RGD Reference Report - Effect of endotoxin on expression of TNF receptors and transport of TNF-alpha at the blood-brain barrier of the rat. - Rat Genome Database

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Effect of endotoxin on expression of TNF receptors and transport of TNF-alpha at the blood-brain barrier of the rat.

Authors: Osburg, B  Peiser, C  Domling, D  Schomburg, L  Ko, YT  Voigt, K  Bickel, U 
Citation: Osburg B, etal., Am J Physiol Endocrinol Metab 2002 Nov;283(5):E899-908.
RGD ID: 628388
Pubmed: PMID:12376316   (View Abstract at PubMed)
DOI: DOI:10.1152/ajpendo.00436.2001   (Journal Full-text)

The transport mechanism mediating brain uptake of tumor necrosis factor (TNF)-alpha has been studied. When (125)I-labeled rat TNF-alpha was used in internal carotid artery perfusions in rats, the cytokine showed transcytosis through the blood-brain barrier in intact form (permeability-surface area product 0.34 +/- 0.13 microl. min(-1). g(-1)). Uptake was inhibited by low nanomolar concentrations of unlabeled rat TNF-alpha. Human TNF-alpha, which does not interact with the p80 TNF receptor in rodents, showed no brain uptake. mRNA expression of both p60 and p80 receptors could be demonstrated in native brain microvessel preparations. These transcripts increased to 149% (p60) and 127% (p80) of control 4 h after a systemic immune stimulation (2 mg/kg bacterial endotoxin ip). Lipopolysaccharide treatment did not alter the rate of brain uptake of TNF-alpha measured between 4 and 24 h later. In conclusion, a receptor-mediated mechanism is responsible for the transcytosis of TNF-alpha. Saturable transport, requiring the p80 receptor, occurs at concentrations encountered under pathophysiological conditions and therefore constitutes a relevant mechanism of communication between the immune system and the brain.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
immune response  IDA 628388 RGD 

Molecular Function
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
tumor necrosis factor receptor activity  IDA 628388 RGD 
tumor necrosis factor receptor binding  IDA 628388 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Tnf  (tumor necrosis factor)
Tnfrsf1b  (TNF receptor superfamily member 1B)


Additional Information