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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
Pt 16
pubmed:dateCreated
2010-8-5
pubmed:abstractText
Nuclear factor kappa B (NF-kappaB) signalling is activated by cellular stress and inflammation and regulates cytokine expression. We applied single-cell imaging to investigate dynamic responses to different doses of tumour necrosis factor alpha (TNFalpha). Lower doses activated fewer cells and those responding showed an increasingly variable delay in the initial NF-kappaB nuclear translocation and associated IkappaBalpha degradation. Robust 100 minute nuclear:cytoplasmic NF-kappaB oscillations were observed over a wide range of TNFalpha concentrations. The result is supported by computational analyses, which identified a limit cycle in the system with a stable 100 minute period over a range of stimuli, and indicated no co-operativity in the pathway activation. These results suggest that a stochastic threshold controls functional all-or-nothing responses in individual cells. Deterministic and stochastic models simulated the experimentally observed activation threshold and gave rise to new predictions about the structure of the system and open the way for better mechanistic understanding of physiological TNFalpha activation of inflammatory responses in cells and tissues.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
1477-9137
pubmed:author
pubmed:issnType
Electronic
pubmed:day
15
pubmed:volume
123
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2834-43
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
Physiological levels of TNFalpha stimulation induce stochastic dynamics of NF-kappaB responses in single living cells.
pubmed:affiliation
Centre for Cell Imaging, School of Biological Sciences, Bioscience Research Building, Liverpool, UK.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't