Interleukin-1 receptors type I and type II are differentially regulated in human keratinocytes by ultraviolet B radiation.
Since regulation of keratinocyte IL-1 receptor expression is likely to have a major impact on the biologic effects of IL-1 on epidermal cells, we examined expression, regulation, and function of IL-1R in cultured human keratinocytes. By reverse transcriptase polymerase chain reaction, human keratinocytes were shown to express IL-1 receptor type I (IL-1RI) and IL-1 receptor type II (IL-1RII). Human keratinocyte IL-1RI mRNA expression was dependent on the differentiation state of the cell and was regulated by ultraviolet B (UVB) radiation, which initially decreased but later increased IL-1RI expression. This UVB-induced biphasic modulation of IL-1RI expression was mediated by an autocrine mechanism involving endogenously produced IL-1alpha and IL-1RI. Increased expression of IL-1RI in UVB-irradiated or IL-1alpha-stimulated keratinocytes was functionally important, because it endowed these cells with the capacity to upregulate expression of the intercellular adhesion molecule (ICAM)-1 upon IL-1alpha stimulation. Keratinocyte IL-1RII expression was regulated by UVB irradiation in an inverse manner. Significant and rapid upregulation of IL-1RII was observed within 1 h after UVB irradiation and gradually decreased to background levels within 24 h. Inverse regulation of IL-1RII versus IL-1RI was associated with opposite functions, because blocking of IL-1RII enhanced IL-1alpha effects on induction of ICAM-1 expression. These studies demonstrate that IL-1 responsiveness of UVB-irradiated keratinocytes critically depends on regulation of IL-1RI expression and that IL-1RII serves as a "decoy" receptor for IL-1, limiting rather than promoting IL-1-mediated effects.
Grewe
M
M
Clinical and Experimental Photodermatology, Department of Dermatology, Heinrich-Heine-University, Düsseldorf, Germany.
Gyufko
K
K
Budnik
A
A
Ruzicka
T
T
Olaizola-Horn
S
S
Berneburg
M
M
Krutmann
J
J
D002478:Cells, Cultured; D006801:Humans; D007231:Infant, Newborn; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D007375:Interleukin-1 / Q000494:pharmacology; D015603:Keratinocytes / Q000187:drug effects* / Q000378:metabolism; D016133:Polymerase Chain Reaction / Q000379:methods; D012333:RNA, Messenger / Q000378:metabolism; D012194:RNA-Directed DNA Polymerase; D017472:Receptors, Interleukin-1 / Q000378:metabolism / Q000528:radiation effects*; D014407:Tumor Cells, Cultured; D014466:Ultraviolet Rays
D007375:Interleukin-1; D012333:RNA, Messenger; D017472:Receptors, Interleukin-1; D018799:Intercellular Adhesion Molecule-1; D012194:RNA-Directed DNA Polymerase