Publication Date:
2008-06-21
Description:
The control of innate immune responses through activation of the nuclear transcription factor NF-kappaB is essential for the elimination of invading microbial pathogens. We showed that the bacterial N-(3-oxo-dodecanoyl) homoserine lactone (C12) selectively impairs the regulation of NF-kappaB functions in activated mammalian cells. The consequence is specific repression of stimulus-mediated induction of NF-kappaB-responsive genes encoding inflammatory cytokines and other immune regulators. These findings uncover a strategy by which C12-producing opportunistic pathogens, such as Pseudomonas aeruginosa, attenuate the innate immune system to establish and maintain local persistent infection in humans, for example, in cystic fibrosis patients.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kravchenko, Vladimir V -- Kaufmann, Gunnar F -- Mathison, John C -- Scott, David A -- Katz, Alexander Z -- Grauer, David C -- Lehmann, Mandy -- Meijler, Michael M -- Janda, Kim D -- Ulevitch, Richard J -- New York, N.Y. -- Science. 2008 Jul 11;321(5886):259-63. doi: 10.1126/science.1156499. Epub 2008 Jun 19.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Immunology and Microbial Sciences, Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18566250" target="_blank"〉PubMed〈/a〉
Keywords:
4-Butyrolactone/*analogs & derivatives/physiology
;
Adult
;
Animals
;
Cyclic AMP Response Element-Binding Protein/metabolism
;
Cystic Fibrosis/microbiology
;
Female
;
*Gene Expression Regulation
;
Homoserine/*analogs & derivatives/physiology
;
Humans
;
I-kappa B Kinase/metabolism
;
I-kappa B Proteins/metabolism
;
Immunity, Innate
;
Interferon-gamma/immunology
;
Lipopolysaccharides/immunology
;
Macrophage Activation
;
Macrophages/*immunology/*metabolism
;
Male
;
Mice
;
Mice, Inbred C57BL
;
Mice, Transgenic
;
Middle Aged
;
NF-kappa B/*metabolism
;
Phosphorylation
;
Pseudomonas Infections/immunology/microbiology
;
Pseudomonas aeruginosa/immunology/*pathogenicity/physiology
;
*Signal Transduction
;
Toll-Like Receptors/metabolism
;
Transcription Factor RelA/metabolism
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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