title: The 15-deoxy-Delta12,14-prostaglandin J2 inhibits LPS-stimulated AKT and NF-kappaB activation and suppresses interleukin-6 in osteoblast-like cells MC3T3E-1.
abstract: OBJECTIVE
  Periodontitis is a chronic inflammatory disease that results in gingival inflammation and periodontal tissue destruction and is accompanied by alveolar bone resorption and eventual tooth loss. We examined the effect of 15-deoxy-Delta(12,14)-prostaglandin J(2) (15d-PGJ(2)) on periodontitis by inhibiting the production of interleukin-6 (IL-6).
  
  
  METHODS
  Osteoblast-like cells MC3T3E-1 were pretreated with 15d-PGJ(2) before being incubated with lipopolysaccharide (LPS), the effect of 15d-PGJ(2) on IL-6 production, expression and its regulatory mechanisms were studied by reverse transcription-polymerase chain reaction (RT-PCR), Western blot, electrophoretic mobility shift assay (EMSA), and confocal laser scanning microscopy study.
  
  
  RESULTS
  15d-PGJ(2) inhibits LPS-stimulated IL-6 production in a concentration-dependent manner in osteoblast-like cells MC3T3E-1, without appreciable cytotoxicity. To further examine the mechanism responsible for the inhibition of IL-6 production by 15d-PGJ(2), we examined the effect of 15d-PGJ(2) on nuclear factor-kappaB (NF-kappaB) activation and the phosphorylation of protein kinase B (Akt). 15d-PGJ(2) treatment clearly reduced the DNA binding activity of NF-kappaB in LPS-stimulated osteoblast-like cells MC3T3E-1, an effect that was mediated by inhibiting the degradation of inhibitor kappaB (IkappaB) and nuclear translocation of NF-kappaB p65 subunit. In addition, 15d-PGJ(2) attenuated the LPS-mediated Akt pathway. These effects of 15d-PGJ(2) were not abrogated by the PPARgamma antagonist, GW9662, indicating that they are PPARgamma-independent actions.
  
  
  CONCLUSIONS
  These results suggest that 15d-PGJ(2) possess a potent suppressive effect on inflammatory responses of osteoblast-like cells MC3T3E-1 via the Akt and NF-kappaB pathways independent of PPARgamma and suggest that this compound may offer some insight into the development of a new therapeutic approach to the prevention and treatment of periodontal diseases.
authors.affiliation: Department of Marine Life Science, Chosun University, Gwangju, Republic of Korea.
authors.forename: Won-Kyo
authors.initials: WK
authors.lastname: Jung
authors.forename: Ik-Su
authors.initials: IS
authors.lastname: Park
authors.forename: Sang-Jun
authors.initials: SJ
authors.lastname: Park
authors.forename: Sung Su
authors.initials: SS
authors.lastname: Yea
authors.forename: Yung Hyun
authors.initials: YH
authors.lastname: Choi
authors.forename: Sangtaek
authors.initials: S
authors.lastname: Oh
authors.forename: Sae-Gwang
authors.initials: SG
authors.lastname: Park
authors.forename: Il-Whan
authors.initials: IW
authors.lastname: Choi
mesh_terms: D016475:3T3 Cells; D000818:Animals; D015153:Blotting, Western; D002470:Cell Survival / Q000187:drug effects; D024202:Electrophoretic Mobility Shift Assay; D004797:Enzyme-Linked Immunosorbent Assay; D020672:I-kappa B Proteins / Q000037:antagonists & inhibitors; D015850:Interleukin-6 / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D051379:Mice; D018613:Microscopy, Confocal; D016328:NF-kappa B / Q000187:drug effects / Q000378:metabolism*; D051058:Oncogene Protein v-akt / Q000187:drug effects / Q000378:metabolism*; D010006:Osteoblasts / Q000187:drug effects*; D047495:PPAR gamma / Q000037:antagonists & inhibitors / Q000502:physiology; D015230:Prostaglandin D2 / Q000031:analogs & derivatives* / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014178:Translocation, Genetic / Q000187:drug effects; D000093242:Interleukin-6 Inhibitors
chemical_list: D020672:I-kappa B Proteins; D015850:Interleukin-6; D008070:Lipopolysaccharides; D016328:NF-kappa B; D051058:Oncogene Protein v-akt; D047495:PPAR gamma; D015230:Prostaglandin D2; D000093242:Interleukin-6 Inhibitors; C477819:15-deoxyprostaglandin J2