Commensal anaerobic gut bacteria attenuate inflammation by regulating nuclear-cytoplasmic shuttling of PPAR-gamma and RelA

Denise Kelly, Jamie I. Campbell, T P King, George Grant, E A Jansson, Alistair George P Coutts, S Pettersson, S Conway

Research output: Contribution to journalArticle

755 Citations (Scopus)

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 PPARgamma-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.

Original languageEnglish
Pages (from-to)104-112
Number of pages9
JournalNature Immunology
Volume5
DOIs
Publication statusPublished - 2003

Keywords

  • NF-KAPPA-B
  • ACTIVATED RECEPTOR-GAMMA
  • INTESTINAL EPITHELIAL-CELLS
  • IMMUNE-RESPONSES
  • GENE-EXPRESSION
  • MAMMALIAN-CELLS
  • BOWEL-DISEASE
  • ALPHA
  • ACETYLATION
  • INHIBITION

Cite this

Kelly, D., Campbell, J. I., King, T. P., Grant, G., Jansson, E. A., Coutts, A. G. P., ... Conway, S. (2003). Commensal anaerobic gut bacteria attenuate inflammation by regulating nuclear-cytoplasmic shuttling of PPAR-gamma and RelA. Nature Immunology, 5, 104-112. https://doi.org/10.1038/ni1018

Commensal anaerobic gut bacteria attenuate inflammation by regulating nuclear-cytoplasmic shuttling of PPAR-gamma and RelA. / Kelly, Denise; Campbell, Jamie I.; King, T P ; Grant, George; Jansson, E A ; Coutts, Alistair George P; Pettersson, S ; Conway, S .

In: Nature Immunology, Vol. 5, 2003, p. 104-112.

Research output: Contribution to journalArticle

Kelly, D, Campbell, JI, King, TP, Grant, G, Jansson, EA, Coutts, AGP, Pettersson, S & Conway, S 2003, 'Commensal anaerobic gut bacteria attenuate inflammation by regulating nuclear-cytoplasmic shuttling of PPAR-gamma and RelA', Nature Immunology, vol. 5, pp. 104-112. https://doi.org/10.1038/ni1018
Kelly, Denise ; Campbell, Jamie I. ; King, T P ; Grant, George ; Jansson, E A ; Coutts, Alistair George P ; Pettersson, S ; Conway, S . / Commensal anaerobic gut bacteria attenuate inflammation by regulating nuclear-cytoplasmic shuttling of PPAR-gamma and RelA. In: Nature Immunology. 2003 ; Vol. 5. pp. 104-112.
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AB - 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 PPARgamma-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.

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KW - INTESTINAL EPITHELIAL-CELLS

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KW - BOWEL-DISEASE

KW - ALPHA

KW - ACETYLATION

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