Commensal anaerobic gut bacteria attenuate inflammation by regulating nuclear-cytoplasmic shuttling of PPAR-gamma and RelA
- PMID: 14691478
- DOI: 10.1038/ni1018
Commensal anaerobic gut bacteria attenuate inflammation by regulating nuclear-cytoplasmic shuttling of PPAR-gamma and RelA
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-kappaB. Bacteroides thetaiotaomicron targets transcriptionally active NF-kappaB subunit RelA, enhancing its nuclear export through a mechanism independent of nuclear export receptor Crm-1. Peroxisome proliferator activated receptor-gamma (PPAR-gamma), in complex with nuclear RelA, also undergoes nucleocytoplasmic redistribution in response to B. thetaiotaomicron. A decrease in PPAR-gamma abolishes both the nuclear export of RelA and the anti-inflammatory activity of B. thetaiotaomicron. This PPAR-gamma-dependent anti-inflammatory mechanism defines new cellular targets for therapeutic drug design and interventions for the treatment of chronic inflammation.
Comment in
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ComPPARtmentalizing NF-kappaB in the gut.Nat Immunol. 2004 Jan;5(1):14-6. doi: 10.1038/ni0104-14. Nat Immunol. 2004. PMID: 14699401 No abstract available.
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