Persistent over-expression of specific CC class chemokines correlates with macrophage and T-cell recruitment in mdx skeletal muscle

John D. Porter; Wei Guo; Anita P. Merriam; Sangeeta Khanna; Georgiana Cheng; Xiaohua Zhou; Francisco H. Andrade; Chellah Richmonds; Henry J. Kaminski

doi:10.1016/s0960-8966(02)00242-0

Persistent over-expression of specific CC class chemokines correlates with macrophage and T-cell recruitment in mdx skeletal muscle

John D. Porter, Wei Guo, Anita P. Merriam, Sangeeta Khanna, Georgiana Cheng, Xiaohua Zhou, Francisco H. Andrade, Chellah Richmonds, Henry J. Kaminski

Physiology

Research output: Contribution to journal › Article › peer-review

78 Scopus citations

Abstract

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-1γ. 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.

Original language	English
Pages (from-to)	223-235
Number of pages	13
Journal	Neuromuscular Disorders
Volume	13
Issue number	3
DOIs	https://doi.org/10.1016/s0960-8966(02)00242-0
State	Published - Mar 2003

Bibliographical note

Funding Information:
We thank Patrick Leahy, Marty Veigl, and the Ireland Cancer Center Gene Expression Array Core Facility for DNA microarray assistance, Denney Hatala for immunocytochemistry, Beth Ann Benetz for assistance with illustrations, Lee Hyson for help with data analysis, and Eric Pearlman, Richard Ransohoff, and Richard Zigmond for helpful discussions. This work was supported by grants from The Research Institute of University Hospitals of Cleveland, Research to Prevent Blindness (Departmental Grant; Senior Scientific Investigator Award to J.D.P.), the Knight Templar Eye Research Foundation (S.K.), the Muscular Dystrophy Association USA (J.D.P.), and NIH Grants R01 EY09834 (J.D.P.), R01 EY12779 (J.D.P.), and P30 EY11373. J.D.P. is also supported by funding from the Carl F. Asseff, M.D. Professorship in Ophthalmology.

Keywords

Chemokine
Chemotaxis
Mdx
Muscular dystrophy

ASJC Scopus subject areas

Pediatrics, Perinatology, and Child Health
Neurology
Clinical Neurology
Genetics(clinical)

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10.1016/s0960-8966(02)00242-0

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title = "Persistent over-expression of specific CC class chemokines correlates with macrophage and T-cell recruitment in mdx skeletal muscle",

abstract = "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-1γ. 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.",

keywords = "Chemokine, Chemotaxis, Mdx, Muscular dystrophy",

author = "Porter, {John D.} and Wei Guo and Merriam, {Anita P.} and Sangeeta Khanna and Georgiana Cheng and Xiaohua Zhou and Andrade, {Francisco H.} and Chellah Richmonds and Kaminski, {Henry J.}",

note = "Funding Information: We thank Patrick Leahy, Marty Veigl, and the Ireland Cancer Center Gene Expression Array Core Facility for DNA microarray assistance, Denney Hatala for immunocytochemistry, Beth Ann Benetz for assistance with illustrations, Lee Hyson for help with data analysis, and Eric Pearlman, Richard Ransohoff, and Richard Zigmond for helpful discussions. This work was supported by grants from The Research Institute of University Hospitals of Cleveland, Research to Prevent Blindness (Departmental Grant; Senior Scientific Investigator Award to J.D.P.), the Knight Templar Eye Research Foundation (S.K.), the Muscular Dystrophy Association USA (J.D.P.), and NIH Grants R01 EY09834 (J.D.P.), R01 EY12779 (J.D.P.), and P30 EY11373. J.D.P. is also supported by funding from the Carl F. Asseff, M.D. Professorship in Ophthalmology.",

year = "2003",

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doi = "10.1016/s0960-8966(02)00242-0",

language = "English",

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T1 - Persistent over-expression of specific CC class chemokines correlates with macrophage and T-cell recruitment in mdx skeletal muscle

AU - Porter, John D.

AU - Guo, Wei

AU - Merriam, Anita P.

AU - Khanna, Sangeeta

AU - Cheng, Georgiana

AU - Zhou, Xiaohua

AU - Andrade, Francisco H.

AU - Richmonds, Chellah

AU - Kaminski, Henry J.

N1 - Funding Information: We thank Patrick Leahy, Marty Veigl, and the Ireland Cancer Center Gene Expression Array Core Facility for DNA microarray assistance, Denney Hatala for immunocytochemistry, Beth Ann Benetz for assistance with illustrations, Lee Hyson for help with data analysis, and Eric Pearlman, Richard Ransohoff, and Richard Zigmond for helpful discussions. This work was supported by grants from The Research Institute of University Hospitals of Cleveland, Research to Prevent Blindness (Departmental Grant; Senior Scientific Investigator Award to J.D.P.), the Knight Templar Eye Research Foundation (S.K.), the Muscular Dystrophy Association USA (J.D.P.), and NIH Grants R01 EY09834 (J.D.P.), R01 EY12779 (J.D.P.), and P30 EY11373. J.D.P. is also supported by funding from the Carl F. Asseff, M.D. Professorship in Ophthalmology.

PY - 2003/3

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N2 - 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-1γ. 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.

AB - 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-1γ. 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.

KW - Chemokine

KW - Chemotaxis

KW - Mdx

KW - Muscular dystrophy

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Persistent over-expression of specific CC class chemokines correlates with macrophage and T-cell recruitment in mdx skeletal muscle

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

Access to Document

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