(E)-metanicotine hemigalactarate (TC-2403-12) inhibits IL-8 production in cells of the inflamed mucosa

Tanja Spoettl, Christine Paetzel, Hans Herfarth, Merouane Bencherif, Juergen Schoelmerich, Roland Greinwald, Gregory J. Gatto, Gerhard Rogler

Research output: Research - peer-reviewArticle

  • 6 Citations

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-κB 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-κB 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. Conclusion: 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.

LanguageEnglish (US)
Pages303-312
Number of pages10
JournalInternational Journal of Colorectal Disease
Volume22
Issue number3
DOIs
StatePublished - Mar 2007

Fingerprint

Interleukin-8
Mucous Membrane
metanicotine
Lipopolysaccharides
Epithelial Cells
Therapeutics
Nicotine
Apoptosis
HT29 Cells
Poisons
Therapeutic Uses
Ulcerative Colitis
Granulocytes
Monocytes
Flow Cytometry
Neutrophils
Enzyme-Linked Immunosorbent Assay
Cell Line

Keywords

  • Epithelial cells
  • Interleukin-8
  • Macrophages
  • Mucosal inflammation
  • Nicotine derivatives
  • Ulcerative colitis

ASJC Scopus subject areas

  • Gastroenterology

Cite this

(E)-metanicotine hemigalactarate (TC-2403-12) inhibits IL-8 production in cells of the inflamed mucosa. / Spoettl, Tanja; Paetzel, Christine; Herfarth, Hans; Bencherif, Merouane; Schoelmerich, Juergen; Greinwald, Roland; Gatto, Gregory J.; Rogler, Gerhard.

In: International Journal of Colorectal Disease, Vol. 22, No. 3, 03.2007, p. 303-312.

Research output: Research - peer-reviewArticle

Spoettl, T, Paetzel, C, Herfarth, H, Bencherif, M, Schoelmerich, J, Greinwald, R, Gatto, GJ & Rogler, G 2007, '(E)-metanicotine hemigalactarate (TC-2403-12) inhibits IL-8 production in cells of the inflamed mucosa' International Journal of Colorectal Disease, vol 22, no. 3, pp. 303-312. DOI: 10.1007/s00384-006-0135-4
Spoettl, Tanja ; Paetzel, Christine ; Herfarth, Hans ; Bencherif, Merouane ; Schoelmerich, Juergen ; Greinwald, Roland ; Gatto, Gregory J. ; Rogler, Gerhard. / (E)-metanicotine hemigalactarate (TC-2403-12) inhibits IL-8 production in cells of the inflamed mucosa. In: International Journal of Colorectal Disease. 2007 ; Vol. 22, No. 3. pp. 303-312
@article{a5b299a9fbcb4378b09f8ee2f4dc3e13,
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-κB 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-κB 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. Conclusion: 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.",
keywords = "Epithelial cells, Interleukin-8, Macrophages, Mucosal inflammation, Nicotine derivatives, Ulcerative colitis",
author = "Tanja Spoettl and Christine Paetzel and Hans Herfarth and Merouane Bencherif and Juergen Schoelmerich and Roland Greinwald and Gatto, {Gregory J.} and Gerhard Rogler",
year = "2007",
month = "3",
doi = "10.1007/s00384-006-0135-4",
volume = "22",
pages = "303--312",
journal = "International Journal of Colorectal Disease",
issn = "0179-1958",
publisher = "Springer Verlag",
number = "3",

}

TY - JOUR

T1 - (E)-metanicotine hemigalactarate (TC-2403-12) inhibits IL-8 production in cells of the inflamed mucosa

AU - Spoettl,Tanja

AU - Paetzel,Christine

AU - Herfarth,Hans

AU - Bencherif,Merouane

AU - Schoelmerich,Juergen

AU - Greinwald,Roland

AU - Gatto,Gregory J.

AU - Rogler,Gerhard

PY - 2007/3

Y1 - 2007/3

N2 - 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-κB 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-κB 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. Conclusion: 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.

AB - 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-κB 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-κB 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. Conclusion: 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.

KW - Epithelial cells

KW - Interleukin-8

KW - Macrophages

KW - Mucosal inflammation

KW - Nicotine derivatives

KW - Ulcerative colitis

UR - http://www.scopus.com/inward/record.url?scp=33846061773&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33846061773&partnerID=8YFLogxK

U2 - 10.1007/s00384-006-0135-4

DO - 10.1007/s00384-006-0135-4

M3 - Article

VL - 22

SP - 303

EP - 312

JO - International Journal of Colorectal Disease

T2 - International Journal of Colorectal Disease

JF - International Journal of Colorectal Disease

SN - 0179-1958

IS - 3

ER -