Persistent over-expression of specific CC class chemokines correlates with macrophage and T-cell recruitment in mdx skeletal muscle.
Prior studies and the efficacy of immunotherapies provide evidence that inflammation is mechanistic in pathogenesis of Duchenne muscular dystrophy. To identify putative pro-inflammatory mechanisms, we evaluated chemokine gene/protein expression patterns in skeletal muscle of mdx mice. By DNA microarray, reverse transcription-polymerase chain reaction, quantitative polymerase chain reaction, and immunoblotting, convergent evidence established the induction of six distinct CC class chemokine ligands in adult MDX: CCL2/MCP-1, CCL5/RANTES, CCL6/mu C10, CCL7/MCP-3, CCL8/MCP-2, and CCL9/MIP-1gamma. CCL receptors, CCR2, CCR1, and CCR5, also showed increased expression in mdx muscle. CCL2 and CCL6 were localized to both monocular cells and muscle fibers, suggesting that dystrophic muscle may contribute toward chemotaxis. Temporal patterns of CCL2 and CCL6 showed early induction and maintained expression in mdx limb muscle. These data raise the possibility that chemokine signaling pathways coordinate a spatially and temporally discrete immune response that may contribute toward muscular dystrophy. The chemokine pro-inflammatory pathways described here in mdx may represent new targets for treatment of Duchenne muscular dystrophy.
Porter
John D
JD
Department of Ophthalmology, Case Western Reserve University and The Research Institute of University Hospitals of Cleveland, Cleveland, OH 44106-5068, USA. jdp7@po.cwru.edu
Guo
Wei
W
Merriam
Anita P
AP
Khanna
Sangeeta
S
Cheng
Georgiana
G
Zhou
Xiaohua
X
Andrade
Francisco H
FH
Richmonds
Chellah
C
Kaminski
Henry J
HJ
D000818:Animals; D000831:Animals, Newborn; D015153:Blotting, Western; D018946:Chemokine CCL5 / Q000378:metabolism; D019742:Chemokines, CC / Q000145:classification / Q000378:metabolism*; D016000:Cluster Analysis; D017931:DNA Primers; D004195:Disease Models, Animal; D015870:Gene Expression; D006614:Hindlimb / Q000378:metabolism; D007150:Immunohistochemistry; D008024:Ligands; D008264:Macrophages / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018101:Mice, Inbred mdx; D018945:Monocyte Chemoattractant Proteins / Q000145:classification / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism / Q000502:physiology*; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D012333:RNA, Messenger / Q000032:analysis; D019707:Receptors, Chemokine / Q000145:classification / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000502:physiology*
D018946:Chemokine CCL5; D019742:Chemokines, CC; D017931:DNA Primers; D008024:Ligands; D018945:Monocyte Chemoattractant Proteins; D012333:RNA, Messenger; D019707:Receptors, Chemokine