Evidence map›Paper›PMID 18954908›Full record

ArticleMolecular immunology2009

LPS-induced MCP-1 expression in human microvascular endothelial cells is mediated by the tyrosine kinase, Pyk2 via the p38 MAPK/NF-kappaB-dependent pathway.

Appakkudal R Anand, Ritu Bradley, Ramesh K Ganju

Open access · greenAbstract read
In one paragraph

Article in Molecular immunology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.

0numbers the graph read from it
0cells of the map it votes in
29citing papers in PubMed
1.5field-weighted citation impact, top 18% 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

29 citing papers in PubMed, 58 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Review
  5. Serratiopeptidase AttenuatesCurrent issues in molecular biology · 2023
    Article
  6. Review
  7. Article
  8. Article
  9. Article
  10. Review
  11. Vascular Endothelial Cells and Innate Immunity.Arteriosclerosis, thrombosis, and vascular biology · 2020
    Review
  12. Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. FXYD5 Protein Has a Pro-inflammatory Role in Epithelial Cells.The Journal of biological chemistry · 2016
    Article
  19. 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

3 authors at 3 institutions in 1 country.

Appakkudal R AnandDepartment of Pathology, Ohio State University Medical Center, Columbus, OH 43210, USA.
Ritu Bradley
Ramesh K Ganju
Harvard University · USThe Ohio State University · USThe Ohio State University Wexner Medical Center · US

Funding

Role of Slit in CXCR4-Mediated Breast Cancer MetastasisR01CA109527 · NCI · OHIO STATE UNIVERSITY · PI GANJU, RAMESH K. · 2005 to 2019
$2.6M
Role of Chemokine & T-Cell Receptors in HIV PathogenesisR01HL087576 · NHLBI · OHIO STATE UNIVERSITY · PI GANJU, RAMESH K. · 2006 to 2009
$1.7M
HIV-1 gp120 Mediated Chemotaxis of Blood CellsR01AI049140 · NIAID · BETH ISRAEL DEACONESS MEDICAL CENTER · PI GANJU, RAMESH K · 2001 to 2005
$1.5M
NCI NIH HHS CA109527NCI NIH HHS R01 CA109527NHLBI NIH HHS R01 HL087576NIAID NIH HHS AI49140NIAID NIH HHS R01 AI049140
6 · The paper itself

Abstract

Bacterial endotoxin (lipopolysaccharide or LPS) has potent pro-inflammatory properties and acts on many cell types including endothelial cells. Secretion of the CC chemokine, MCP-1 (CCL2) by LPS-activated endothelial cells contributes substantially to the pathogenesis of sepsis. However, the mechanism involved in LPS-induced MCP-1 production in endothelial cells is not well understood. Using human microvascular endothelial cells (HMVEC), we analyzed the involvement of the non-receptor tyrosine kinase, Pyk2, in LPS-mediated MCP-1 production. There was a marked activation of the non-receptor tyrosine kinase, Pyk2, in response to LPS. Inhibition of Pyk2 activity using a pharmacological inhibitor, Tyrphostin A9 significantly attenuated LPS-induced Pyk2 tyrosine phosphorylation, p38 MAP kinase (MAPK) activation, NF-kappaB activation, and MCP-1 expression. Furthermore, specific inactivation of Pyk2 activity by transducing microvascular endothelial cells with catalytically inactive Pyk2 mutant (AAV-Pyk2MT) or Pyk2-specific siRNA significantly blocked LPS-induced MCP-1 production. The supernatants of these LPS-stimulated cells with attenuated Pyk2 activity demonstrated decreased trans-endothelial monocyte migration in comparison to LPS-treated controls, thus confirming the inhibition of functional MCP-1 production. In summary, our data suggest a critical role for the Pyk2 mediated pathway involving p38 MAP kinase and NF-kappaB in LPS-induced MCP-1 production in human microvascular endothelial cells.

Indexed as

Cell MovementCells, CulturedChemokine CCL2Endothelial CellsEnzyme ActivationEnzyme InhibitorsFocal Adhesion Kinase 2Gene Expression RegulationHumansLipopolysaccharidesMAP Kinase Signaling SystemMonocytesMutationNF-kappa Bp38 Mitogen-Activated Protein KinasesPhosphorylationCCL2 protein, humanChemokine CCL2Enzyme InhibitorsFocal Adhesion Kinase 2LipopolysaccharidesNF-kappa Bp38 Mitogen-Activated Protein Kinasestyrphostin A9Tyrphostins

Identifiers

PMID18954908
PMCPMC2680789
OpenAlexW1996643996

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.