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

doi:10.1038/ni1018

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

The Rowett Institute of Nutrition and Health

Research output: Contribution to journal › Article › peer-review

879 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 language	English
Pages (from-to)	104-112
Number of pages	9
Journal	Nature Immunology
Volume	5
DOIs	https://doi.org/10.1038/ni1018
Publication status	Published - 2003

Keywords

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

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@article{136f5445a08347b3bdb4c8e7701a3322,

title = "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 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.",

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

author = "Denise Kelly and Campbell, {Jamie I.} and King, {T P} and George Grant and Jansson, {E A} and Coutts, {Alistair George P} and S Pettersson and S Conway",

year = "2003",

doi = "10.1038/ni1018",

language = "English",

volume = "5",

pages = "104--112",

journal = "Nature Immunology",

issn = "1529-2908",

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TY - JOUR

T1 - Commensal anaerobic gut bacteria attenuate inflammation by regulating nuclear-cytoplasmic shuttling of PPAR-gamma and RelA

AU - Kelly, Denise

AU - Campbell, Jamie I.

AU - King, T P

AU - Grant, George

AU - Jansson, E A

AU - Coutts, Alistair George P

AU - Pettersson, S

AU - Conway, S

PY - 2003

Y1 - 2003

N2 - 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.

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.

KW - NF-KAPPA-B

KW - ACTIVATED RECEPTOR-GAMMA

KW - INTESTINAL EPITHELIAL-CELLS

KW - IMMUNE-RESPONSES

KW - GENE-EXPRESSION

KW - MAMMALIAN-CELLS

KW - BOWEL-DISEASE

KW - ALPHA

KW - ACETYLATION

KW - INHIBITION

U2 - 10.1038/ni1018

DO - 10.1038/ni1018

M3 - Article

SN - 1529-2908

VL - 5

SP - 104

EP - 112

JO - Nature Immunology

JF - Nature Immunology

ER -

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

Abstract

Keywords

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