Upregulation of chemokines and their receptors in duchenne muscular dystrophy: potential for attenuation of myofiber necrosis
Upregulation of chemokines and their receptors in duchenne muscular dystrophy: potential for attenuation of myofiber necrosis
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DOI：
10.1002/mus.23481
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发表时间：
2012-12-01
期刊：
影响因子：
3.4
通讯作者：
De Bleecker, Jan L.
中科院分区：
文献类型：
--
作者：
De Paepe, Boel;Creus, Kim K.;De Bleecker, Jan L.
前言：在Duchenne肌营养不良症(DMD)中，免疫细胞对骨骼肌的渗透加重了疾病，但这些炎症反应背后的确切机制仍不清楚。趋化细胞因子，或称趋化因子，被认为是炎性细胞向组织募集的基本分子。方法：应用免疫组织化学、免疫荧光和原位杂交技术检测9例DMD肌肉组织中趋化因子及其受体的表达。结果：DMD肌纤维中存在CXCL1、CXCL2、CXCL3、CXCL8和CXCL11等正常肌纤维中缺失的CXCL1、CXCL2、CXCL3、CXCL8和CXCL11。DMD患者血管内皮细胞上CXCL11、CXCL12及配体受体偶联CCL2CCR2表达上调。CD68+巨噬细胞高水平表达CXCL8、CCL2和CCL5。结论：我们的数据表明CXCR1/2/4配体在管理肌肉纤维损伤控制和组织再生方面可能起到有益的作用。细胞毒性巨噬细胞上调内皮细胞趋化因子受体和CXCL8、CCL2和CCL5的表达可能调节肌纤维坏死。肌肉神经46：917-925,2012
Introduction: In Duchenne muscular dystrophy (DMD), the infiltration of skeletal muscle by immune cells aggravates disease, yet the precise mechanisms behind these inflammatory responses remain poorly understood. Chemotactic cytokines, or chemokines, are considered essential recruiters of inflammatory cells to the tissues. Methods: We assayed chemokine and chemokine receptor expression in DMD muscle biopsies (n = 9, average age 7 years) using immunohistochemistry, immunofluorescence, and in situ hybridization. Results: CXCL1, CXCL2, CXCL3, CXCL8, and CXCL11, absent from normal muscle fibers, were induced in DMD myofibers. CXCL11, CXCL12, and the ligandreceptor couple CCL2CCR2 were upregulated on the blood vessel endothelium of DMD patients. CD68+ macrophages expressed high levels of CXCL8, CCL2, and CCL5. Conclusions: Our data suggest a possible beneficial role for CXCR1/2/4 ligands in managing muscle fiber damage control and tissue regeneration. Upregulation of endothelial chemokine receptors and CXCL8, CCL2, and CCL5 expression by cytotoxic macrophages may regulate myofiber necrosis. Muscle Nerve 46: 917-925, 2012