Evidence map›Paper›PMID 38197521›Full record

ArticleInternational forum of allergy & rhinology2024

Akt activator SC79 stimulates antibacterial nitric oxide generation in human nasal epithelial cells in vitro.

Robert J Lee, Nithin D Adappa, James N Palmer

Open access · greenAbstract read
In one paragraph

Article in International forum of allergy & rhinology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
1.2field-weighted citation impact, top 26% 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

3 citing papers in PubMed, 2 citations in OpenAlex.

  1. 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

3 authors at 1 institution in 1 country.

Robert J LeeDepartment of Otorhinolaryngology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA.ORCID 0000-0001-5826-6686
Nithin D AdappaDepartment of Otorhinolaryngology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA.
James N PalmerDepartment of Otorhinolaryngology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA.
University of Pennsylvania · US

Funding

Immune function of bitter taste receptors in human macrophagesR01AI167971 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI Nithin Adappa, Robert J. Lee · 2022 to 2026
$2.5M
Bitter and sweet taste receptor physiology in airway ciliated cellsR01DC016309 · NIDCD · UNIVERSITY OF PENNSYLVANIA · PI LEE, ROBERT J. · 2018 to 2022
$2.1M
Cystic Fibrosis Foundation LEE21G0NIAID NIH HHS R01 AI167971NIDCD NIH HHS R01 DC016309NIH HHS R01AI167971NIH HHS R01DC016309
6 · The paper itself

Abstract

backgroundThe role of Akt in nasal immunity is unstudied. Akt phosphorylates and activates endothelial nitric oxide synthase (eNOS) expressed in epithelial ciliated cells. Nitric oxide (NO) production by ciliated cells can have antibacterial and antiviral effects. Increasing nasal NO may be a useful antipathogen strategy in chronic rhinosinusitis (CRS). We previously showed that small-molecule Akt activator SC79 induces nasal cell NO production and suppresses IL-8 via the transcription factor Nrf-2. We hypothesized that SC79 NO production may additionally have antibacterial effects.

methodsNO production was measured using fluorescent dye DAF-FM. We tested effects of SC79 during co-culture of Pseudomonas aeruginosa with primary nasal epithelial cells, using CFU counting and live-dead staining to quantify bacterial killing. Pharmacology determined the mechanism of SC79-induced NO production and tested dependence on Akt.

resultsSC79 induced dose-dependent, Akt-dependent NO production in nasal epithelial cells. The NO production required eNOS and Akt. The NO released into the airway surface liquid killed P. aeruginosa. No toxicity (LDH release) or inflammatory effects (IL8 transcription) were observed over 24 h.

conclusionsTogether, these data suggest multiple immune pathways are stimulated by SC79, with antipathogen effects. This in vitro pilot study suggests that a small-molecule Akt activator may have clinical utility in CRS or respiratory other infection settings, warranting future in vivo studies.

Indexed as

Epithelial CellsNasal MucosaNitric OxideProto-Oncogene Proteins c-aktPseudomonas aeruginosaAnti-Bacterial AgentsCells, CulturedHumansNitric Oxide Synthase Type IIIRhinitisAnti-Bacterial AgentsNitric OxideNitric Oxide Synthase Type IIIProto-Oncogene Proteins c-aktair–liquid interfacechronic rhinosinusitiscystic fibrosisinnate immunitylive cell imagingPseudomonas aeruginosaStaphylococcus aureus

Identifiers

PMID38197521
PMCPMC11219270
OpenAlexW4390695345

What Socratic holds

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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 Socratic graph.