PMID- 19639558
OWN - NLM
STAT- MEDLINE
DCOM- 20100107
LR  - 20220321
IS  - 1536-4844 (Electronic)
IS  - 1078-0998 (Linking)
VI  - 15
IP  - 11
DP  - 2009 Nov
TI  - Balancing inflammatory, lipid, and xenobiotic signaling pathways by VSL#3, a 
      biotherapeutic agent, in the treatment of inflammatory bowel disease.
PG  - 1721-36
LID - 10.1002/ibd.20999 [doi]
AB  - BACKGROUND: The interleukin 10 knockout mouse (IL10-KO) is a model of human 
      inflammatory bowel disease (IBD) used to study host microbial interactions and 
      the action of potential therapeutics. Using Affymetrix data analysis, important 
      signaling pathways and transcription factors relevant to gut inflammation and 
      antiinflammatory probiotics were identified. METHODS: Affymetrix microarray 
      analysis on both wildtype (WT) and IL10-KO mice orally administered with and 
      without the probiotic VSL#3 was performed and the results validated by real-time 
      polymerase chain reaction (PCR), immunocytochemistry, proteomics, and 
      histopathology. Changes in metabolically active bacteria were assessed with 
      denaturing gradient gel electrophoresis (DGGE). RESULTS: Inflammation in IL10-KO 
      mice was characterized by differential regulation of inflammatory, nuclear 
      receptor, lipid, and xenobiotic signaling pathways. Probiotic intervention 
      resulted in downregulation of CXCL9 (fold change [FC] = -3.98, false discovery 
      rate [FDR] = 0.019), CXCL10 (FC = -4.83, FDR = 0.0008), CCL5 (FC = -3.47, FDR = 
      0.017), T-cell activation (Itgal [FC = -4.72, FDR = 0.00009], Itgae [FC = -2.54 
      FDR = 0.0044]) and the autophagy gene IRGM (FC = -1.94, FDR = 0.01), a recently 
      identified susceptibility gene in human IBD. Consistent with a marked reduction 
      in integrins, probiotic treatment decreased the number of CCL5+ CD3+ 
      double-positive T cells and upregulated galectin2, which triggers apoptosis of 
      activated T cells. Importantly, genes associated with lipid and PPAR signaling 
      (PPARalpha [FC = 2.36, FDR = 0.043], PPARGC1alpha [FC = 2.58, FDR = 0.016], Nr1d2 
      [FC = 3.11, FDR = 0.0067]) were also upregulated. Altered microbial diversity was 
      noted in probiotic-treated mice. CONCLUSIONS: Bioinformatics analysis revealed 
      important immune response, phagocytic and inflammatory pathways dominated by 
      elevation of T-helper cell 1 type (TH1) transcription factors in IL10-KO mice. 
      Probiotic intervention resulted in a site-specific reduction of these pathways 
      but importantly upregulated PPAR, xenobiotic, and lipid signaling genes, 
      potential antagonists of NF-kappaB inflammatory pathways.
FAU - Reiff, C
AU  - Reiff C
AD  - Rowett Institute of Nutrition and Health, Aberdeen University, Aberdeen, UK.
FAU - Delday, M
AU  - Delday M
FAU - Rucklidge, G
AU  - Rucklidge G
FAU - Reid, M
AU  - Reid M
FAU - Duncan, G
AU  - Duncan G
FAU - Wohlgemuth, S
AU  - Wohlgemuth S
FAU - Hormannsperger, G
AU  - Hormannsperger G
FAU - Loh, G
AU  - Loh G
FAU - Blaut, M
AU  - Blaut M
FAU - Collie-Duguid, E
AU  - Collie-Duguid E
FAU - Haller, D
AU  - Haller D
FAU - Kelly, D
AU  - Kelly D
LA  - eng
PT  - Journal Article
PL  - England
TA  - Inflamm Bowel Dis
JT  - Inflammatory bowel diseases
JID - 9508162
RN  - 0 (Ccl5 protein, mouse)
RN  - 0 (Chemokine CCL5)
RN  - 0 (Xenobiotics)
RN  - 130068-27-8 (Interleukin-10)
SB  - IM
MH  - Animals
MH  - Cecum/physiology
MH  - Chemokine CCL5/metabolism
MH  - Colon/physiology
MH  - Disease Models, Animal
MH  - Inflammatory Bowel Diseases/genetics/*immunology/*therapy
MH  - Interleukin-10/genetics
MH  - Lipid Metabolism/*immunology
MH  - Mice
MH  - Mice, Knockout
MH  - Oligonucleotide Array Sequence Analysis
MH  - Phagocytosis/immunology
MH  - Probiotics/*pharmacology
MH  - Proteomics
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Signal Transduction/*immunology
MH  - Streptococcus thermophilus
MH  - Xenobiotics/*pharmacology
EDAT- 2009/07/30 09:00
MHDA- 2010/01/08 06:00
CRDT- 2009/07/30 09:00
PHST- 2009/07/30 09:00 [entrez]
PHST- 2009/07/30 09:00 [pubmed]
PHST- 2010/01/08 06:00 [medline]
AID - 10.1002/ibd.20999 [doi]
PST - ppublish
SO  - Inflamm Bowel Dis. 2009 Nov;15(11):1721-36. doi: 10.1002/ibd.20999.