title: AGEs and HMGB1 Increase Inflammatory Cytokine Production from Human Placental Cells, Resulting in an Enhancement of Monocyte Migration.
abstract: OBJECTIVE
  Advanced glycation end products (AGEs) and high-mobility group box-1 (HMGB1) are considered contributing to placental inflammation. We examined the effect of AGEs and HMGB1 on cytokines from Sw.71 human trophoblast cell lines and the interactions between Sw.71 cells and THP-1-monocytes.
  
  
  METHODS
  Sw.71 cells were cultured with/without AGEs or HMGB1. We examined the role of AGEs or HMGB1 on THP1 migration and effect of AGEs on IL-6 from Sw.71 cells using co-cultures or conditioned medium from THP-1 cells.
  
  
  RESULTS
  AGEs and HMGB1 increased interleukin (IL)-6, IL-8, and chemokine C-C motif ligand 2 (CCL2) secretion from Sw.71 cells. The secretion of IL-6 was dependent on reactive oxygen species (ROS) and NF-κB. AGEs stimulated IL-6 secretion through receptor RAGE and TLR4, whereas HMGB1 stimulated it through TLR4. AGEs, but not HMGB1, increased monocyte migration via IL-8 and CCL2 from Sw.71 cells. THP-1 monocytes induced IL-6 secretion from Sw.71 cells, and AGEs further stimulated it.
  
  
  CONCLUSIONS
  AGEs and HMGB1 may promote sterile placental inflammation cooperating with monocytes/macrophages.
authors.affiliation: Laboratory of Animal Reproduction, Department of Agriculture, Tokyo University of Agriculture, Atsugi, Kanagawa, Japan.
authors.forename: Koumei
authors.initials: K
authors.lastname: Shirasuna
authors.affiliation: Laboratory of Animal Reproduction, Department of Agriculture, Tokyo University of Agriculture, Atsugi, Kanagawa, Japan.
authors.forename: Kotomi
authors.initials: K
authors.lastname: Seno
authors.affiliation: Laboratory of Animal Reproduction, Department of Agriculture, Tokyo University of Agriculture, Atsugi, Kanagawa, Japan.
authors.forename: Ayaka
authors.initials: A
authors.lastname: Ohtsu
authors.affiliation: Laboratory of Animal Reproduction, Department of Agriculture, Tokyo University of Agriculture, Atsugi, Kanagawa, Japan.
authors.forename: Shogo
authors.initials: S
authors.lastname: Shiratsuki
authors.affiliation: Department of Obstetrics and Gynecology, Jichi Medical University, Shimotsuke, Tochigi, Japan.
authors.forename: Akihide
authors.initials: A
authors.lastname: Ohkuchi
authors.affiliation: Department of Obstetrics and Gynecology, Jichi Medical University, Shimotsuke, Tochigi, Japan.
authors.forename: Hirotada
authors.initials: H
authors.lastname: Suzuki
authors.affiliation: Department of Obstetrics and Gynecology, Jichi Medical University, Shimotsuke, Tochigi, Japan.
authors.forename: Shigeki
authors.initials: S
authors.lastname: Matsubara
authors.affiliation: Department of Obstetrics and Gynecology, Jichi Medical University, Shimotsuke, Tochigi, Japan.
authors.forename: Shiho
authors.initials: S
authors.lastname: Nagayama
authors.affiliation: Laboratory of Animal Reproduction, Department of Agriculture, Tokyo University of Agriculture, Atsugi, Kanagawa, Japan.
authors.forename: Hisataka
authors.initials: H
authors.lastname: Iwata
authors.affiliation: Laboratory of Animal Reproduction, Department of Agriculture, Tokyo University of Agriculture, Atsugi, Kanagawa, Japan.
authors.forename: Takehito
authors.initials: T
authors.lastname: Kuwayama
mesh_terms: D002450:Cell Communication; D002460:Cell Line; D002465:Cell Movement; D018932:Chemokine CCL2 / Q000378:metabolism; D018920:Coculture Techniques; D005260:Female; D017127:Glycation End Products, Advanced / Q000276:immunology*; D024243:HMGB1 Protein / Q000276:immunology*; D006801:Humans; D007249:Inflammation / Q000276:immunology*; D018836:Inflammation Mediators / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D009000:Monocytes / Q000502:physiology*; D011247:Pregnancy / Q000276:immunology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D014327:Trophoblasts / Q000276:immunology*
chemical_list: D018932:Chemokine CCL2; D017127:Glycation End Products, Advanced; D024243:HMGB1 Protein; C585491:HMGB1 protein, human; D018836:Inflammation Mediators; D015850:Interleukin-6; D016209:Interleukin-8; D017382:Reactive Oxygen Species; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4
keywords: advanced glycation end products; high-mobility group box-1; inflammation; placenta