INCREASED EXPRESSION OF EPIDERMAL IL-8 RECEPTOR IN PSORIASIS - DOWN-REGULATION BY FK-506 IN-VITRO

IL-8 is a chemotactic cytokine with proinflammatory and growth-promoti ng activities. Recently it has been shown to influence several functio ns of keratinocytes, including HLA-DR expression, chemotaxis, and prol iferation by binding to a specific receptor. Because psoriasis vulgari s is characterized by epidermal hyperproliferation and infiltration of inflammatory cells, we investigated the expression of IL-8 and its re ceptor in normal and psoriatic epidermis using semiquantitative revers e-transcriptase-polymerase chain reaction. In addition the mRNA levels of the proto-oncogenes c-ras, c-raf, c-myc, and HER-2 were also inves tigated as potential growth-promoting stimuli in psoriatic epidermis. IL-8 mRNA was only detected in lesional psoriatic epidermis, and IL-8R -specific mRNA was found to be 10 times increased in lesional psoriati c epidermis. There was no significant difference in the proto-oncogene mRNA levels. In order to test the relevance of the massively increase d IL-8R levels in psoriatic epidermis, we investigated the effect of t he antipsoriatic drug FK-506 on specific IL-8 and IL-8R mRNA expressio n. FK-506 dose dependently inhibited IL-8R expression and function. Ou r data suggest that in psoriatic skin, elevated IL-8 levels and marked ly increased IL-8R expression may act in concert to induce the cardina l signs of psoriasis-epidermal hyperproliferation and leukocyte infilt ration. IL-8R may prove a molecular target for antipsoriatic drugs suc h as FK-506.