Linked Life Data

7516328

Source:http://linkedlifedata.com/resource/pubmed/id/7516328

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
25
pubmed:dateCreated
1994-7-20
pubmed:abstractText
Stimulation of the human monocytic cell line Mono Mac 6 with lipopolysaccharide (LPS) leads to rapid and transient expression of cytokines like tumor necrosis factor (TNF). When such cells are precultured for 2 days with a low dose of LPS (20 ng/ml) followed by stimulation with a high dose of LPS (1 microgram/ml), expression of the TNF gene is minimal, i.e. the cells are tolerant. In nuclear run-on analysis, such tolerant cells show only a low degree of transcription, indicating that tolerance operates at or upstream of the transcription level. The CD14 LPS receptor is, however, up-regulated (not down-regulated) in tolerant cells, and LPS can, in fact, still lead to activation of tolerant cells as evidenced by mobilization of the transcription factor nuclear factor kappa B (NF-kappa B). Resolution of the NF-kappa B complex in gel shift analysis shows that the binding protein, mobilized in naive Mono Mac 6 cells, consists mainly of p50-p65 heterodimers, while in tolerant cells, the p50 homodimer is predominant. This increase in p50 homodimers coincides with an increase in p105 mRNA, suggestive of a transcriptional up-regulation of p50. Reporter gene analysis reveals that the NF-kappa B complex mobilized in tolerant cells is functionally inactive in that NF-kappa B-dependent luciferase constructs containing the human immunodeficiency virus long terminal repeat or the TNF 5'-region show only minimal transactivation after LPS stimulation. Similar to Mono Mac 6 cells, primary blood monocytes, when precultured with a low dose of LPS, also become tolerant and produce little TNF after LPS stimulation. The tolerant blood monocytes also up-regulate CD14, and they mobilize NF-kappa B with a predominance of p50 homodimers. Taken together, these results demonstrate that tolerance to LPS is determined by post-receptor mechanisms that involve an altered composition of the NF-kappa B complex.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
24
pubmed:volume
269
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
17001-4
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:7516328-Antigens, CD, pubmed-meshheading:7516328-Antigens, CD14, pubmed-meshheading:7516328-Antigens, Differentiation, Myelomonocytic, pubmed-meshheading:7516328-Base Sequence, pubmed-meshheading:7516328-Cells, Cultured, pubmed-meshheading:7516328-DNA Primers, pubmed-meshheading:7516328-Drug Tolerance, pubmed-meshheading:7516328-Gene Expression Regulation, pubmed-meshheading:7516328-Humans, pubmed-meshheading:7516328-Lipopolysaccharides, pubmed-meshheading:7516328-Molecular Sequence Data, pubmed-meshheading:7516328-Molecular Weight, pubmed-meshheading:7516328-Monocytes, pubmed-meshheading:7516328-NF-kappa B, pubmed-meshheading:7516328-RNA, Messenger, pubmed-meshheading:7516328-Signal Transduction, pubmed-meshheading:7516328-Tumor Necrosis Factor-alpha, pubmed-meshheading:7516328-Up-Regulation
pubmed:year
1994
pubmed:articleTitle
Tolerance to lipopolysaccharide involves mobilization of nuclear factor kappa B with predominance of p50 homodimers.
pubmed:affiliation
Institute for Immunology, München, Federal Republic of Germany.
pubmed:publicationType
Journal Article, In Vitro, Research Support, Non-U.S. Gov't