Journal
PHARMACOLOGICAL RESEARCH
Volume 58, Issue 3-4, Pages 222-231Publisher
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.phrs.2008.08.006
Keywords
G alpha i2; Dextran sodium sulphate; Ex vivo cultures; Steroids; TaqMan Low-Density gene inflammatory array
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Funding
- AstraZeneca
- Swedish Medical Research Council [K2006-72X-20147-01-3]
- Swedish Cancer Society [5058-B06-02XBC]
- Edla Johansson's Foundation
- Sahlgrenska University Hospital Foundation for Clinical research [LUA-ALF]
- Royal Science and Literature Society of Gothenburg
- Angstromke Wiberg Foundation
- Borje Dahlin Foundation
- Swedish Society of Medicine
- Anna-Lisa and Bror Bjornsson Foundation
- Uppsala University Hospital Foundation for Clinical Research
- The Swedish Foundation for Strategic Research - the Mucosal Immunobiology and Vaccine Center (MIVAC)
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The aim of this study was to investigate the relevance of mouse ex vivo cultures as a first screening model for new therapeutic agents of Inflammatory Bowel Disease (IBD). Two murine models (dextran sodium sulphate (DSS)-induced colitis and G alpha i2-deficient mice) and two anti-inflammatory agents (methyl-prednisolone and the proteasome inhibitor MG132) were evaluated. The in vivo effects of methylprednisolone were assessed in both models. Ex vivo colonic tissue from both mouse models were cultured in the presence or absence of the drugs and TaqMan Low-Density arrays were used to assess the regulation of inflammatory genes before and after drug treatment. Colitis induced a similar inflammatory gene profile in both mouse models in in vivo studies and in ex vivo cultures. The differences encountered reflected the different phases of colitis in the models, e.g. innate cytokine/chemokine profile in the DSS model and T cell related markers in G alpha i2-deficient mice. After steroid treatment, a similar pattern of genes was suppressed in the two mouse models. We confirmed the suppression of inflammatory gene expression for IL-1 beta, IL-6 and iNOS in ex vivo and in vivo colons from both mouse models by quantitative RT-PCR. Importantly, the inflammatory responses in the murine ex vivo culture system reflected the in vivo response in the inflamed colonic tissue as assessed by changes in inflammatory gene expression, suggesting that the murine culture system can be used for validation of future IBD therapies. (c) 2008 Elsevier Ltd. All rights reserved.
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