Evidence map›Paper›PMID 8668165›Full record

ArticleMolecular and cellular biology1996

The lipopolysaccharide-binding protein is a secretory class 1 acute-phase protein whose gene is transcriptionally activated by APRF/STAT/3 and other cytokine-inducible nuclear proteins.

R R Schumann, C J Kirschning, A Unbehaun, H P Aberle, H P Knope, N Lamping, R J Ulevitch, F Herrmann

Open access · bronzeAbstract read
In one paragraph

Article in Molecular and cellular biology, 1996. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 71 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
71citing papers in PubMed, 3 pooled it
4.0field-weighted citation impact, top 6% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

71 citing papers in PubMed, 3 syntheses or guidelines pooled it, 216 citations in OpenAlex.

  1. Pooled it
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  3. LBP rs2232618 polymorphism contributes to risk of sepsis after trauma.World journal of emergency surgery : WJES · 2018
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  17. Liver cirrhosis and immune dysfunction.International immunology · 2022
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11 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 4 institutions in 2 countries.

R R SchumannMax Delbrück Center for Molecular Medicine, Berlin, Germany.
C J Kirschning
A Unbehaun
H P Aberle
H P Knope
N Lamping
R J Ulevitch
F Herrmann
Max Delbrück Center · DEMax Planck Institute of Immunobiology and Epigenetics · DEScripps Research Institute · USUniversität Ulm · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Acute-phase reactants (APRs) are proteins synthesized in the liver following induction by interleukin-1 (IL-1), IL-6, and glucocorticoids, involving transcriptional gene activation. Lipopolysaccharide-binding protein (LBP) is a recently identified hepatic secretory protein potentially involved in the pathogenesis of sepsis, capable of binding the bacterial cell wall product endotoxin and directing it to its cellular receptor, CD14. In order to examine the transcriptional induction mechanisms by which the LBP gene is activated, we have investigated the regulation of expression of its mRNA in vitro and in vivo as well as the organization of 5' upstream regulatory DNA sequences. We show that induction of LBP expression is transcriptionally regulated and is dependent on stimulation with IL-1beta, IL-6, and dexamethasone. By definition, LBP thus has to be viewed as a class 1 acute-phase protein and represents the first APR identified which is capable of detecting pathogenic bacteria. Furthermore, cloning of the LBP promoter revealed the presence of regulatory elements, including the common APR promoter motif APRE/STAT-3 (acute-phase response element/signal transducer and activator of transcription 3). Luciferase reporter gene assays utilizing LBP promoter truncation and point mutation variants indicated that transcriptional activation of the LBP gene required a functional APRE/STAT-3 binding site downstream of the transcription start site, as well as an AP-1 and a C/EBP (CCAAT enhancer-binding protein) binding site. Gel retardation and supershift assays confirmed that upon cytokine stimulation APRF/STAT-3 binds to its recognition site, leading to strong activation of the LBP gene. Unraveling of the mechanism of transcriptional activation of the LBP gene, involving three known transcription factors, may contribute to our understanding of the acute-phase response and the pathophysiology of sepsis and septic shock.

Indexed as

Gene Expression RegulationMembrane GlycoproteinsTranscription, GeneticAcute-Phase ProteinsAnimalsBase SequenceCarcinoma, HepatocellularCarrier ProteinsCell NucleusCloning, MolecularCytokinesDexamethasoneDNA-Binding ProteinsDNA PrimersHumansInterleukin-1Acute-Phase ProteinsCarrier ProteinsCytokinesDexamethasoneDNA-Binding ProteinsDNA PrimersInterleukin-1Interleukin-6Lipopolysaccharide-Binding ProteinLuciferasesMembrane GlycoproteinsRecombinant ProteinsSTAT3 protein, humanSTAT3 Transcription FactorTrans-ActivatorsTranscription Factors

Identifiers

PMID8668165
PMCPMC231344
OpenAlexW2149615892

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.