title: Prostaglandin E2 Induces IL-6 and IL-8 Production by the EP Receptors/Akt/NF-κB Pathways in Nasal Polyp-Derived Fibroblasts.
abstract: OBJECTIVE
  Interleukin 6 (IL-6) and IL-8 participate in the pathogenesis of chronic rhinosinusitis with nasal polyps, and their levels are increased by prostaglandin E2 (PGE2) in different cell types. The purposes of this study were to determine whether PGE2 has any effect on the increase in the levels of IL-6 and IL-8 in nasal polyp-derived fibroblasts (NPDFs) and subsequently investigate the possible mechanism of this effect.
  
  
  METHODS
  Different concentrations of PGE2 were used to stimulate NPDFs at different time intervals. NPDFs were treated with agonists and antagonists of E prostanoid (EP) receptors. To determine the signaling pathway for the expression of PGE2-induced IL-6 and IL-8, PGE2 was treated with Akt and NF-κB inhibitors in NPDFs. Reverse transcription-polymerase chain reaction for IL-6 and IL-8 mRNAs was performed. IL-6 and IL-8 levels were measured byenzyme-linked immunosorbent assay (ELISA). The activation of Akt and NF-κB was evaluated by western blot analysis.
  
  
  RESULTS
  PGE2 significantly increased the mRNA and protein expression levels of IL-6 and IL-8 in NPDFs. The EP2 and EP4 agonists and antagonists induced and inhibited IL-6 expression. However, the EP4 agonist and antagonist were only observed to induce and inhibit IL-8 expression level. The Akt and NF-κB inhibitors significantly blocked PGE2-induced expression of IL-6 and IL-8.
  
  
  CONCLUSIONS
  PGE2 increases IL-6 expression via EP2 and EP4 receptors, and IL-8 expression via the EP4 receptor in NPDFs. It also activates the Akt and NF-κB signal pathways for the production of IL-6 and IL-8 in NPDFs. These results suggest that signaling pathway for IL-6 and IL-8 expression induced by PGE2 might be a useful therapeutic target for the treatment of nasal polyposis.
authors.affiliation: Brain Korea 21 Plus for Biomedical Science, Korea University College of Medicine, Seoul, Korea. ; Institute for Medical Devices Clinical Trial Center, Guro Hospital, Korea University, Seoul, Korea.
authors.forename: Jung-Sun
authors.initials: JS
authors.lastname: Cho
authors.affiliation: Brain Korea 21 Plus for Biomedical Science, Korea University College of Medicine, Seoul, Korea.
authors.forename: In-Hye
authors.initials: IH
authors.lastname: Han
authors.affiliation: Brain Korea 21 Plus for Biomedical Science, Korea University College of Medicine, Seoul, Korea.
authors.forename: Hye Rim
authors.initials: HR
authors.lastname: Lee
authors.affiliation: Brain Korea 21 Plus for Biomedical Science, Korea University College of Medicine, Seoul, Korea. ; Institute for Medical Devices Clinical Trial Center, Guro Hospital, Korea University, Seoul, Korea. ; Department of Otorhinolaryngology-Head and Neck Surgery, College of Medicine, Korea University, Seoul, Korea.
authors.forename: Heung-Man
authors.initials: HM
authors.lastname: Lee
keywords: Akt; E prostanoid receptor; Nasal polyps; interleukin-6; interleukin-8; prostaglandins E