Prednisolone decreases cellular adhesion molecules required for inflammatory cell infiltration in dystrophin-deficient skeletal muscle.
The mechanism of prednisolone's efficacy in the dystrophic pathology is unclear. Prednisolone's anti-inflammatory functions may be particularly important considering the significance of inflammatory cells in dystrophinopathy. In other pathologies, prednisolone's anti-inflammatory effects can be mediated by reducing cellular adhesion molecule (CAM) expression. The goal of this study was to examine the effects of prednisolone on inflammation and CAM expression in dystrophic muscle. Dystrophin-deficient, mdx mice were treated with 0.75 mg/kg prednisolone from 2 to 4 weeks of age. Prednisolone reduced macrophages (-59%, -57%), CD4(+) T-cells (-50%, -60%), CD8(+) T-cells (-58%, -48%), and eosinophils (-36%, -25%) in quadriceps and soleus muscles, respectively. Prednisolone-treated mice also exhibited decreased vascular P-selectin (-82%) and ICAM-1 (-52%) expression and fewer L-selectin (-79%) and ICAM-1 (-57%) expressing mononuclear cells in quadriceps. Prednisolone reduced sarcolemmal damage and degeneration as well. Our data show that prednisolone is an effective anti-inflammatory in dystrophic muscle and may function by modulating CAM expression.
Wehling-Henricks
Michelle
M
Department of Physiological Science, University of California, 5833 Life Science Building, Los Angeles, CA 90095-1527, USA.
Lee
James J
JJ
Tidball
James G
JG
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D000943:Antigens, Differentiation / Q000378:metabolism; D015704:CD4 Antigens / Q000378:metabolism; D016827:CD8 Antigens / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002452:Cell Count / Q000379:methods; D016189:Dystrophin / Q000172:deficiency*; D019040:E-Selectin / Q000378:metabolism; D004804:Eosinophils / Q000187:drug effects; D005260:Female; D007150:Immunohistochemistry / Q000379:methods; D007249:Inflammation / Q000188:drug therapy / Q000209:etiology; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects; D008297:Male; D051379:Mice; D018101:Mice, Inbred mdx; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism; D009135:Muscular Diseases / Q000188:drug therapy*; D019007:P-Selectin / Q000378:metabolism; D011239:Prednisolone / Q000627:therapeutic use*; D012038:Regeneration / Q000187:drug effects; D012508:Sarcolemma / Q000187:drug effects / Q000473:pathology; D014227:Triazines
D000893:Anti-Inflammatory Agents; D000943:Antigens, Differentiation; D015704:CD4 Antigens; D016827:CD8 Antigens; D015815:Cell Adhesion Molecules; D016189:Dystrophin; D019040:E-Selectin; D019007:P-Selectin; D014227:Triazines; C036763:monocyte-macrophage differentiation antigen; D018799:Intercellular Adhesion Molecule-1; C003213:Procion Brilliant Red M-2BS; D011239:Prednisolone