Cyclosporin inhibits intercellular adhesion molecule-1 expression and reduces mast cell numbers in the asebia mouse model of chronic skin inflammation.
The asebia mouse represents a spontaneous mutation in BALB/c mice leading to hyperplasia of the epidermis and chronic inflammatory dermal changes including enhanced cellularity, oedema and elevated mast cell numbers. We demonstrated that asebia mice have constitutively elevated intercellular adhesion molecule-1 (ICAM-1) mRNA expression, which is not detectable in the wild type, and that dermal mast cell numbers were 3.1-fold higher than the wild type (P < 0.001). We utilized this model to explore the anti-inflammatory effects of cyclosporin A (CsA). After 3 weeks subcutaneous injection with 5 or 10 mg/kg CsA the expression of ICAM-1 mRNA was determined by semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) and was found to be decreased 2.7-fold (P < 0.001) and three-fold (P < 0.001) relative to controls for 5 and 10 mg/kg treatments, respectively. Dermal mast cell counts were dose-dependently decreased by CsA. Mast cells, visualized by toluidine blue staining, decreased 4.5-fold with 10 mg/kg CsA (P < 0.001) bringing them down to numbers typical of the wild type. CsA also appeared to stabilize mast cell histamine content. Histological examination of haematoxylin-eosin-stained sections revealed that CsA treatment restored the wild-type skin phenotype decreasing epidermal hyperplasia, dermal cellularity and oedema. Thus, CsA exhibits a wide range of anti-inflammatory effects including reduction of ICAM-1 expression and mast cell numbers, and may be useful in the treatment of mast cell-mediated dermatoses.
Oran
A
A
Division of Dermatology, University of Toronto, Sunnybrook Health Sciences Centre, Ontario, Canada.
Marshall
J S
JS
Kondo
S
S
Paglia
D
D
McKenzie
R C
RC
D000818:Animals; D002452:Cell Count / Q000187:drug effects; D016572:Cyclosporine / Q000494:pharmacology* / Q000627:therapeutic use; D003872:Dermatitis / Q000188:drug therapy* / Q000276:immunology; D004195:Disease Models, Animal; D015870:Gene Expression / Q000187:drug effects; D006632:Histamine / Q000378:metabolism; D007166:Immunosuppressive Agents / Q000494:pharmacology* / Q000627:therapeutic use; D018799:Intercellular Adhesion Molecule-1 / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D008297:Male; D008407:Mast Cells / Q000187:drug effects*; D051379:Mice; D008807:Mice, Inbred BALB C; D010641:Phenotype; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics
D007166:Immunosuppressive Agents; D012333:RNA, Messenger; D018799:Intercellular Adhesion Molecule-1; D006632:Histamine; D016572:Cyclosporine