Back to Search
Start Over
Prophylactic systemic P2X7 receptor blockade prevents experimental colitis.
- Source :
-
BBA: Molecular Basis of Disease . Jan2014, Vol. 1842 Issue 1, p65-78. 14p. - Publication Year :
- 2014
-
Abstract
- Abstract: Background: The P2X7 receptor (P2X7-R) is a non-selective adenosine triphosphate-gated cation channel present in epithelial and immune cells, and involved in inflammatory response. Extracellular nucleotides released in conditions of cell stress or inflammation may function as a danger signal alerting the immune system from inflammation. We investigated the therapeutic action of P2X7-R blockade in a model of inflammatory bowel disease. Methods: Rats with trinitrobenzene sulfonic (TNBS) acid-induced colitis were treated with the P2X7-R antagonists A740003 or brilliant blue G (BBG) through intra-peritoneal (IP) or intra-colonic (IC) injection prior to colitis induction. Clinical and endoscopic follow-up, histological scores, myeloperoxidase activity, densities of collagen fibers and goblet cells were evaluated. P2X7-R expression, NF-kappa B and Erk activities, and densities of T-cells and macrophages were analyzed by immunoperoxidase. The inflammatory response was determined by measuring inflammatory cytokines in cultures of colon explants, by enzyme-linked immunosorbent assay. Colonic apoptosis was determined by the TUNEL assay. Results: IP-BBG significantly attenuated the severity of colitis, myeloperoxidase activity, collagen deposition, densities of lamina propria T-cells and macrophages, while maintaining goblet cell densities. IP-BBG inhibited the increase in P2X7-R expression in parallel with apoptotic rates. TNF-α and interleukin-1β stabilized in low levels, while TGF-β and interleukin-10 did not change following IP-BBG-therapy. Colonic NF-kappa-B and Erk activation were significantly lower in IP-BBG-treated animals. Prophylactic IP-A740003 also protected rats against the development of TNBS-colitis. Conclusions: Prophylactic systemic P2X7-R blockade is effective in the prevention of experimental colitis, probably due to a systemic anti-inflammatory action, interfering with a stress-inflammation amplification loop mediated by P2X7-R. [Copyright &y& Elsevier]
Details
- Language :
- English
- ISSN :
- 09254439
- Volume :
- 1842
- Issue :
- 1
- Database :
- Academic Search Index
- Journal :
- BBA: Molecular Basis of Disease
- Publication Type :
- Academic Journal
- Accession number :
- 92716599
- Full Text :
- https://doi.org/10.1016/j.bbadis.2013.10.012