(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. 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.

journal_name

Int J Colorectal Dis

authors

Spoettl T,Paetzel C,Herfarth H,Bencherif M,Schoelmerich J,Greinwald R,Gatto GJ,Rogler G

doi

10.1007/s00384-006-0135-4

subject

Has Abstract

pub_date

2007-03-01 00:00:00

pages

303-12

issue

3

eissn

0179-1958

issn

1432-1262

journal_volume

22

pub_type

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