Immunopathogenic pathways in canine inflammatory myopathies resemble human myositis.
Progress in the treatment of inflammatory myopathies is impeded by the lack of suitable animal models. Inflammatory myopathies occur spontaneously in the dog, are a heterogeneous group of disorders, and are more common than in humans. Clinical signs of weakness and muscle atrophy are reliably present, and there are histological and immunohistological similarities to forms of human myositis. In this study, microarray technology followed by quantitative real-time PCR and immunohistochemistry on muscle biopsy sections was used to investigate gene expression in cases of canine inflammatory myopathies. Several genes involved with innate and adaptive immunity were highly upregulated including those that participate in macrophage and dendritic cell activation and migration, and antigen processing and presentation. Other genes including those that participate in B cell growth, development, migration and activation, immunoglobulin genes, genes in pro-inflammatory and anti-inflammatory pathways, and genes involved with tissue remodeling were upregulated. In previous reports utilizing microarray technology in human myositis, there was activation of similar pathways involved in the immune response. This study strengthens the argument that forms of canine myositis may be important animal models of human myositis and suggests useful biomarkers for therapeutic response using the dog in pre-clinical trials.
Shelton
G Diane
GD
Department of Pathology, University of California, San Diego, La Jolla, CA 92093-0709, USA. gshelton@ucsd.edu
Hoffman
Eric P
EP
Ghimbovschi
Svetlana
S
Peters
Iain R
IR
Day
Michael J
MJ
Mullins
Marissa
M
Moore
Peter F
PF
Nagaraju
Kanneboyina
K
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D001706:Biopsy / Q000662:veterinary; D003171:Complement Pathway, Classical; D016207:Cytokines / Q000235:genetics / Q000276:immunology; D004195:Disease Models, Animal; D004283:Dog Diseases / Q000276:immunology* / Q000473:pathology; D004285:Dogs; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007136:Immunoglobulins / Q000276:immunology; D007150:Immunohistochemistry; D008297:Male; D018482:Muscle, Skeletal / Q000276:immunology* / Q000473:pathology; D009220:Myositis / Q000276:immunology / Q000473:pathology / Q000662:veterinary*; D020411:Oligonucleotide Array Sequence Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction
D016207:Cytokines; D007136:Immunoglobulins