Ea. Kennard et al., INTERLEUKIN-1-BETA INDUCES CYCLOOXYGENASE-2 IN CULTURED HUMAN DECIDUAL CELLS, American journal of reproductive immunology [1989], 34(2), 1995, pp. 65-71
PROBLEM: The purpose of this study was to examine the hypothesis that
interleukin-1 beta (IL-1 beta)-elicited increases in decidual prostagl
andin E(2) and F-2 alpha (PGE(2) and PGF(2 alpha)) biosynthesis are du
e to the de novo expression of the inducible isoform of cyclooxygenase
(i.e., COX-2). METHOD: Primary human decidual cell cultures were esta
blished from term placentas delivered by cesarean section. After 8 day
s in vitro, when the cultures secreted immunoreactive prolactin, the c
ells were incubated for 24 h in serum-free medium, and then challenged
with IL-1 beta from 1 to 48 h. PGE(2) and PGF(2 alpha) content in the
media were measured by specific radioimmunoassays. RESULTS: IL-1 beta
stimulated a time-dependent enhancement in PGE(2) and PGF(2 alpha) pr
oduction, with PGF(2 alpha) synthesis predominating over PGE(2). IL-1
beta also induced a dose-dependent increase in the output of both arac
hidonic acid metabolites. When Northern blots of IL-1 beta-treated and
control cells were probed with cDNAs encoding either COX-1 or COX-2 i
soforms or an oligonucleotide probe encoding a portion of the human be
ta-actin, we detected a time-and dose-dependent increase in the steady
-state levels of COX-2, but not COX-1 or beta-actin mRNA transcripts.
Moreover, the expression of COX-2 mRNA in IL-1 beta-stimulated cells w
as superinduced by preincubation with cycloheximide, but completely ab
olished by actinomycin D. CONCLUSIONS: Taken together, the data sugges
t that COX-2 mRNA expression is largely responsible for the robust inc
rease in PG formation seen in IL-1 beta-treated decidual cells.