Clinical-liver, pancreas, and biliary tractToll-like receptor 9 signaling mediates the anti-inflammatory effects of probiotics in murine experimental colitis☆
Section snippets
Animals
Balb/c, C57Bl/6 (B6), 129XB6F2, congenic mice bearing the C3H-Tlr4Lps-d mutation (i.e., resistant to LPS) on the Balb/c background, and IL-10-deficient mice were purchased from The Jackson Laboratory (Bar Harbor, ME). MyD88 (B6), TLR2 (B6), and TLR9 (129XB6F2)-deficient mice were used as described14, 15 and are currently bred in the UCSD vivarium.
Probiotic preparations
Probiotic bacteria (VSL-3) were purchased from VSL Pharmaceutical Inc. (Gaithersburg, MA). Each packet contains viable lyophilized gram+ bacteria of 4
Probiotic and E. coli DNA have immunostimulatory activities
To evaluate the immunostimulatory properties of probiotic DNA, we assessed the ability of probiotic DNA to activate NF-κB and JNK, 2 major signaling pathways involved in TLR activation.14 Probiotic DNA, but not methylated probiotic DNA or calf thymus DNA, activated NF-κB (EMSA), as did ISS-ODN but not control-ODN (Figure 1A). Similar results were obtained for JNK activation (Figure 1B). The activation of these signaling pathways resulted in the induction of IL-12 (p40) and IL-6, which was
Discussion
Persuasive evidence indicates that intestinal microflora play an important role in the initiation and the perpetuation of murine experimental colitis19 and human IBD.5 This fact initially provided the rationale for the use of probiotics to manipulate the intestinal microenvironment. In fact, recent studies have demonstrated the therapeutic effects of probiotics in various models of experimental colitis and in several clinical trials in patients with IBD or related disorders.10 However, the
Acknowledgements
The authors thank L. Beck and J. Uhle for their helpful editorial assistance.
References (23)
Inflammatory bowel diseaseimmunodiagnostics, immunotherapeutics, and ecotherapeutics
Gastroenterology
(2001)- et al.
Probiotic bacteria enhance murine and human intestinal epithelial barrier function
Gastroenterology
(2001) - et al.
Oral bacteriotherapy as maintenance treatment in patients with chronic pouchitisa double-blind, placebo-controlled trial
Gastroenterology
(2000) - et al.
Immunostimulatory DNA ameliorates experimental and spontaneous murine colitis
Gastroenterology
(2002) - et al.
Antigonococcal activity of 11 drugs used for therapy or prophylaxis of malaria
Diagn Microbiol Infect Dis
(1995) - et al.
Nutritional impact of pre- and probiotics as protective gastrointestinal organisms
Annu Rev Nutr
(2002) - et al.
Probioticsan overview of beneficial effects
Antonie Van Leeuwenhoek
(2002) - et al.
Commensal host-bacterial relationships in the gut
Science
(2001) Inflammatory bowel disease
N Engl J Med
(2002)- et al.
Lactobacillus plantarum 299V in the treatment and prevention of spontaneous colitis in interleukin-10-deficient mice
Inflamm Bowel Dis
(2002)
Probiotic impact on microbial flora, inflammation and tumour development in IL-10 knockout mice
Aliment Pharmacol Ther
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Supported in part by NIH Grants AI-40682 and DK-35108 (to E.R.) and by the Broad Medical Research Program of the Eli and Edythe L. Broad Foundation (to D.R.).