Interleukin-6 up-regulates the oxytocin receptor in cultured uterine smooth muscle cells.
OBJECTIVE
Intra-uterine infection results in the production of inflammatory cytokines, including interleukin-6 (IL-6). Increased oxytocin-receptor (OTR) concentrations are associated with the onset of preterm labor. We hypothesize that infection up-regulates OTR expression through IL-6-induced transcription factors.


METHODS
Primary cultures of human myometrium were treated for various time periods or with different concentrations of IL-6 and OTR mRNA as well as OTR binding were measured by means of reverse transcription polymerase chain reaction and 125I-ornithine-vasotocin-binding assay. To study underlying mechanisms of OTR changes with IL-6 treated, cells were also incubated with genistein or H7 (tyrosine and serine phosphorylation inhibitors), respectively.


RESULTS
OTR mRNA increased 2.5-fold after 4 hr of IL-6 treatment and OTR binding 1.4-fold after 8 hr of cytokine stimulation. The IL-6-induced increase in binding was blocked by genistein and H7.


CONCLUSIONS
IL-6 up-regulates uterine OTR mRNA expression and binding capacity in cultured human myocytes most likely through tyrosine and serine phosphorylation pathways involving the nuclear factor STAT-3.
Magee-Womens Research Institute, Pittsburgh, Pennsylvania 15213, USA.
P N
PN
Rauk
U
U
Friebe-Hoffmann
L D
LD
Winebrenner
J P
JP
Chiao
D005260:Female; D019833:Genistein / Q000494:pharmacology; D006801:Humans; D015850:Interleukin-6 / Q000494:pharmacology*; D009215:Myometrium / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D011247:Pregnancy; D011263:Pregnancy Trimester, Third; D018045:Receptors, Oxytocin / Q000096:biosynthesis*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation
D015850:Interleukin-6; D018045:Receptors, Oxytocin; D019833:Genistein