title: Upregulation of chemokines and their receptors in Duchenne muscular dystrophy: potential for attenuation of myofiber necrosis.
abstract: BACKGROUND
  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.
authors.affiliation: Laboratory for Myopathology, Department of Neurology and Neuromuscular Reference Center, Ghent University Hospital, De Pintelaan 185, B-9000 Ghent, Belgium. boel.depaepe@ugent.be
authors.forename: Boel
authors.initials: B
authors.lastname: De Paepe
authors.forename: Kim K
authors.initials: KK
authors.lastname: Creus
authors.forename: Jean-Jacques
authors.initials: JJ
authors.lastname: Martin
authors.forename: Jan L
authors.initials: JL
authors.lastname: De Bleecker
mesh_terms: D000328:Adult; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D001402:B-Lymphocytes / Q000378:metabolism / Q000473:pathology; D001808:Blood Vessels / Q000378:metabolism / Q000473:pathology; D018925:Chemokines / Q000235:genetics / Q000378:metabolism*; D002648:Child; D002675:Child, Preschool; D003713:Dendritic Cells / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D008264:Macrophages / Q000378:metabolism / Q000473:pathology; D008297:Male; D018485:Muscle Fibers, Skeletal / Q000473:pathology; D018482:Muscle, Skeletal / Q000473:pathology; D020388:Muscular Dystrophy, Duchenne / Q000378:metabolism* / Q000503:physiopathology*; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D019707:Receptors, Chemokine / Q000235:genetics / Q000378:metabolism*; D013601:T-Lymphocytes / Q000378:metabolism / Q000473:pathology; D015854:Up-Regulation / Q000502:physiology*; D055815:Young Adult; D000097382:CD68 Molecule
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D018925:Chemokines; D052247:Nitric Oxide Synthase Type II; D019707:Receptors, Chemokine; C067980:CD68 antigen, human; D000097382:CD68 Molecule