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

Article Details

Citation

Copy to clipboard

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

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

Int J Colorectal Dis. 2007 Mar;22(3):303-12. Epub 2006 May 20.

PubMed ID

16715250 [ View in PubMed

]

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.

DrugBank Data that Cites this Article

Drugs

Rivanicline

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Rivanicline	Interleukin-8	Protein	Humans	Unknown	Antagonist	Details