title: Production of interleukin-1alpha by human endometrial stromal cells is triggered during menses and dysfunctional bleeding and is induced in culture by epithelial interleukin-1alpha released upon ovarian steroids withdrawal.
abstract: BACKGROUND
  Endometrial breakdown during menstruation and dysfunctional bleeding is triggered by the abrupt expression of matrix metalloproteinases (MMPs), including interstitial collagenase (MMP-1). The paracrine induction of MMP-1 in stromal cells via epithelium-derived IL-1alpha is repressed by ovarian steroids. However, the control by estradiol (E) and progesterone (P) of endometrial IL-1alpha expression and bioactivity remains unknown.
  
  
  OBJECTIVE
  Variations of endometrial IL-1alpha mRNA and protein along the menstrual cycle and during dysfunctional bleeding were determined using RT-PCR, in situ hybridization, and immunolabeling. The mechanism of EP control was analyzed using culture of explants, laser capture microdissection, and purified cells. Data were compared with expression changes of IL-1beta and IL-1 receptor antagonist.
  
  
  RESULTS
  IL-1alpha is synthesized by epithelial cells throughout the cycle but E and/or P prevents its release. In contrast, endometrial stromal cells produce IL-1alpha only at menses and during irregular bleeding in areas of tissue breakdown. Stromal expression of IL-1alpha, like that of MMP-1, is repressed by P (alone or with E) but triggered by epithelium-derived IL-1alpha released upon EP withdrawal.
  
  
  CONCLUSIONS
  Our experiments in cultured endometrium suggest that IL-1alpha released by epithelial cells triggers the production of IL-1alpha by stromal cells in a paracrine amplification loop to induce MMP-1 expression during menstruation and dysfunctional bleeding. All three steps of this amplification cascade are repressed by EP.
authors.affiliation: CELL Unit, de Duve Institute, UCL-75.41, B-1200 Bruxelles, Belgium.
authors.forename: Chrystel M
authors.initials: CM
authors.lastname: Pretto
authors.forename: Héloïse P
authors.initials: HP
authors.lastname: Gaide Chevronnay
authors.forename: Patricia B
authors.initials: PB
authors.lastname: Cornet
authors.forename: Christine
authors.initials: C
authors.lastname: Galant
authors.forename: Denis
authors.initials: D
authors.lastname: Delvaux
authors.forename: Pierre J
authors.initials: PJ
authors.lastname: Courtoy
authors.forename: Etienne
authors.initials: E
authors.lastname: Marbaix
authors.forename: Patrick
authors.initials: P
authors.lastname: Henriet
mesh_terms: D002478:Cells, Cultured; D004717:Endometrium / Q000187:drug effects / Q000378:metabolism*; D004848:Epithelium / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D012739:Gonadal Steroid Hormones / Q000494:pharmacology*; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D053582:Interleukin-1alpha / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D053583:Interleukin-1beta / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D008598:Menstruation / Q000235:genetics / Q000378:metabolism*; D008796:Metrorrhagia / Q000235:genetics / Q000378:metabolism*; D008954:Models, Biological; D009924:Organ Culture Techniques; D010053:Ovary / Q000378:metabolism; D019899:Paracrine Communication / Q000235:genetics / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism; D017154:Stromal Cells / Q000187:drug effects / Q000378:metabolism*
chemical_list: D012739:Gonadal Steroid Hormones; D053590:Interleukin 1 Receptor Antagonist Protein; D053582:Interleukin-1alpha; D053583:Interleukin-1beta; D012333:RNA, Messenger