Interleukin-6 up-regulates the oxytocin receptor in cultured uterine smooth muscle cells

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.