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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 hypothesize that infection up‐regulates OTR expression through IL‐6‐induced transcription factors.  METHOD OF STUDY: 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 I‐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.