Wj. Lukiw et al., The interleukin-1 type 2 receptor gene displays immediate early gene responsiveness in glucocorticoid-stimulated human epidermal keratinocytes, J BIOL CHEM, 274(13), 1999, pp. 8630-8638
Human epidermal keratinocytes (HEKs) in primary culture (P2-P4) were used t
o study glucocorticoid (GC)mediated transcription of the genes encoding the
constitutively expressed interleukin-1 type 1 receptor (IL-1R1) and the in
ducible interleukin-1 type 2 receptor (IL-1R2). Utilizing Northern dot blot
analysis and a quantitative reverse transcription-polymerase chain reactio
n protocol for IL-1R1 and IL-1R2, dexamethasone and, in particular, the bud
esonide epimer R were shown to effectively and rapidly induce transcription
from the IL-IR2 gene when compared with IL-1R1 or beta-actin RNA message l
evels in the same sample. Southern blot analysis of newly generated IL-1R2
reverse transcription-polymerase chain reaction products using end-labeled
IL-1R2 intron probes suggested that GC enhancement of IL-1R2 expression was
regulated primarily at the level of de novo transcription. GC-induced IL-1
R2 gene transcription displayed features characteristic of a classical imme
diate early gene response, including a signal transduction function, a rela
tively low basal abundance, a rapid, transient induction, cycloheximide sup
erinduction, actinomycin D suppression, and a rapid decay of IL-1R2 RNA mes
sage. Parallel time course kinetic analysis of IL-1R2 RNA message levels wi
th Western immunoblotting revealed tight coupling of de novo IL-IR2 gene tr
anscription with translation of the IL-1R2 RNA message; a newly synthesized
(similar to 46-kDa) IL-1RS protein was detected in the HEK growth medium a
s early as 1 h after budesonide epimer R treatment. These data indicate tha
t different GC compounds can variably up-regulate the IL-1R2 response in HE
Ks through transcription-mediated mechanisms and, for the first time, sugge
st that a gene encoding a soluble cytokine receptor can respond like an imm
ediate early gene.