title: The cyclopentenone prostaglandin PGA2 costimulates the maturation of human dendritic cells.
abstract: OBJECTIVE
  Dendritic cells (DCs), also referred to as the sentinels of the immune system, induce and coordinate important functions of immune surveillance. Prostaglandin E2 (PGE2), a member of the eicosanoid family of arachidonic acid derivatives, is widely used to enhance the TNF-alpha-driven maturation of human monocyte-derived DCs (moDCs) both in basic research and in clinical settings. However, PGE2 is known to rapidly undergo nonenzymatic dehydration to produce PGA2, a member of the cyclopentenone PGs, which have been implicated in anti-inflammatory processes.
  
  
  METHODS
  In a side-by-side analysis we therefore compared the influence of PGE2 and PGA2 on the TNF-alpha-induced maturation of human moDCs. Phenotypic changes, migratory responses towards MIP-3beta, and T-cell responses induced by the differentially matured moDCs were assessed.
  
  
  RESULTS
  We found that PGA2 is nearly as potent as PGE2 in costimulating the TNF-alpha-induced phenotypic maturation of human moDCs. Both PGE2 and PGA2 further enhanced the migratory and T-cell-stimulatory capacity of TNF-alpha-treated moDCs. Maturation of moDCs with either PGE2 or PGA2 resulted in enhanced IFN-gamma, TNF-alpha, and IL-5 production and repressed IL-10 production in allogeneic mixed leukocyte cultures. PGE2 was always more potent than PGA2.
  
  
  CONCLUSIONS
  Our data suggest that some of the effects attributed to PGE2 may in fact be mediated by its degradation product PGA2. This work also demonstrates that cyclopentenone PGs may have pro-inflammatory properties and that both PGE2 and PGA2 can contribute to the development of Th1-type immune responses.
authors.affiliation: Department of Urology & kompetenzzentrum medizin tirol (kmt), Medical University of Innsbruck, Innsbruck, Austria. martin.thurnher@uibk.ac.at
authors.forename: Martin
authors.initials: M
authors.lastname: Thurnher
authors.forename: Thomas
authors.initials: T
authors.lastname: Putz
authors.forename: Hubert
authors.initials: H
authors.lastname: Gander
authors.forename: Andrea
authors.initials: A
authors.lastname: Rahm
authors.forename: Georg
authors.initials: G
authors.lastname: Bartsch
authors.forename: Reinhold
authors.initials: R
authors.lastname: Ramoner
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology; D002478:Cells, Cultured; D002634:Chemotaxis, Leukocyte; D003713:Dendritic Cells / Q000166:cytology* / Q000187:drug effects / Q000276:immunology; D015232:Dinoprostone / Q000494:pharmacology; D005434:Flow Cytometry; D006801:Humans; D009000:Monocytes / Q000166:cytology* / Q000502:physiology; D011454:Prostaglandins A / Q000494:pharmacology*
chemical_list: D000276:Adjuvants, Immunologic; D011454:Prostaglandins A; C100008:prostaglandin A2; D015232:Dinoprostone