title: Activin A is stimulated by tumor necrosis factor-alpha and modulates collagen gene expression in human amniotic cells.
abstract: BACKGROUND
  Accumulating evidence supports the idea of activin A as a modulator of inflammation. In human pregnancy, elevated activin A concentrations in amniotic fluid are reported in women with intra-amniotic infection and inflammation- induced pre-term birth.
  
  
  OBJECTIVE
  To test the hypothesis that activin A was involved in the pathophysiology of amnionitis, we evaluated the effects of tumor necrosis factor-α and lipopolysaccharide on activin A production in human amniotic epithelial cells, and the effects of activin A on the expression of collagen mRNA in amniotic mesenchymal cells.
  
  
  METHODS
  Amniotic membranes were obtained from patients without systemic disease, signs of premature delivery or fetal complications, during elective cesarean sections at term. Amniotic epithelial cells and mesenchymal cells were separately obtained by enzymatic digestion and cultured. Activin A was measured by enzyme-linked immunosorbent assay and collagen mRNA levels were assessed by quantitative PCR.
  
  
  RESULTS
  Amniotic epithelial cells produced activin A in a cell density- and time-dependent manner. Tumor necrosis factor- α enhanced activin A production in a time-dependent (48-120 h) and dose-dependent (10-300 ng/ml) manner in amniotic epithelial cells. Lipopolysaccharide also stimulated activin A production, but the effect was less prominent. In amniotic mesenchymal cells, the effect of activin A on the expression of type I and type III collagen mRNA was suppressive.
  
  
  CONCLUSIONS
  Tumor necrosis factor-α and lipopolysaccharide stimulated activin A production in amniotic epithelial cells, and activin A modulated expression of collagen mRNA in amniotic mesenchymal cells. These results support the idea that activin A is involved in the pathophysiology of amnionitis.
authors: Department of Laboratory Sciences, Graduate School of Health Sciences, Gunma University, 3-39-22 Showa, Maebashi, Gunma 371-8514, Japan. abe@gunma-u.ac.jp
authors: Y
authors: Y
authors: Abe
authors: M
authors: M
authors: Komatsubara
authors: M
authors: M
authors: Saito
authors: M
authors: M
authors: Toda
authors: H
authors: H
authors: Shinozaki
authors: T
authors: T
authors: Tamura
authors: Y
authors: Y
authors: Kasahara
authors: H
authors: H
authors: Sedakata
authors: T
authors: T
authors: Minegishi
mesh_terms: D028341:Activins / Q000096:biosynthesis / Q000378:metabolism*; D000650:Amnion / Q000166:cytology / Q000378:metabolism*; D002478:Cells, Cultured; D002821:Chorioamnionitis / Q000503:physiopathology; D024042:Collagen Type I / Q000096:biosynthesis*; D024061:Collagen Type III / Q000096:biosynthesis*; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D006801:Humans; D008648:Mesoderm / Q000378:metabolism; D011247:Pregnancy; D012333:RNA, Messenger / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology / Q000502:physiology*
chemical_list: D024042:Collagen Type I; D024061:Collagen Type III; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; C422405:activin A; D028341:Activins
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