Journal article
Interleukin-10 inhibits Mycobacterium bovis bacillus Calmette-Guerin (BCG)-induced macrophage cytotoxicity against bladder cancer cells
Clinical and experimental immunology, Vol.160(3), pp.359-368
06/01/2010
DOI: 10.1111/j.1365-2249.2010.04105.x
PMCID: PMC2883106
PMID: 20148913
Abstract
P>The mechanisms underlying bacillus Calmette-Guerin (BCG) immunotherapy of bladder cancer currently remain elusive. Previously, we demonstrated that macrophages were cytotoxic to bladder cancer cells upon BCG stimulation in vitro. However, macrophages from C57BL/6 mice were less potent than those from C3H/HeN mice for the killing of bladder cancer cells. This study was to determine whether interleukin (IL)-10 produced by macrophages in response to BCG is a causative factor for the reduced cytotoxicity in BCG-stimulated C57BL/6 macrophages. Thioglycollate-elicited peritoneal macrophages were prepared and analysed for the BCG induction of cytotoxicity, cytokines and nitric oxide (NO) in vitro. Compared to BCG-stimulated C3H/HeN macrophages, BCG-stimulated C57BL/6 macrophages exhibited reduced killing of bladder cancer MBT-2 cells and MB49 cells. Studies demonstrated further that BCG-stimulated C57BL/6 macrophages produced a high level of IL-10, which correlated with reduced production of tumour necrosis factor (TNF)-alpha, IL-6 and NO. Neutralizing endogenous IL-10 during BCG stimulation increased C57BL/6 macrophage cytotoxicity against MB49 cells by 3 center dot 2-fold, along with increased production of TNF-alpha by 6 center dot 4-fold and NO by 3 center dot 6-fold, respectively. Macrophages from C57BL/6 IL-10-/- mice also exhibited increased killing of MB49 cells and production of TNF-alpha and NO upon BCG stimulation. In addition, supplementation of exogenous recombinant IL-10 reduced BCG-induced C3H/HeN macrophage cytotoxicity against both MBT-2 cells and MB49 cells in a dose-dependent manner. These results reveal the inhibitory role of IL-10 in BCG-induced macrophage cytotoxicity, suggesting that blockage of IL-10 may potentially enhance the effect of BCG in the treatment of bladder cancer patients.
Details
- Title: Subtitle
- Interleukin-10 inhibits Mycobacterium bovis bacillus Calmette-Guerin (BCG)-induced macrophage cytotoxicity against bladder cancer cells
- Creators
- Y. Luo - University of IowaR. Han - Tainjin Institute of Urology, Tainjin, ChinaD. P. Evanoff - University of IowaX. Chen - University of Iowa
- Resource Type
- Journal article
- Publication Details
- Clinical and experimental immunology, Vol.160(3), pp.359-368
- Publisher
- Wiley
- DOI
- 10.1111/j.1365-2249.2010.04105.x
- PMID
- 20148913
- PMCID
- PMC2883106
- ISSN
- 0009-9104
- eISSN
- 1365-2249
- Number of pages
- 10
- Language
- English
- Date published
- 06/01/2010
- Academic Unit
- Urology; Internal Medicine
- Record Identifier
- 9984320062902771
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