title: Progranulin shows cytoprotective effects on trophoblast cells in vitro but does not antagonize TNF-α-induced apoptosis.
abstract: OBJECTIVE
  The glycoprotein progranulin directly binds to TNF-receptors and thereby can antagonize the inflammatory effects of TNF-α. Here we analyzed the impact of both cytokines on cytotoxicity and viability of trophoblast cells.
  
  
  METHODS
  Isolated villous first trimester human trophoblast cells and the human choriocarcinoma cell line BeWo were treated with recombinant human progranulin and TNF-α. Analyses were performed by LDH- and MTT-assay and measurement of caspase-8-activity.
  
  
  RESULTS
  Progranulin treatment showed some cytoprotective effects on isolated trophoblast cells. However, TNF-α-induced apoptosis was not antagonized by addition of progranulin. Effects were similar, but more pronounced in BeWo cells.
  
  
  CONCLUSIONS
  The cytoprotective activity of progranulin on trophoblast cells in vitro was only weak and of doubtful biologic relevance. It was not able to antagonize TNF-α. Future studies should focus on possible paracrine activities of progranulin.
authors.affiliation: Department of Obstetrics and Gynecology, University of Rostock, Suedring 81, 18059, Rostock, Germany, johannes.stubert@uni-rostock.de.
authors.forename: Johannes
authors.initials: J
authors.lastname: Stubert
authors.forename: Kathrin
authors.initials: K
authors.lastname: Waldmann
authors.forename: Max
authors.initials: M
authors.lastname: Dieterich
authors.forename: Dagmar-Ulrike
authors.initials: DU
authors.lastname: Richter
authors.forename: Volker
authors.initials: V
authors.lastname: Briese
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D053181:Caspase 8 / Q000378:metabolism*; D002460:Cell Line / Q000187:drug effects*; D002822:Choriocarcinoma / Q000378:metabolism; D003601:Cytotoxicity Tests, Immunologic; D003602:Cytotoxicity, Immunologic; D005260:Female; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D011247:Pregnancy; D011261:Pregnancy Trimester, First; D000077153:Progranulins; D018124:Receptors, Tumor Necrosis Factor; D014327:Trophoblasts / Q000187:drug effects* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000009:adverse effects* / Q000378:metabolism; D014594:Uterine Neoplasms / Q000473:pathology
chemical_list: C492314:GRN protein, human; D036341:Intercellular Signaling Peptides and Proteins; D000077153:Progranulins; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D053181:Caspase 8