In vivo expression of cytokine receptor mRNA in atopic dermatitis.
BACKGROUND
Atopic dermatitis (AD) is a chronic inflammatory skin disease with immunopathologic features that vary depending on the duration of the lesion. Acute lesions are associated with a T-cell infiltrate and a high expression of IL-4 mRNA compared with chronic lesions, uninvolved AD skin, or skin from normal control subjects. Chronic lesions are rich in eosinophils and monocyte/macrophages and contain a greater number of IL-5, granulocyte-macrophage colony-stimulating factor (GM-CSF), and IL-12 (p40) mRNA-positive cells.


OBJECTIVE
In this study, we investigated the mRNA expression of the IL-4 receptor (IL-4Ralpha), IL-5Ralpha, GM-CSFRalpha, and IL-12Rbeta2 in biopsy specimens from acute and chronic AD lesions, uninvolved AD skin, normal skin, and psoriatic skin lesions.


METHODS
Cytokine receptor mRNA was examined in paraformaldehyde-fixed biopsy specimens with in situ hybridization with specific antisense riboprobes.


RESULTS
Acute and chronic skin lesions exhibited a significant increase in numbers of IL-5Rbeta and GM-CSFRalpha mRNA-positive cells compared with uninvolved AD skin and normal skin (P < .001). Chronic skin lesions had a significantly greater number of IL-5Ralpha and GM-CSFRalpha mRNA-positive cells when compared with acute AD skin (P < .001). In contrast, IL-4Ralpha mRNA expression was increased in acute but not chronic AD lesions compared with uninvolved and normal skin (P < .001). No significant differences were observed in numbers of IL-12Rbeta2 mRNA-positive cells when comparing acute AD, chronic AD, uninvolved AD, and normal skin. In psoriatic skin, the numbers of GM-CSFRalpha and IL-12Rbeta2 mRNA-positive cells were significantly increased compared with acute AD lesions, uninvolved skin, and normal control skin (P < .01).


CONCLUSIONS
These results demonstrate that acute AD is associated with a high expression of IL-4Ralpha, whereas IL-5Ralpha and GM-CSFRalpha mRNA are predominantly increased in chronic AD and to lesser extent in acute lesions. These findings support the biphasic role of IL-4, IL-5, and GM-CSF in the pathophysiology of AD.
Taha
R A
RA
Meakins-Christie Laboratories, McGill University, Montreal, Quebec, Canada.
Leung
D Y
DY
Ghaffar
O
O
Boguniewicz
M
M
Hamid
Q
Q
D000328:Adult; D003876:Dermatitis, Atopic / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D015870:Gene Expression; D006801:Humans; D008875:Middle Aged; D012333:RNA, Messenger; D018121:Receptors, Cytokine / Q000096:biosynthesis / Q000235:genetics*; D016187:Receptors, Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics; D018123:Receptors, Interleukin / Q000235:genetics; D053707:Receptors, Interleukin-12; D019948:Receptors, Interleukin-4 / Q000235:genetics; D053649:Receptors, Interleukin-5
D012333:RNA, Messenger; D018121:Receptors, Cytokine; D016187:Receptors, Granulocyte-Macrophage Colony-Stimulating Factor; D018123:Receptors, Interleukin; D053707:Receptors, Interleukin-12; D019948:Receptors, Interleukin-4; D053649:Receptors, Interleukin-5