Adenosine kinase inhibitor GP515 improves experimental colitis in mice.

Details

Serval ID
serval:BIB_1262003532C8
Type
Article: article from journal or magazin.
Collection
Publications
Title
Adenosine kinase inhibitor GP515 improves experimental colitis in mice.
Journal
Journal of Pharmacology and Experimental Therapeutics
Author(s)
Siegmund B., Rieder F., Albrich S., Wolf K., Bidlingmaier C., Firestein G.S., Boyle D., Lehr H.A., Loher F., Hartmann G., Endres S., Eigler A.
ISSN
0022-3565 (Print)
ISSN-L
0022-3565
Publication state
Published
Issued date
2001
Volume
296
Number
1
Pages
99-105
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov'tPublication Status: ppublish
Abstract
Adenosine is a potent anti-inflammatory mediator. Through elevation of endogenous adenosine concentrations the adenosine kinase inhibitor GP515 might serve to down-regulate local inflammatory responses. In the present study we investigated the effect of systemic GP515 in the nonacute model of dextran sulfate sodium (DSS)-induced colitis. The clinical score, colon length, histologic score, colon cytokine production, and spleen weight from mice with DSS-induced colitis (3.5% DSS in drinking water for 11 days) receiving GP515 treatment were determined and compared with untreated control mice. Splenocytes were analyzed for phenotype, interferon-gamma (IFNgamma) production, and CD69 expression. First, GP515 treatment resulted in a significant improvement of clinical score (weight loss, stool consistency, and bleeding) and of histologic score. Second, colon shortening, an indirect parameter for the degree of inflammation, was decreased, consistent with a decreased IFNgamma concentration in the colonic tissue. Third, spleen weight was reduced in GP515-treated DSS mice. And fourth, IFNgamma synthesis and CD69 expression, as a marker for early cell activation, of ex vivo-stimulated splenocytes were suppressed in the GP515-treated DSS mice. These studies show that GP515 is effective in the therapy of DSS-induced colitis. One potential mechanism of action is the suppression of IFNgamma synthesis and CD69 expression. Adenosine kinase inhibition forms a pharmacologic target that should be further investigated for chronic inflammatory bowel disease.
Keywords
Adenosine Kinase/antagonists & inhibitors, Animals, Antigens, CD/biosynthesis, Antigens, Differentiation, T-Lymphocyte/biosynthesis, Cells, Cultured, Colitis/chemically induced, Colitis/drug therapy, Colon/metabolism, Colon/pathology, Dextran Sulfate, Enzyme Inhibitors/therapeutic use, Female, Flow Cytometry, Gastrointestinal Agents/therapeutic use, Interferon-gamma/biosynthesis, Lectins, C-Type, Mice, Mice, Inbred BALB C, Organ Size, Ribonucleosides/therapeutic use, Spleen/pathology, Tetradecanoylphorbol Acetate/pharmacology
Pubmed
Create date
26/11/2011 13:08
Last modification date
20/08/2019 12:40
Usage data