Detection of interleukin-1 receptors in human epidermis. Induction of the type II receptor after organ culture and in psoriasis.
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.
Groves
R W
RW
Harvard Skin Disease Research Center, Harvard Medical School, Brigham and Women's Hospital, Boston, Massachusetts.
Sherman
L
L
Mizutani
H
H
Dower
S K
SK
Kupper
T S
TS
D001345:Autoradiography; D001483:Base Sequence; D017931:DNA Primers; D004817:Epidermis / Q000378:metabolism*; D006801:Humans; D007124:Immunoenzyme Techniques; D007375:Interleukin-1 / Q000378:metabolism; D015603:Keratinocytes / Q000378:metabolism; D008969:Molecular Sequence Data; D009924:Organ Culture Techniques; D016133:Polymerase Chain Reaction; D011565:Psoriasis / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D017472:Receptors, Interleukin-1 / Q000378:metabolism*
D017931:DNA Primers; D007375:Interleukin-1; D012333:RNA, Messenger; D017472:Receptors, Interleukin-1