Increased expression of epidermal IL-8 receptor in psoriasis. Down-regulation by FK-506 in vitro.

Abstract

IL-8 is a chemotactic cytokine with proinflammatory and growth-promoting activities. Recently it has been shown to influence several functions of keratinocytes, including HLA-DR expression, chemotaxis, and proliferation by binding to a specific receptor. Because psoriasis vulgaris is characterized by epidermal hyperproliferation and infiltration of inflammatory cells, we investigated the expression of IL-8 and its receptor in normal and psoriatic epidermis using semiquantitative reverse-transcriptase-polymerase chain reaction. In addition the mRNA levels of the proto-oncogenes c-ras, c-raf, c-myc, and HER-2 were also investigated 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 psoriatic epidermis. There was no significant difference in the protooncogene mRNA levels. In order to test the relevance of the massively increased IL-8R levels in psoriatic epidermis, we investigated the effect of the antipsoriatic drug FK-506 on specific IL-8 and IL-8R mRNA expression. FK-506 dose dependently inhibited IL-8R expression and function. Our data suggest that in psoriatic skin, elevated IL-8 levels and markedly increased IL-8R expression may act in concert to induce the cardinal signs of psoriasis--epidermal hyperproliferation and leukocyte infiltration. IL-8R may prove a molecular target for antipsoriatic drugs such as FK-506.

Interleukins 20 and 8 – less widely known cytokines in psoriasis

“…[ 134 ], who reported the downregulation of IL-8 mRNA in psoriasis lesions in patients on oral tacrolimus treatment after effective therapy. However, no reduction of IL-8R was observed in the same post-treatment biopsies, which is in contrast to an in vitro study in which tacrolimus was found to inhibit expression of the IL-8 receptor in human keratinocytes as compared with untreated cells [ 116 ]. A similar reduction in IL-8 mRNA expression was induced by ustekinumab, infliximab and etanercept in the responder tissue of lesional psoriatic skin compared with baseline [ 73 , 74 , 81 , 119 , 135 ].…”

“…IL-8 mRNA was found to be elevated in skin biopsies taken from psoriasis plaques compared with samples from healthy volunteers [ 91 , 114 – 118 ]. Similarly, lesional tissue from psoriatic patients was found to demonstrate increased IL-8 mRNA expression compared with uninvolved biopsy specimens [ 73 , 74 , 116 , 118 – 121 ]. Various other studies have noted upregulation of IL-8 in psoriatic tissue [ 122 , 123 ].…”

“…A marked increase in the epidermal expression of IL-8R has been noted in lesions in psoriasis compared to both normal and/or uninvolved skin [ 116 , 126 ]. Beljaards et al .…”