Browse by author
Lookup NU author(s): Simon Dovedi, Emeritus Professor John Kirby, Dr Helen Maitland, Dr Barry Davies, John Kelly
Full text for this publication is not currently held within this repository. Alternative links are provided below where available.
Purpose: Intravesical bacillus Calmette-Guerin (BCG) therapy is the principal treatment for high risk, noninvasive urothelial carcinoma and carcinoma in situ of the bladder. However, up to 40% of patients fail to respond to this treatment. In this study the potential for inhibition of PGE 2 production by BCG treated dendritic cells (DCs) was studied in the context of preferential polarization of the immune response toward a cancer clearing T-helper type 1 immune response. Materials and Methods: Murine bone marrow derived DCs were cultured with interleukin (IL)-4 and granulocyte-macrophage colony-stimulating factor. After 7 days the cells were stimulated with BCG. Cell surface expression of co-stimulatory molecules and phagocytic ability were measured by flow cytometry analysis to verify cell activation. The production of IL-10 and IL-12 was measured after DC stimulation with BCG in the presence of IL-10, prostaglandin E2 (Cayman Chemical, Ann Arbor, Michigan), antiIL-10 antibody (Insight Biotechnology, Wembley, United Kingdom), NS-398 and indomethacin (Sigma, Poole, United Kingdom). Results: Prostaglandin E2 stimulated a dose dependent increase in the levels of IL-10 produced by BCG activated DCs (p < 0.01). IL-10 significantly decreased IL-12 production (p < 0.001), while IL-10 blockade significantly increased IL-12 levels (p < 0.05). The COX-2 selective inhibitor NS-398 caused a dose dependent increase in the concentration of IL-12 produced by BCG activated DCs (p < 0.01). This effect was also seen with the partially selective COX-1 inhibitor indomethacin (p < 0.05). Conclusions: The inhibition of PGE2 synthesis by COX inhibition favored the production of IL-12 by BCG activated DC. This potentially will result in the generation of a T-helper type 1, polarized T-cell response that may improve the efficacy of BCG therapy. Copyright © 2005 by American Urological Association.
Author(s): Dovedi SJ, Kirby JA, Atkins H, Davies BR, Kelly JD
Publication type: Article
Publication status: Published
Journal: The Journal of Urology
Year: 2005
Volume: 174
Issue: 1
Pages: 332-337
ISSN (print): 0022-5347
ISSN (electronic): 1527-3792
Publisher: Elsevier Inc.
URL: http://dx.doi.org/10.1097/01.ju.0000161589.85869.ae
DOI: 10.1097/01.ju.0000161589.85869.ae
PubMed id: 15947685
Altmetrics provided by Altmetric
