title: Association between lack of angiogenic response in muscle tissue and high expression of angiostatic ELR-negative CXC chemokines in patients with juvenile dermatomyositis: possible link to vasculopathy.
abstract: OBJECTIVE
  To investigate the relationship between the vasculopathy of juvenile dermatomyositis (juvenile DM) and the balance between the angiostatic ELR- and angiogenic ELR+ CXC chemokines in the muscle of patients with the disease.
  
  
  METHODS
  The expression of 3 ELR- CXC chemokines (interferon-inducible protein 10 [IP-10], monokine induced by interferon-gamma, and interferon-inducible T cell alpha-chemoattractant) and 2 ELR+ CXC chemokines was quantitated in muscle biopsy samples from 7 patients with juvenile DM and 7 healthy children, by real-time polymerase chain reaction. The findings were correlated with various histopathologic features, with particular emphasis on the degree of vasculopathy. Synovial biopsy specimens from patients with juvenile rheumatoid arthritis (JRA) were used for additional comparison.
  
  
  RESULTS
  The angiostatic ELR- chemokines were expressed at high levels, while the angiogenic ELR+ chemokines were barely detectable, in most juvenile DM samples. This contrasted sharply with the findings in both normal muscle biopsy specimens and JRA synovial tissue specimens. The expression of the ELR- chemokines in juvenile DM samples correlated with the intensity of mononuclear cell infiltration. Furthermore, the juvenile DM samples with the highest degree of capillary loss had the highest levels of ELR- CXC chemokines. The presence of IP-10 in juvenile DM muscle specimens was confirmed by immunohistochemistry analysis. In addition, immunohistochemical staining of muscle tissue revealed that CXCR3, a receptor utilized by ELR- CXC chemokines, was expressed in vascular endothelial cells.
  
  
  CONCLUSIONS
  Increased expression of the interferon-induced angiostatic ELR- CXC chemokines is a feature of juvenile DM that parallels the degree of vasculopathy in patients with the disease. Collectively, these findings are consistent with a model in which a subset of inflammatory cells secrete angiostatic ligands, which then contribute to a local atrophying effect on the muscle's vasculature via a receptor-mediated process.
authors.affiliation: Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229, USA.
authors.forename: Ndate
authors.initials: N
authors.lastname: Fall
authors.forename: Kevin E
authors.initials: KE
authors.lastname: Bove
authors.forename: Keith
authors.initials: K
authors.lastname: Stringer
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Lovell
authors.forename: Hermine I
authors.initials: HI
authors.lastname: Brunner
authors.forename: Jennifer
authors.initials: J
authors.lastname: Weiss
authors.forename: Gloria C
authors.initials: GC
authors.lastname: Higgins
authors.forename: Susanne L
authors.initials: SL
authors.lastname: Bowyer
authors.forename: T Brent
authors.initials: TB
authors.lastname: Graham
authors.forename: Sherry
authors.initials: S
authors.lastname: Thornton
authors.forename: Alexei A
authors.initials: AA
authors.lastname: Grom
mesh_terms: D001706:Biopsy; D054357:Chemokine CXCL10; D054371:Chemokine CXCL11; D054370:Chemokine CXCL9; D019743:Chemokines, CXC / Q000235:genetics* / Q000276:immunology; D002648:Child; D003882:Dermatomyositis / Q000276:immunology / Q000473:pathology*; D004730:Endothelium, Vascular / Q000276:immunology / Q000473:pathology; D015870:Gene Expression / Q000276:immunology; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics* / Q000276:immunology; D018482:Muscle, Skeletal / Q000098:blood supply / Q000276:immunology / Q000473:pathology; D009133:Muscular Atrophy / Q000276:immunology / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000276:immunology / Q000473:pathology; D016491:Peripheral Vascular Diseases / Q000276:immunology / Q000473:pathology*
chemical_list: C515202:CXCL11 protein, human; C080810:CXCL9 protein, human; D054357:Chemokine CXCL10; D054371:Chemokine CXCL11; D054370:Chemokine CXCL9; D019743:Chemokines, CXC; D036341:Intercellular Signaling Peptides and Proteins