Linked Life Data

7583350

Source:http://linkedlifedata.com/resource/pubmed/id/7583350

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
1995-11-30
pubmed:abstractText
Stimulation with lipopolysaccharide (LPS) will lead to the expression of a variety of genes in CD14+ monocytes/macrophages, but also in CD14- fibroblasts and endothelial cells. Upon secondary LPS stimulation, the expression of many of these genes is only minimal. This applies to several cytokines, most prominent among them tumor necrosis factor (TNF). Induction of tolerance appears to require some degree of activation in the primary exposure, as partial structures of LPS induce tolerance, as long as they are able to activate cells. Studies on the mechanism of unresponsiveness in tolerant cells show that the CD14 LPS receptor is not downregulated but may even increase in number at the cell surface. Furthermore, this receptor appears to be functional in that mobilization of the transcription factor NF-kappa B does still occur. This NF-kappa B complex is composed primarily of p50p50 homodimers, that bind to the respective DNA motif in the promoter region of many proinflammatory genes, thereby blocking transactivation. However, LPS tolerance does not lead to downregulation of all kinds of response, as some genes are even increased in expression upon secondary stimulation; these include p50 of NF-kappa B, TNF receptor type II and interleukin-10 (IL-10). These gene products are involved in the downregulation of proinflammatory cytokines and may thereby be instrumental in the unresponsiveness observed. Hence, tolerance to LPS is not a passive process that occurs in an exhausted cell; rather, it is a well-controlled active response that is orchestrated in order to prevent excessive inflammation. Important modulators of tolerance are glucocorticoids, which result in a general decrease of gene expression, and interferon-gamma (IFN-gamma), which enhances expression of proinflammatory genes. LPS tolerance does occur in some clinical settings, as in hemodialysis, in sepsis and in patients treated repeatedly with LPS or other monocyte activators. In fact, LPS tolerance may be exploited for prophylaxis of severe sepsis in patients at risk.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
1078-7852
pubmed:author
pubmed:issnType
Print
pubmed:volume
45
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
13-26
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1995
pubmed:articleTitle
Molecular mechanism in tolerance to lipopolysaccharide.
pubmed:affiliation
Institute for Immunology, University of Munich, Germany.
pubmed:publicationType
Journal Article, Review, Research Support, Non-U.S. Gov't