PROBLEM: 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 hypothe
size that infection up-regulates OTR expression through IL-6-induced transc
ription factors.
METHOD OF STUDY: Primary cultures of human myometrium were treated for vari
ous time periods or with different concentrations of IL-6 and OTR mRNA as w
ell as OTR binding were measured by means of reverse transcription polymera
se chain reaction and I-125-ornithine-vasotocin-binding assay. To study und
erlying mechanisms of OTR changes with IL-6 treated, cells were also incuba
ted 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 b
inding 1.4-fold after 8 hr of cytokine stimulation. The IL-6-induced increa
se in binding was blocked by genistein and H7.
CONCLUSIONS: IL-6 up-regulates uterine OTR mRNA expression and binding capa
city in cultured human myocytes most likely through tyrosine and serine pho
sphorylation pathways involving the nuclear factor STAT-3.