title: Interleukin-1 and tumor necrosis factor stimulate arachidonic acid release and phospholipid metabolism in human myometrial cells.
abstract: OBJECTIVE
  Our aim was to evaluate the effects of the cytokines interleukin-1 and tumor necrosis factor on arachidonic acid release in human myometrial cells.
  
  
  METHODS
  Primary monolayer cultures of human myometrial cells prelabeled with tritiated arachidonic acid were exposed to interleukin-1 or tumor necrosis factor for varying periods and the release of tritiated arachidonic acid and its loss from phospholipids were measured by radiochromatography. To gain some information on the biologic action of interleukin-1 the contractile response to oxytocin was measured in myometrial strips preincubated with this cytokine. Data were statistically evaluated with analysis of variance or Student's test.
  
  
  RESULTS
  Both cytokines caused a dose-dependent increase in tritiated arachidonate release that was suppressed by the protein synthesis inhibitor cycloheximide. Tritiated arachidonic acid release was maximal after 24 hours of stimulation with interleukin-1. Both interleukin-1 and tumor necrosis factor stimulated the release of the isotopically labeled fatty acid from phosphatidylcholine. In addition, interleukin-1 also increased the loss of arachidonic acid from phosphatidic acid and significantly potentiated the oxytocin-evoked myometrial contractility.
  
  
  CONCLUSIONS
  Both interleukin-1 and tumor necrosis factor enhance arachidonic acid release, probably by inducing the synthesis of phospholipase A2 and possibly other enzymes involved in the metabolism of phospholipids. In turn, arachidonic acid itself may act as a second messenger, synergizing with other uterotonic agents, as well as serving as the precursor for prostaglandins and various other bioactive eicosanoids.
authors.affiliation: Department of Obstetrics and Gynecology, St. Louis, University School of Medicine, St. Mary's Health Center, MO.
authors.forename: M
authors.initials: M
authors.lastname: Molnár
authors.forename: R
authors.initials: R
authors.lastname: Romero
authors.forename: F
authors.initials: F
authors.lastname: Hertelendy
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D016718:Arachidonic Acid / Q000096:biosynthesis*; D002478:Cells, Cultured; D003513:Cycloheximide / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007375:Interleukin-1 / Q000502:physiology*; D009215:Myometrium / Q000166:cytology / Q000378:metabolism*; D010121:Oxytocin / Q000494:pharmacology; D010743:Phospholipids / Q000378:metabolism*; D011247:Pregnancy; D017697:Premenopause; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*; D014590:Uterine Contraction / Q000187:drug effects
chemical_list: D007375:Interleukin-1; D010743:Phospholipids; D014409:Tumor Necrosis Factor-alpha; D016718:Arachidonic Acid; D010121:Oxytocin; D003513:Cycloheximide