1. Mycobacterium bovis Bacillus Calmette-Guérin killed by extended freeze-drying reduces colitis in mice.
- Author
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Lagranderie M, Kluge C, Kiefer-Biasizzo H, Abolhassani M, Nahori MA, Fitting C, Huerre M, Bandeira A, Bercovier H, and Marchal G
- Subjects
- Animals, BCG Vaccine administration & dosage, Colitis chemically induced, Colitis immunology, Colon pathology, Dextran Sulfate, Freeze Drying, Interleukin-1 blood, Interleukin-10 metabolism, Interleukin-6 blood, Male, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, NF-kappa B metabolism, Oxazolone, PPAR gamma metabolism, Peroxidase metabolism, Transforming Growth Factor beta metabolism, Tumor Necrosis Factor-alpha blood, Weight Loss, BCG Vaccine pharmacology, Colitis prevention & control, Colon metabolism, Forkhead Transcription Factors metabolism, Mycobacterium bovis, T-Lymphocytes, Regulatory metabolism
- Abstract
Background & Aims: Mycobacterium bovis Bacillus Calmette-Guérin (BCG), killed by extended freeze-drying (EFD), induces secretion of interleukin-10 and reduces lung inflammation in a mouse model of asthma. We investigated the effects of EFD BCG in mouse models of inflammatory bowel disease., Methods: EFD BCG was administered subcutaneously to mice with colitis induced by dextran sodium sulfate (DSS), oxazolone, or adoptive transfer of CD4(+)CD45RB(high)Foxp3(-) T cells from C57Bl/6 Foxp3GFP mice to RAG2(-/-) mice., Results: EFD BCG, administered either before induction of DSS and oxazolone colitis or after development of acute or chronic DSS-induced colitis, reduced symptom scores, loss of body weight, and inflammation. Although transfer of CD4(+)CD45RB(high)Foxp3(-) cells induced colitis in RAG2(-/-) mice, administration of EFD BCG at the time of the transfer converted Foxp3(-) T cells to Foxp3(+) T cells and the mice did not develop colitis. EFD BCG protected mice from colitis via a mechanism that required expansion of T regulatory cells and production of interleukin-10 and transforming growth factor β. EFD BCG activated the retinoid X receptor (RXR)-α-peroxisome proliferator-activated receptor (PPAR)-γ heterodimer, blocked translocation of nuclear factor κB to the nucleus, and reduced colonic inflammation; it did not increase the number of colon tumors that formed in mice with chronic DSS-induced colitis., Conclusions: EFD BCG controls severe colitis in mice by expanding T regulatory cell populations and PPAR-γ and might be developed to treat patients with inflammatory bowel disease., (Copyright © 2011 AGA Institute. Published by Elsevier Inc. All rights reserved.)
- Published
- 2011
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