title: Interleukin-1 alpha, epidermal growth factor, and transforming growth factor-beta exhibit differential kinetics on endothelin-1 synthesis in amnion cells.
abstract: OBJECTIVE
  To investigate the effects of three cytokines, interleukin-1 alpha (IL-1 alpha), epidermal growth factor (EGF), and transforming growth factor-beta (TGF-beta), on the regulation of endothelin-1 (ET-1) mRNA and protein production in human amnion cells.
  
  
  METHODS
  Human amnion cells were harvested from uncomplicated pregnancies undergoing elective cesarean delivery at term and grown in primary monolayer culture. Cells were treated with IL-1 alpha, EGF, and TGF-beta for dose-response and time course experiments. Northern analysis was used to determine ET-1 mRNA expression, and enzyme-linked immunosorbent assay was used for ET-1 peptide determination.
  
  
  RESULTS
  Interleukin-1 alpha, EGF, and TGF-beta induced the expression of ET-1 mRNA and protein in a dose- and time-dependent fashion. The kinetics of ET-1 mRNA production did not differ markedly with respect to the inducing cytokine, but the kinetics of ET-1 protein production was quite different. Interleukin-1 alpha and EGF stimulated a rapid increase in ET-1 that peaked by 24 hours, and the levels declined to just above the detection limit by 72 hours. In contrast, TGF-beta-stimulated cells showed modest ET-1 production at early times (4-24 hours) and then gradually increased and peaked at 72 hours.
  
  
  CONCLUSIONS
  Cytokines modulate the expression of ET-1 mRNA and its cognate protein in human amnion cells. The differential kinetics of ET-1 peptide expression in amnion cells suggests that ET metabolism as well as synthesis contribute to the net expression of endothelin in amnion.
authors.affiliation: Department of Obstetrics and Gynecology, Ohio State University, College of Medicine, Columbus 43210, USA.
authors.forename: D S
authors.initials: DS
authors.lastname: McKenna
authors.forename: P
authors.initials: P
authors.lastname: Samuels
authors.forename: P D
authors.initials: PD
authors.lastname: Zimmerman
authors.forename: D A
authors.initials: DA
authors.lastname: Kniss
mesh_terms: D000650:Amnion / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D019332:Endothelin-1 / Q000096:biosynthesis* / Q000187:drug effects / Q000235:genetics; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D018507:Gene Expression Regulation, Developmental / Q000235:genetics*; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D007700:Kinetics; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
chemical_list: D019332:Endothelin-1; D007375:Interleukin-1; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D004815:Epidermal Growth Factor