title: Interleukin (IL)11 mediates protein secretion and modification in human extravillous trophoblasts.
abstract: BACKGROUND
  Human trophoblast invasion and differentiation are essential for a successful pregnancy outcome. Dysregulation of these processes can lead to placental pathologies such as pre-eclampsia. The molecular mechanisms; however, are poorly understood. Interleukin (IL)11--a cytokine that regulates endometrial epithelial cell adhesion, trophoblast motility and invasion during implantation--may be involved in some of these processes.
  
  
  RESULTS
  The effect of IL11 on protein expression was investigated in trophoblastic HTR8/SVneo cells and primary extravillous trophoblasts (EVTs) purified from first- trimester placentas. Two-dimension (2D)-differential in-gel electrophoresis analyses revealed that 731 spots were significantly differentially regulated by IL11 in HTR8/SVneo cells: seven spots were analyzed by liquid chromatography-tandem mass spectrometry and 14 unique proteins identified. Protein disulfide isomerase family A, member 3 (PDIA3; endoplasmic reticulum p57) and glucose-regulated protein 78 (GRP78) were further validated to be regulated by IL11 in HTR8/SVneo and primary EVT. One dimension western blot analysis confirmed that PDIA3 was down-regulated in EVT. 2D western blot analysis revealed that GRP78 was post-translationally modified following IL11 treatment. Moreover, IL11 stimulated the secretion of GRP78 in EVT.
  
  
  CONCLUSIONS
  Data suggest that IL11, possibly via signal transducers and activators of transcription 3 signaling pathway, regulates PDIA3 protein expression and modification/secretion of GRP78. This is the first study to identify PDIA3 and GRP78 as IL11 targets in invasive trophoblasts and identifies a possible mechanism by which IL11 regulates trophoblast function.
authors.affiliation: Prince Henry's Institute of Medical Research, PO Box 5152, Clayton, Victoria 3168, Australia. stefan.sonderegger@princehenrys.org
authors.forename: Stefan
authors.initials: S
authors.lastname: Sonderegger
authors.forename: Joanne
authors.initials: J
authors.lastname: Yap
authors.forename: Ellen
authors.initials: E
authors.lastname: Menkhorst
authors.forename: Gareth
authors.initials: G
authors.lastname: Weston
authors.forename: Peter G
authors.initials: PG
authors.lastname: Stanton
authors.forename: Evdokia
authors.initials: E
authors.lastname: Dimitriadis
mesh_terms: D018929:Cell Culture Techniques; D002853:Chromatography, Liquid / Q000379:methods; D015180:Electrophoresis, Gel, Two-Dimensional / Q000379:methods; D000091342:Endoplasmic Reticulum Chaperone BiP; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D006360:Heat-Shock Proteins / Q000096:biosynthesis; D006801:Humans; D017370:Interleukin-11 / Q000378:metabolism / Q000502:physiology*; D013058:Mass Spectrometry / Q000379:methods; D008954:Models, Biological; D010920:Placenta / Q000378:metabolism; D011247:Pregnancy; D011261:Pregnancy Trimester, First; D019704:Protein Disulfide-Isomerases / Q000096:biosynthesis*; D011499:Protein Processing, Post-Translational; D014327:Trophoblasts / Q000166:cytology* / Q000378:metabolism
chemical_list: D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; D006360:Heat-Shock Proteins; D017370:Interleukin-11; D019704:Protein Disulfide-Isomerases; C085868:PDIA3 protein, human