title: Production of oxytocin receptor and cytokines in primary uterine smooth muscle cells cultivated under inflammatory conditions.
abstract: OBJECTIVE
  We studied the production of the oxytocin receptor and interleukins in human uterine smooth muscle cells cultured in vitro in the presence of cytokines that were shown to be elevated in gestational diseases such as intrauterine infections and chorioamnionitis.
  
  
  METHODS
  Human uterine smooth muscle cells were cultured in the absence or presence of interleukin-1beta (IL-1beta), interleukin-6 (IL-6), tumor necrosis factor alpha (TNFalpha), or lipopolysaccharide (LPS). Additionally, cells were cultivated under hypoxic conditions (3.5% oxygen). After 6, 12, 24, and 48 hours of incubation, oxytocin receptor mRNA was measured from total RNA using quantitative, competitive reverse transcriptase-polymerase chain reaction. Secreted cytokines (IL-1beta, IL-6, or IL-8) were quantitated from supernatants after 6, 12, 24, and 48 hours of stimulation by commercially available enzyme-linked immunosorbent assay.
  
  
  RESULTS
  In nonstimulated cultures basal secretion of IL-1beta, IL-6, and IL-8 was detectable. Supplementation of IL-1beta induced a statistically significant decrease in oxytocin receptor mRNA abundance, whereas IL-6, TNFalpha, LPS, or hypoxia did not significantly affect oxytocin receptor gene expression. The cytokines IL-1 and TNFalpha induced IL-6 and IL-8 release, whereas secretion of the two interleukins was not altered in the presence of LPS or hypoxia. Expression of IL-1beta was not significantly induced under inflammatory or hypoxic culture conditions.
  
  
  CONCLUSIONS
  The constitutive and cytokine-inducible expression of interleukins from uterine smooth muscle cells suggests that the myometrium may contribute to the overall production of inflammatory mediators in the uterus that are thought to govern term- or infection-induced preterm labor. Down-regulation of the oxytocin receptor under IL-1beta in myometrial cells may indicate that initiation and maintenance of labor could be partially limited under severe inflammatory conditions such as chorioamnionitis.
authors.affiliation: Department of Obstetrics and Gynecology, General Hospital, University of Vienna, Vienna, Austria.
authors.forename: Hanns
authors.initials: H
authors.lastname: Helmer
authors.forename: Ulrike
authors.initials: U
authors.lastname: Tretzmüller
authors.forename: Mathias
authors.initials: M
authors.lastname: Brunbauer
authors.forename: Andrea
authors.initials: A
authors.lastname: Kaider
authors.forename: Peter
authors.initials: P
authors.lastname: Husslein
authors.forename: Martin
authors.initials: M
authors.lastname: Knöfler
mesh_terms: D002478:Cells, Cultured; D002821:Chorioamnionitis / Q000276:immunology; D005260:Female; D006801:Humans; D000860:Hypoxia; D007378:Interleukins / Q000096:biosynthesis* / Q000378:metabolism; D009215:Myometrium / Q000276:immunology / Q000378:metabolism*; D011247:Pregnancy; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D018045:Receptors, Oxytocin / Q000096:biosynthesis* / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D007378:Interleukins; D012333:RNA, Messenger; D018045:Receptors, Oxytocin