Evidence map›Paper›PMID 22287708›Full record

ArticleJournal of immunology (Baltimore, Md. : 1950)2012

The IKKα-dependent NF-κB p52/RelB noncanonical pathway is essential to sustain a CXCL12 autocrine loop in cells migrating in response to HMGB1.

Richard R Kew, Marianna Penzo, David M Habiel, Kenneth B Marcu

Open access · bronzeAbstract read
In one paragraph

Article in Journal of immunology (Baltimore, Md. : 1950), 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.

0numbers the graph read from it
0cells of the map it votes in
53citing papers in PubMed
5.2field-weighted citation impact, top 4% 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

53 citing papers in PubMed, 77 citations in OpenAlex.

  1. HMGB1 as a danger signal in vascular remodeling.The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2026
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  8. Association of Cytotoxic T-Lymphocyte Antigen-4 (International journal of molecular sciences · 2024
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  13. A novel CXCR4 antagonist counteracts paradoxical generation of cisplatin-induced pro-metastatic niches in lung cancer.Molecular therapy : the journal of the American Society of Gene Therapy · 2021
    Article
  14. Article
  15. Regenerative cross talk between cardiac cells and macrophages.American journal of physiology. Heart and circulatory physiology · 2021
    Article
  16. Cancer metastasis as a non-healing wound.British journal of cancer · 2021
    Review
  17. Review
  18. High COAmerican journal of respiratory cell and molecular biology · 2020
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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

4 authors at 3 institutions in 2 countries.

Richard R KewDepartment of Pathology, Stony Brook University Medical Center, Stony Brook, NY 11794, USA.
Marianna Penzo
David M Habiel
Kenneth B Marcu
Stony Brook University Hospital · USPoliclinico S.Orsola-Malpighi · ITStony Brook University · US

Funding

Mechanisms of a Novel Chemotactic Cofactor for C5aR01GM063769 · NIGMS · STATE UNIVERSITY NEW YORK STONY BROOK · PI KEW, RICHARD R · 2001 to 2011
$2.6M
MOLECULAR AND CELLULAR BIOLOGY TRAINING PROGRAMT32GM008468 · NIGMS · STATE UNIVERSITY NEW YORK STONY BROOK · PI NEIMAN, AARON M · 1997 to 2016
$1.9M
Novel roles of IKK complex to program gene expressionR01GM066882 · NIGMS · STATE UNIVERSITY NEW YORK STONY BROOK · PI MARCU, KENNETH B · 2003 to 2006
$1.3M
Mechanisms of a Novel Chemotactic Cofactor for C5aR56GM063769 · NIGMS · STATE UNIVERSITY NEW YORK STONY BROOK · PI KEW, RICHARD R · 2007 to 2007
$310k
NIGMS NIH HHS 5T32 GM008468NIGMS NIH HHS GM063769NIGMS NIH HHS GM066882NIGMS NIH HHS R01 GM063769NIGMS NIH HHS R01 GM066882NIGMS NIH HHS R56 GM063769NIGMS NIH HHS T32 GM008468
6 · The paper itself

Abstract

HMGB1 is a chromatin architectural protein that is released by dead or damaged cells at sites of tissue injury. Extracellular HMGB1 functions as a proinflammatory cytokine and chemoattractant for immune effector and progenitor cells. Previously, we have shown that the inhibitor of NF-κB kinase (IKK)β- and IKKα-dependent NF-κB signaling pathways are simultaneously required for cell migration to HMGB1. The IKKβ-dependent canonical pathway is needed to maintain expression of receptor for advanced glycation end products, the ubiquitously expressed receptor for HMGB1, but the target of the IKKα non-canonical pathway was not known. In this study, we show that the IKKα-dependent p52/RelB noncanonical pathway is critical to sustain CXCL12/SDF1 production in order for cells to migrate toward HMGB1. Using both mouse bone marrow-derived macrophages and mouse embryo fibroblasts (MEFs), it was observed that neutralization of CXCL12 by a CXCL12 mAb completely eliminated chemotaxis to HMGB1. In addition, the HMGB1 migration defect of IKKα KO and p52 KO cells could be rescued by adding recombinant CXCL12 to cells. Moreover, p52 KO MEFs stably transduced with a GFP retroviral vector that enforces physiologic expression of CXCL12 also showed near normal migration toward HMGB1. Finally, both AMD3100, a specific antagonist of CXCL12's G protein-coupled receptor CXCR4, and an anti-CXCR4 Ab blocked HMGB1 chemotactic responses. These results indicate that HMGB1-CXCL12 interplay drives cell migration toward HMGB1 by engaging receptors of both chemoattractants. This novel requirement for a second receptor-ligand pair enhances our understanding of the molecular mechanisms regulating HMGB1-dependent cell recruitment to sites of tissue injury.

Indexed as

AnimalsAutocrine CommunicationCell MovementCell Transformation, NeoplasticChemokine CXCL12HMGB1 ProteinI-kappa B KinaseMiceMice, KnockoutMice, TransgenicNF-kappa B p52 SubunitSignal TransductionTranscription Factor RelBTumor Cells, CulturedChemokine CXCL12Chuk protein, mouseHMGB1 ProteinI-kappa B KinaseNF-kappa B p52 SubunitRelb protein, mouseTranscription Factor RelB

Identifiers

PMID22287708
PMCPMC3288724
OpenAlexW2160007664

What OpenQuestion holds

Textmetadata
LicenceTDM
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.