Evidence map›Paper›PMID 20923761›Full record

ArticleThe Journal of biological chemistry2010

Classical NF-kappaB activation negatively regulates noncanonical NF-kappaB-dependent CXCL12 expression.

Lisa A Madge, Michael J May

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.

0numbers the graph read from it
0cells of the map it votes in
34citing papers in PubMed
1.4field-weighted citation impact, top 17% 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

34 citing papers in PubMed, 56 citations in OpenAlex.

  1. Article
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  5. Review
  6. Article
  7. TNF-α Limits Serological Memory by Disrupting the Bone Marrow Niche.Journal of immunology (Baltimore, Md. : 1950) · 2023
    Article
  8. Lymph node formation and B cell homeostasis require IKK-α in distinct endothelial cell-derived compartments.Proceedings of the National Academy of Sciences of the United States of America · 2021
    Article
  9. Review
  10. High COAmerican journal of respiratory cell and molecular biology · 2020
    Article
  11. Article
  12. Article
  13. Review
  14. Review
  15. Article
  16. Review
  17. Article
  18. Article
  19. Complement membrane attack complexes activate noncanonical NF-κB by forming an Akt+ NIK+ signalosome on Rab5+ endosomes.Proceedings of the National Academy of Sciences of the United States of America · 2015
    Article
  20. Review
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

2 authors at 1 institution in 1 country.

Lisa A MadgeDepartment of Animal Biology, University of Pennsylvania School of Veterinary Medicine, Philadelphia, Pennsylvania 19104, USA.
Michael J May
University of Pennsylvania · US

Funding

Non-Canonical NF-kappaB Signaling In Endothelial CellsR01HL080612 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI MAY, MICHAEL J · 2006 to 2010
$2.0M
NHLBI NIH HHS R01 HL080612NHLBI NIH HHS R01HL080612NHLBI NIH HHS R01HL080612-04S1
6 · The paper itself

Abstract

Ligation of the lymphotoxin-β receptor (LTβR) by LIGHT (lymphotoxin-related inducible ligand that competes for glycoprotein D binding to herpes virus entry mediator on T cells (TNFSF14)) activates the noncanonical (NC) NF-κB (nuclear factor-κB) pathway and up-regulates CXCL12 gene expression by human umbilical vein endothelial cells (HUVEC). In contrast, TNF only activates classical NF-κB signaling and does not up-regulate CXCL12. To determine whether cross-talk between the classical and NC pathways affects CXCL12 expression, we investigated the effects of TNF on LIGHT signaling in HUVEC. We show here that TNF inhibits both basal and LIGHT-induced CXCL12 expression. Negative regulation by TNF requires the classical NF-κB pathway as inhibition of basal and induced CXCL12 was reversed in HUVEC-expressing dominant negative IκB (inhibitor of NF-κB) kinase (IKK)β (IKKβ(K44M)). TNF did not inhibit the NC NF-κB pathway activation as LIGHT-induced p100 processing to p52 was intact; however, TNF either alone or together with LIGHT up-regulated p100 and RelB expression and induced the nuclear localization of p100-RelB complexes. Enhanced p100 and RelB expression was inhibited by IKKβ(K44M), which led us to question whether the IκB function of elevated p100 mediates the inhibition of CXCL12 expression by TNF. We retrovirally transduced HUVEC to express p100 at a level similar to that up-regulated by TNF; however, basal and LIGHT-induced CXCL12 expression was normal in the transduced cells. In contrast, ectopic RelB expression recapitulated the effects of TNF on NC signaling and inhibited basal and LIGHT-induced CXCL12 expression by HUVEC. Our findings therefore demonstrate that TNF-induced classical NF-κB signaling up-regulates RelB expression that inhibits both basal and NC NF-κB-dependent CXCL12 expression.

Indexed as

Active Transport, Cell NucleusCell LineCell NucleusChemokine CXCL12Endothelial CellsHumansI-kappa B KinaseMutation, MissenseSignal TransductionTranscription Factor RelBTumor Necrosis Factor-alphaTumor Necrosis Factor Ligand Superfamily Member 14Umbilical VeinsUp-RegulationChemokine CXCL12CXCL12 protein, humanI-kappa B KinaseIKBKB protein, humanRELB protein, humanTNFSF14 protein, humanTranscription Factor RelBTumor Necrosis Factor-alphaTumor Necrosis Factor Ligand Superfamily Member 14

Identifiers

PMID20923761
PMCPMC2992241
OpenAlexW1983956731

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.