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  • Title: Upregulation of chemokines and their receptors in Duchenne muscular dystrophy: potential for attenuation of myofiber necrosis.
    Author: De Paepe B, Creus KK, Martin JJ, De Bleecker JL.
    Journal: Muscle Nerve; 2012 Dec; 46(6):917-25. PubMed ID: 23225384.
    Abstract:
    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 ligand-receptor couple CCL2-CCR2 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.
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