title: [Deoxycholic acid-induced signal transduction in HT-29 cells: role of NF-kappa B and interleukin-8].
abstract: OBJECTIVE
  Deoxycholic acid (DCA) has been appeared to be an endogenous colon tumor promoter. In this study, we investigated whether DCA induces nuclear factor-kappa B (NF-kappa B) activation and IL-8 expression, and tauroursodeoxycholic acid (TUDC) inhibits this signaling in HT-29 cells.
  
  
  METHODS
  After DCA treatments, time courses of NF-kappa B binding activity were determined by electrophoretic mobility shift assay (EMSA). Also, we performed Western blotting of I kappa B alpha to confirm NF-kappa B activation. Time and concentration courses of DCA-induced secretion of IL-8 were measured with ELISA in supernatants of cultured media from the cells. To evaluate the role of NF-kappa B, IL-8 levels were assessed after pretreatment with using phosphorothioate-modified anti-sense oligonucleotides (ODN). Moreover, DCA-induced secretions of IL-8 were measured after pretreatment with TUDC.
  
  
  RESULTS
  DCA dose-dependently induced prominent NF-kappa B binding complexes from 30 min to 8 hr and degradation of I kappa B alpha. The secretions of IL-8 were increased with DCA (50-200 micro M) treatment in a time and dose-dependent manner. Pre-incubation of the cells with TUDC (0.1-10 micro M) for 2 hours caused significant decreases in DCA induced IL-8 secretion. However, transient transfection using p50 or p65 AS-ODN showed no effect on IL-8 secretion.
  
  
  CONCLUSIONS
  DCA may play as a colonic tumor promoter through anti-apoptotic effect of NF-kappa B activation and IL-8 expression, and DCA-induced NF-kappa B independent IL-8 expression is inhibited by TUDC.
authors.affiliation: Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea.
authors.forename: Dong Ki
authors.initials: DK
authors.lastname: Lee
authors.forename: Sun Young
authors.initials: SY
authors.lastname: Park
authors.forename: Soon Koo
authors.initials: SK
authors.lastname: Baik
authors.forename: Sang Ok
authors.initials: SO
authors.lastname: Kwon
authors.forename: Jun Mo
authors.initials: JM
authors.lastname: Chung
authors.forename: Eok-Soo
authors.initials: ES
authors.lastname: Oh
authors.forename: Hyun Soo
authors.initials: HS
authors.lastname: Kim
mesh_terms: D015153:Blotting, Western; D003110:Colonic Neoplasms; D003840:Deoxycholic Acid / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D024202:Electrophoretic Mobility Shift Assay; D019073:HT29 Cells; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects*; D013655:Taurochenodeoxycholic Acid / Q000494:pharmacology*; D015533:Transcriptional Activation / Q000187:drug effects
chemical_list: D016209:Interleukin-8; D016328:NF-kappa B; D016376:Oligonucleotides, Antisense; D003840:Deoxycholic Acid; D013655:Taurochenodeoxycholic Acid; C031655:ursodoxicoltaurine