Linked Life Data

11466381

Source:http://linkedlifedata.com/resource/pubmed/id/11466381

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2001-7-23
pubmed:abstractText
NF-kappaB binding sites are present in the promoter regions of many acute phase and inflammatory response genes, suggesting that NF-kappaB plays an important role in the initiation of innate immune responses. However, targeted mutations of the various NF-kappaB family members have yet to identify members responsible for this critical role. RelA-deficient mice die on embryonic day 15 from TNF-alpha-induced liver degeneration. To investigate the importance of RelA in innate immunity, we genetically suppressed this embryonic lethality by breeding the RelA deficiency onto a TNFR type 1 (TNFR1)-deficient background. TNFR1/RelA-deficient mice were born healthy, but were susceptible to bacterial infections and bacteremia and died within a few weeks after birth. Hemopoiesis was intact in TNFR1/RelA-deficient newborns, but neutrophil emigration to alveoli during LPS-induced pneumonia was severely reduced relative to that in wild-type or TNFR1-deficient mice. In contrast, radiation chimeras reconstituted with RelA or TNFR1/RelA-deficient hemopoietic cells were healthy and demonstrated no defect in neutrophil emigration during LPS-induced pneumonia. Analysis of RNA harvested from the lungs of mice 4 h after LPS insufflation revealed that the induction of several genes important for neutrophil recruitment to the lung was significantly reduced in TNFR1/RelA-deficient mice relative to that in wild-type or TNFR1-deficient mice. These results suggest that TNFR1-independent activation of RelA is essential in cells of nonhemopoietic origin during the initiation of an innate immune response.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0022-1767
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
167
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1592-600
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:11466381-Animals, pubmed-meshheading:11466381-Antigens, CD, pubmed-meshheading:11466381-Female, pubmed-meshheading:11466381-Fetal Death, pubmed-meshheading:11466381-Gene Deletion, pubmed-meshheading:11466381-Gene Expression Regulation, pubmed-meshheading:11466381-Gene Targeting, pubmed-meshheading:11466381-Hematopoiesis, pubmed-meshheading:11466381-Lipopolysaccharides, pubmed-meshheading:11466381-Male, pubmed-meshheading:11466381-Mice, pubmed-meshheading:11466381-Mice, Inbred C57BL, pubmed-meshheading:11466381-Mice, Knockout, pubmed-meshheading:11466381-NF-kappa B, pubmed-meshheading:11466381-Neutrophil Infiltration, pubmed-meshheading:11466381-Peritonitis, pubmed-meshheading:11466381-Pneumonia, Bacterial, pubmed-meshheading:11466381-Radiation Chimera, pubmed-meshheading:11466381-Receptors, Tumor Necrosis Factor, pubmed-meshheading:11466381-Receptors, Tumor Necrosis Factor, Type I, pubmed-meshheading:11466381-Survival Analysis, pubmed-meshheading:11466381-Thioglycolates, pubmed-meshheading:11466381-Transcription Factor RelA
pubmed:year
2001
pubmed:articleTitle
Targeted mutation of TNF receptor I rescues the RelA-deficient mouse and reveals a critical role for NF-kappa B in leukocyte recruitment.
pubmed:affiliation
Center for Cancer Research and Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't