Commensal anaerobic gut bacteria attenuate inflammation by regulating nuclear-cytoplasmic shuttling of PPAR-γ and RelA
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- 21 December 2003
- journal article
- research article
- Published by Springer Nature in Nature Immunology
- Vol. 5 (1) , 104-112
- https://doi.org/10.1038/ni1018
Abstract
The human gut microflora is important in regulating host inflammatory responses and in maintaining immune homeostasis. The cellular and molecular bases of these actions are unknown. Here we describe a unique anti-inflammatory mechanism, activated by nonpathogenic bacteria, that selectively antagonizes transcription factor NF-κB. Bacteroides thetaiotaomicron targets transcriptionally active NF-κB subunit RelA, enhancing its nuclear export through a mechanism independent of nuclear export receptor Crm-1. Peroxisome proliferator activated receptor-γ (PPAR-γ), in complex with nuclear RelA, also undergoes nucleocytoplasmic redistribution in response to B. thetaiotaomicron. A decrease in PPAR-γ abolishes both the nuclear export of RelA and the anti-inflammatory activity of B. thetaiotaomicron. This PPAR-γ-dependent anti-inflammatory mechanism defines new cellular targets for therapeutic drug design and interventions for the treatment of chronic inflammation.Keywords
This publication has 42 references indexed in Scilit:
- A novel PPARγ gene therapy to control inflammation associated with inflammatory bowel disease in a murine modelGastroenterology, 2003
- Cytokines suppress adipogenesis and PPAR-γ function through the TAK1/TAB1/NIK cascadeNature Cell Biology, 2003
- Constitutive Activation of Peroxisome Proliferator-activated Receptor-γ Suppresses Pro-inflammatory Adhesion Molecules in Human Vascular Endothelial CellsPublished by Elsevier ,2002
- Genomics at work: the global gene response to enteric bacteriaGut, 2001
- IκB Family Members Function by Different MechanismsJournal of Biological Chemistry, 2001
- Oxidized Low Density Lipoprotein Inhibits Interleukin-12 Production in Lipopolysaccharide-activated Mouse Macrophages via Direct Interactions between Peroxisome Proliferator-activated Receptor-γ and Nuclear Factor-κBJournal of Biological Chemistry, 2000
- NF-κB AND REL PROTEINS: Evolutionarily Conserved Mediators of Immune ResponsesAnnual Review of Immunology, 1998
- Signal transduction through NF-κBImmunology Today, 1998
- Regulatory interactions between CD45RBhigh and CD45RBlow CD4+ T cells are important for the balance between protective and pathogenic cell-mediated immunity.The Journal of Experimental Medicine, 1994
- Interleukin-10-deficient mice develop chronic enterocolitisCell, 1993