A noisy paracrine signal determines the cellular NF-kappaB response to lipopolysaccharide.

TitleA noisy paracrine signal determines the cellular NF-kappaB response to lipopolysaccharide.
Publication TypeJournal Article
Year of Publication2009
AuthorsLee TK, Denny EM, Sanghvi JC, Gaston JE, Maynard ND, Hughey JJ, Covert MW
JournalSci Signal
Volume2
Issue93
Paginationra65
Date Published2009
ISSN1937-9145
KeywordsActive Transport, Cell Nucleus, Animals, Cell Survival, Cells, Cultured, Coculture Techniques, Lipopolysaccharides, Mice, Mice, Inbred C57BL, NF-kappa B, Paracrine Communication, Phenotype, Tumor Necrosis Factor-alpha
Abstract

Nearly identical cells can exhibit substantially different responses to the same stimulus. We monitored the nuclear localization dynamics of nuclear factor kappaB (NF-kappaB) in single cells stimulated with tumor necrosis factor-alpha (TNF-alpha) and lipopolysaccharide (LPS). Cells stimulated with TNF-alpha have quantitative differences in NF-kappaB nuclear localization, whereas LPS-stimulated cells can be clustered into transient or persistent responders, representing two qualitatively different groups based on the NF-kappaB response. These distinct behaviors can be linked to a secondary paracrine signal secreted at low concentrations, such that not all cells undergo a second round of NF-kappaB activation. From our single-cell data, we built a computational model that captures cell variability, as well as population behaviors. Our findings show that mammalian cells can create "noisy" environments to produce diversified responses to stimuli.

DOI10.1126/scisignal.2000599
PubMed URLhttp://www.ncbi.nlm.nih.gov/pubmed/19843957?dopt=Abstract
PMCPMC2778577
Alternate JournalSci Signal
PubMed ID19843957