title: 15-Deoxy-Delta(12,14)-prostaglandin J2 induces IL-8 and GM-CSF in a human airway epithelial cell line (NCI-H292).
abstract: BACKGROUND
  15-Deoxy-Delta(12,14)-prostaglandin J2 (15d-PGJ2), a major prostanoid metabolized from prostaglandin D2 (PGD2), plays an important role in various biological processes including inflammatory responses. 15d-PGJ2 exerts its effects through two major receptors, chemoattractant receptor- homologous molecule expressed on Th2 cells (CRTH2) and peroxisome proliferator-activated receptor-gamma (PPARgamma). The 15d-PGJ2/PPARgamma system, in particular, regulates numerous biological processes including adipogenesis, apoptosis, and inflammation. Although our studies have shown that PGD2 (metabolic precursor of 15d-PGJ2) induces IL-8 and GM-CSF production, the role of 15d-PGJ2 (metabolite of PGD2) is unknown in human bronchial epithelial cells. In this study, we investigated the function of 15d-PGJ2 on a human airway epithelial cell line: NCI-H292.
  
  
  METHODS
  NCI-H292 cells were cultured in the presence of various stimulants. The resulting supernatants were used for ELISA analysis.
  
  
  RESULTS
  We demonstrated that 15d-PGJ2 induced production of IL-8 and GM-CSF from NCI-H292. 13,14-Dihydro-15-keto-PGD2 (DK-PGD2) (CRTH2 agonist) and troglitazone (PPARgamma agonist) failed to increase the production of these cytokines. Pretreatment with ramatroban (CRTH2 antagonist) and GW9662 (PPARgamma antagonist) did not reduce the production of these cytokines. 15d-PGJ2 activated the ERK1/2 signaling pathway in a time-dependent manner.
  
  
  CONCLUSIONS
  These data showed that 15d-PGJ2 is a potent inducer of IL-8 and GM-CSF production through ERK1/2 kinase activation, but this is independent of CRTH2 or PPARgamma activation.
authors.affiliation: Department of Dermatology, Kyushu University School of Medicine, Fukuoka, Japan.
authors.forename: Takahito
authors.initials: T
authors.lastname: Chiba
authors.forename: Shigeharu
authors.initials: S
authors.lastname: Ueki
authors.forename: Wataru
authors.initials: W
authors.lastname: Ito
authors.forename: Hikari
authors.initials: H
authors.lastname: Kato
authors.forename: Masahide
authors.initials: M
authors.lastname: Takeda
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kayaba
authors.forename: Masutaka
authors.initials: M
authors.lastname: Furue
authors.forename: Junichi
authors.initials: J
authors.lastname: Chihara
mesh_terms: D045744:Cell Line, Tumor; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism*; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism*; D015230:Prostaglandin D2 / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D020545:Respiratory Mucosa / Q000187:drug effects / Q000378:metabolism*
chemical_list: C097240:15-deoxy-delta(12,14)-prostaglandin J2; D016209:Interleukin-8; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D048049:Extracellular Signal-Regulated MAP Kinases; D015230:Prostaglandin D2