title: (E)-metanicotine hemigalactarate (TC-2403-12) inhibits IL-8 production in cells of the inflamed mucosa.
abstract: BACKGROUND
  Nicotine is of therapeutic value in ulcerative colitis, but its administration is connected with adverse events. Nicotine derivatives are currently being tested to maintain the therapeutic effects and minimize adverse events. TC-2403-12 is a (E)-metanicotine hemigalactarate. The aim of this study was to determine the effectiveness of TC-2403-12 in the inhibition of TNF- and lipopolysaccharide (LPS)-induced cell activation.
  
  
  METHODS
  Colonic epithelial cells (CEC), monocytes (MM6), granulocytes, and the intestinal epithelial cell line HT-29 were stimulated with TNF and LPS and treated with TC-2403-12. IL-8 secretion in the cell supernatants and NF-kappaB activation were determined by ELISA. Apoptosis was quantified by flow cytometry.
  
  
  RESULTS
  In MM6 cells, IL-8 secretion was significantly decreased to 30% of control after TC-2403-12 treatment, with best results after pretreatment for 24 h. This decrease in cell activation was not due to apoptosis and was not mediated by inhibition of NF-kappaB activation. IL-8 production in neutrophils and primary CEC also tended to be decreased after TC-2403-12 treatment. TC-2403-12 had no influence on IL-8 secretion of HT-29 cells.
  
  
  CONCLUSIONS
  TC-2403-12 effectively inhibited TNF- and LPS-induced IL-8 production in different cell types. No toxic effects occurred at the concentrations used. Preincubation of cells with TC-2403-12 showed the best effects.
authors.affiliation: Department of Internal Medicine I, University of Regensburg, 93042, Regensburg, Germany.
authors.forename: Tanja
authors.initials: T
authors.lastname: Spoettl
authors.forename: Christine
authors.initials: C
authors.lastname: Paetzel
authors.forename: Hans
authors.initials: H
authors.lastname: Herfarth
authors.forename: Merouane
authors.initials: M
authors.lastname: Bencherif
authors.forename: Juergen
authors.initials: J
authors.lastname: Schoelmerich
authors.forename: Roland
authors.initials: R
authors.lastname: Greinwald
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Gatto
authors.forename: Gerhard
authors.initials: G
authors.lastname: Rogler
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002460:Cell Line; D002478:Cells, Cultured; D003106:Colon / Q000166:cytology; D004847:Epithelial Cells / Q000187:drug effects; D006098:Granulocytes / Q000187:drug effects; D006801:Humans; D016209:Interleukin-8 / Q000096:biosynthesis*; D007413:Intestinal Mucosa / Q000187:drug effects*; D007962:Leukocytes / Q000187:drug effects*; D008070:Lipopolysaccharides / Q000494:pharmacology; D009000:Monocytes / Q000187:drug effects; D016328:NF-kappa B / Q000096:biosynthesis; D009538:Nicotine / Q000031:analogs & derivatives* / Q000494:pharmacology; D013400:Sugar Acids / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D000276:Adjuvants, Immunologic; D000893:Anti-Inflammatory Agents; D016209:Interleukin-8; D008070:Lipopolysaccharides; D016328:NF-kappa B; D013400:Sugar Acids; D014409:Tumor Necrosis Factor-alpha; C012419:metanicotine; D009538:Nicotine; C000090:galactaric acid