Regulation of class I MHC expression in skeletal muscle: deleterious effect of aberrant expression on myogenesis.
Aberrant expression of class I major histocompatibility complex (MHC) occurs on myofibers in inflammatory myopathies. The mechanisms responsible for such expression are unknown. Here we show that class I MHC expression is developmentally regulated during muscle regeneration with significant levels only in myoblasts. Injection of gamma-IFN plasmid leads to muscle inflammation, induction of class I MHC in regenerating, but not mature myofibers, and attenuation of regeneration. Gene transfer of class I MHC in vivo and in vitro also attenuates muscle differentiation. Thus, cytokines may contribute to the pathogenesis of inflammatory myopathies by upregulating class I MHC and leading to deleterious effects on muscle repair.
Pavlath
Grace K
GK
Department of Pharmacology, Emory University School of Medicine, Room 5027, O.W. Rollins Research Bldg., Atlanta, GA 30322, USA. gpavlat@emory.edu
D000818:Animals; D002454:Cell Differentiation / Q000276:immunology; D015870:Gene Expression / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018485:Muscle Fibers, Skeletal / Q000276:immunology* / Q000473:pathology; D018482:Muscle, Skeletal / Q000473:pathology / Q000502:physiology*; D009220:Myositis / Q000276:immunology* / Q000473:pathology; D012038:Regeneration / Q000276:immunology*; D013047:Specific Pathogen-Free Organisms
D015395:Histocompatibility Antigens Class I; D007371:Interferon-gamma