Evidence map›Paper›PMID 23485819›Full record

ArticleJournal of innate immunity2013

G-protein-coupled receptor kinase-5 mediates inflammation but does not regulate cellular infiltration or bacterial load in a polymicrobial sepsis model in mice.

Nandakumar Packiriswamy, Taehyung Lee, Pongali B Raghavendra, Haritha Durairaj, Hongbing Wang, Narayanan Parameswaran

Open access · bronzeAbstract read
In one paragraph

Article in Journal of innate immunity, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
1.6field-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

22 citing papers in PubMed, 29 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. The GRKs Reactome: Role in Cell Biology and Pathology.International journal of molecular sciences · 2021
    Review
  5. Review
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Review
  12. Article
  13. Proinflammatory Cytokines Mediate GPCR Dysfunction.Journal of cardiovascular pharmacology · 2017
    Review
  14. Review
  15. Article
  16. Review
  17. Review
  18. Article
  19. Article
  20. Regulation of macrophage biology by lithium: a new look at an old drug.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2014
    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

6 authors at 1 institution in 1 country.

Nandakumar PackiriswamyDivision of Human Pathology, Department of Physiology, Michigan State University, East Lansing, MI 48824, USA.
Taehyung Lee
Pongali B Raghavendra
Haritha Durairaj
Hongbing Wang
Narayanan Parameswaran
Michigan State University · US

Funding

GPCR Kinase-2 in TNFalpha Signaling in MacrophagesR01HL095637 · NHLBI · MICHIGAN STATE UNIVERSITY · PI PARAMESWARAN, NARAYANAN · 2009 to 2013
$1.8M
Arrestins in TLR4 Signaling in MacrophagesR01AR056680 · NIAMS · MICHIGAN STATE UNIVERSITY · PI PARAMESWARAN, NARAYANAN · 2009 to 2013
$1.4M
Novel GPCR Kinase Interactions in Macrophages and Role in ArthritisR21AR055726 · NIAMS · MICHIGAN STATE UNIVERSITY · PI PARAMESWARAN, NARAYANAN · 2008 to 2009
$359k
NHLBI NIH HHS HL095637NHLBI NIH HHS R01 HL095637NIAMS NIH HHS AR055726NIAMS NIH HHS AR056680NIAMS NIH HHS R01 AR056680NIAMS NIH HHS R21 AR055726
6 · The paper itself

Abstract

NFκB-dependent signaling is an important modulator of inflammation in several diseases including sepsis. G-protein-coupled receptor kinase-5 (GRK5) is an evolutionarily conserved regulator of the NFκB pathway. We hypothesized that GRK5 via NFκB regulation plays an important role in the pathogenesis of sepsis. To test this we utilized a clinically relevant polymicrobial sepsis model in mice that were deficient in GRK5. We subjected wild-type (WT) and GRK5 knockout (KO) mice to cecal ligation and puncture (CLP)-induced polymicrobial sepsis and assessed the various events in sepsis pathogenesis. CLP induced a significant inflammatory response in the WT and this was markedly attenuated in the KO mice. To determine the signaling mechanisms and the role of NFκB activation in sepsis-induced inflammation, we assessed the levels of IκBα phosphorylation and expression of NFκB-dependent genes in the liver in the two genotypes. Both IκBα phosphorylation and gene expression were significantly inhibited in the GRK5 KO compared to the WT mice. Interestingly, however, GRK5 did not modulate either immune cell infiltration (to the primary site of infection) or local/systemic bacterial load subsequent to sepsis induction. In contrast GRK5 deficiency significantly inhibited sepsis-induced plasma corticosterone levels and the consequent thymocyte apoptosis in vivo. Associated with these outcomes, CLP-induced mortality was significantly prevented in the GRK5 KO mice in the presence of antibiotics. Together, our studies demonstrate that GRK5 is an important regulator of inflammation and thymic apoptosis in polymicrobial sepsis and implicate GRK5 as a potential molecular target in sepsis.

Indexed as

AnimalsApoptosisBacterial LoadCecumCell MovementCells, CulturedCorticosteroneDisease Models, AnimalGene Expression RegulationG-Protein-Coupled Receptor Kinase 5HumansInflammationLiverMaleMiceMice, KnockoutCorticosteroneG-Protein-Coupled Receptor Kinase 5NF-kappa B

Identifiers

PMID23485819
PMCPMC3753665
OpenAlexW2031775245

What OpenQuestion holds

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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.