of SEA or saline (control group) after one, three and 10 days. Histology revealed focal myositis predominated by Cd8+ T lymphocytes with a perimysial, endomysial and perivascular distribution, peaking 3 days after SEA injection. Using DNA microarray analysis (Affymetrix Rat Genome 230 2.0) genes that were differentially over-expressed at least 15 times at days one, three or ten after SEA injection were further analysed. One day after SEA injection over-expressed genes were related to the immune response (e.g. Fcnb, CD8a) but also to cell proliferation, differentiation and migration (e.g. Mpp2). Three days after SEA injection, differentially overexpressed genes were mainly related to the immune reaction with a clear signature for a Cd8+ T lymphocyte response (e.g. Cd3d, Cd8, Prf1, Gzmb). Ten days after SEA injection, the differentially overexpressed genes were again associated with the immune reaction (e.g. Cd3d, Il2) but also with regenerative processes and wound healing (e.g. Tgfa, Tpm1, Ripply1). The inflammatory response induced by SEA in Lewis rats shares histological and molecular similarities to polymyositis in humans. Therefore, SEA induced myositis can be taken as a new and apt model for polymyositis.
炎性肌病的病因尚不清楚。已经检测到炎症浸润中激活的 CD8+T 淋巴细胞占优势。超抗原以寡克隆方式激活淋巴细胞。在本研究中，我们研究了超抗原（Sag）金黄色葡萄球菌肠毒素 A（SEA）注射到 Lewis 大鼠股四头肌后局部的影响。SEA 或生理盐水（对照组）注射后 1、3 和 10 天进行组织病理学和基因表达谱分析。组织学显示，以 CD8+T 淋巴细胞为主的局灶性肌炎，伴肌周、肌内膜和血管周围分布，SEA 注射后 3 天达到高峰。使用 DNA 微阵列分析（Affymetrix Rat Genome 230 2.0），进一步分析了 SEA 注射后至少 15 倍差异过表达的基因。SEA 注射后 1 天，过表达的基因与免疫反应有关（如 Fcnb、CD8a），但也与细胞增殖、分化和迁移有关（如 Mpp2）。SEA 注射后 3 天，差异过表达的基因主要与免疫反应有关，有明显的 CD8+T 淋巴细胞反应特征（如 CD3d、CD8、Prf1、Gzmb）。SEA 注射后 10 天，差异过表达的基因再次与免疫反应有关（如 CD3d、Il2），但也与再生过程和伤口愈合有关（如 Tgfa、Tpm1、Ripply1）。SEA 在 Lewis 大鼠中诱导的肌炎在组织学和分子上与人类多发性肌炎相似。因此，SEA 诱导的肌炎可以作为一种新的、合适的多发性肌炎模型。
