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American Journal of Pathology, Vol 145, 1048-1056, Copyright © 1994 by American Society for Investigative Pathology
REGULAR ARTICLES |
RW Groves, L Sherman, H Mizutani, SK Dower and TS Kupper
Harvard Skin Disease Research Center, Harvard Medical School, Brigham and Women's Hospital, Boston, Massachusetts.
Normal human epidermis is a rich source of biologically active interleukin-1 alpha (IL-1 alpha). Keratinocytes both synthesize this cytokine and respond to it via cell surface receptors (IL-1R), suggesting that the IL-1 system may play an important role in normal epidermal physiology and inflammation. In this study, we have examined the expression of IL-1R in normal and psoriatic epidermis, as judged at a functional level by the capacity to bind 125I-labeled IL-1 alpha (the principal IL-1 species present in epidermis) and by immunostaining with antibodies specific for each species of IL-1R. IL-1R was not readily detectable by either technique in normal, freshly isolated human epidermis. However, in lesional psoriasis or normal epidermis after 24 hours of organ culture, expression of IL-1R was dramatically induced, especially in basal keratinocytes. Immunostaining and antibody blocking studies demonstrated the induced IL-1R to be the type II species, a nonsignal transducing molecule previously demonstrated only on leukocytes. The Ka of this receptor was comparable to that previously demonstrated in vitro. mRNA for both species of IL-1R could be demonstrated by reverse transcriptase-polymerase chain reaction in fresh and cultured epidermis. These in vivo findings were confirmed in culture, where normal human keratinocytes expressed few IL-1R at rest but large numbers of type II IL-1R after activation by phorbol ester or interferon-gamma. We conclude that under resting conditions, epidermal expression of IL-1R is low. However, the potential for keratinocytes in vivo to express large numbers of the nonsignal transducing type II IL- 1R is evident from both organ cultured and psoriatic epidermis. The in vitro induction of keratinocyte IL-1R by interferon-gamma suggests that this cytokine may be involved in the induction of type II IL-1R in inflammatory skin disease. The presence of bioactive IL-1 in epidermis, coupled with the inducible expression of the decoy type II IL-1R, indicates the existence of a highly regulated system of autocrine stimulation of keratinocytes by IL-1.
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