Evidence map›Paper›PMID 30689633›Full record

ArticlePloS one2019

TLR4-interacting SPA4 peptide improves host defense and alleviates tissue injury in a mouse model of Pseudomonas aeruginosa lung infection.

Shanjana Awasthi, Bhupinder Singh, Vijay Ramani, Jun Xie, Stanley Kosanke

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing 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

20 citing papers in PubMed, 30 citations in OpenAlex.

  1. Article
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  4. Review
  5. Article
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  8. Interaction between alveolar macrophages and epithelial cells duringFrontiers in cellular and infection microbiology · 2023
    Review
  9. Article
  10. Article
  11. Review
  12. Article
  13. Real-time visualization of phagosomal pH manipulation byFrontiers in cellular and infection microbiology · 2022
    Article
  14. Revisiting the role of pulmonary surfactant in chronic inflammatory lung diseases and environmental exposure.European respiratory review : an official journal of the European Respiratory Society · 2021
    Review
  15. Review
  16. Observational
  17. Review
  18. Article
  19. Review
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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

5 authors at 1 institution in 1 country.

Shanjana AwasthiDepartment of Pharmaceutical Sciences, University of Oklahoma Health Sciences Center (OUHSC), Oklahoma City, Oklahoma, United States of America.ORCID 0000-0003-1249-0708
Bhupinder SinghDepartment of Pharmaceutical Sciences, University of Oklahoma Health Sciences Center (OUHSC), Oklahoma City, Oklahoma, United States of America.ORCID 0000-0002-9185-7944
Vijay RamaniDepartment of Pharmaceutical Sciences, University of Oklahoma Health Sciences Center (OUHSC), Oklahoma City, Oklahoma, United States of America.
Jun XieDepartment of Pharmaceutical Sciences, University of Oklahoma Health Sciences Center (OUHSC), Oklahoma City, Oklahoma, United States of America.
Stanley KosankeDepartment of Pathology, OUHSC, Oklahoma City, Oklahoma, United States of America.
University of Oklahoma Health Sciences Center · US

Funding

ZFC3H1 Regulation of Host Defense and Influenza A Virus PathogenesisP20GM103648 · NIGMS · OKLAHOMA STATE UNIVERSITY STILLWATER · PI PATRAUCHAN, MARIANNA M. A. · 2013 to 2022
$22.3M
Surfactant protein-A regions as TLR4-immunomodulatorsR01HL136325 · NHLBI · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · PI AWASTHI, SHANJANA · 2017 to 2021
$1.8M
NHLBI NIH HHS R01 HL136325NIGMS NIH HHS P20 GM103648
6 · The paper itself

Abstract

Interaction between surfactant protein-A (SP-A) and toll-like receptor (TLR)4 plays a critical role in host defense. In this work, we studied the host defense function of SPA4 peptide (amino acids GDFRYSDGTPVNYTNWYRGE), derived from the TLR4-interacting region of SP-A, against Pseudomonas aeruginosa. We determined the binding of SPA4 peptide to live bacteria, and its direct antibacterial activity against P. aeruginosa. Pro-phagocytic and anti-inflammatory effects were investigated in JAWS II dendritic cells and primary alveolar macrophages. The biological relevance of SPA4 peptide was evaluated in a mouse model of acute lung infection induced by intratracheal challenge with P. aeruginosa. Our results demonstrate that the SPA4 peptide does not interact with or kill P. aeruginosa when cultured outside the host. The SPA4 peptide treatment induces the uptake and localization of bacteria in the phagolysosomes of immune cells. At the same time, the secreted amounts of TNF-α are significantly reduced in cell-free supernatants of SPA4 peptide-treated cells. In cells overexpressing TLR4, the TLR4-induced phagocytic response is maintained, but the levels of TLR4-stimulated TNF-α are reduced. Furthermore, our results demonstrate that the therapeutic administration of SPA4 peptide reduces bacterial burden, inflammatory cytokines and chemokines, intracellular signaling, and lactate levels, and alleviates lung edema and tissue damage in P. aeruginosa-infected mice. Together, our results suggest that the treatment with SPA4 peptide can help control the bacterial burden, inflammation, and tissue injury in a P. aeruginosa lung infection model.

Indexed as

Pseudomonas aeruginosaAnimalsBacterial LoadCells, CulturedDisease Models, AnimalFemaleInflammation MediatorsMiceMice, Inbred C57BLPeptide FragmentsPhagocytosisPhagosomesPneumonia, BacterialProtein BindingPseudomonas InfectionsPulmonary Surfactant-Associated Protein AInflammation MediatorsPeptide FragmentsPulmonary Surfactant-Associated Protein ASPA4 peptide, humanTlr4 protein, mouseToll-Like Receptor 4

Identifiers

PMID30689633
PMCPMC6349318
OpenAlexW2912682850

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.