Spoettl, Tanja and Paetzel, Christine and Herfarth, Hans and Bencherif, Merouane and Schoelmerich, Juergen and Greinwald, Roland and Gatto, Gregory J. and Rogler, Gerhard (2007) (E)-metanicotine hemigalactarate (TC-2403-12) inhibits IL-8 production in cells of the inflamed mucosa. INTERNATIONAL JOURNAL OF COLORECTAL DISEASE, 22 (3). pp. 303-312. ISSN 0179-1958, 1432-1262
Full text not available from this repository. (Request a copy)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/kappa B 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-kappa B 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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | INFLAMMATORY-BOWEL-DISEASE; NICOTINIC ACETYLCHOLINE-RECEPTOR; INTESTINAL EPITHELIAL-CELLS; ULCERATIVE-COLITIS; CROHNS-DISEASE; INTERLEUKIN-8 EXPRESSION; CIGARETTE-SMOKING; CNS SELECTIVITY; RJR-2403; NONSMOKING; nicotine derivatives; ulcerative colitis; interleukin-8; mucosal inflammation; macrophages; epithelial cells |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin I |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 21 Dec 2020 13:21 |
| Last Modified: | 21 Dec 2020 13:21 |
| URI: | https://pred.uni-regensburg.de/id/eprint/33106 |
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