Evidence map›Paper›PMID 38891035›Full record

ArticleCells2024

Effects of Akt Activator SC79 on Human M0 Macrophage Phagocytosis and Cytokine Production.

Robert J Lee, Nithin D Adappa, James N Palmer

Abstract read
In one paragraph

Article in Cells, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
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

4 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. 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.

Robert J LeeDepartment of Otorhinolaryngology-Head and Neck Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.ORCID 0000-0001-5826-6686
Nithin D AdappaDepartment of Otorhinolaryngology-Head and Neck Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
James N PalmerDepartment of Otorhinolaryngology-Head and Neck Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

Funding

UNIVERSITY OF PENNSYLVANIA CAN CTR SUPPORT GRANTP30CA016520 · NCI · UNIVERSITY OF PENNSYLVANIA · PI Robert H. Vonderheide · 1985 to 2026
$222.3M
Virus & Reservoirs CoreP30AI045008 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI Ronald G Collman · 1999 to 2026
$78.6M
Immune function of bitter taste receptors in human macrophagesR01AI167971 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI Nithin Adappa, Robert J. Lee · 2022 to 2026
$2.5M
Cystic Fibrosis Foundation LEE21G0NCI NIH HHS P30 CA016520NIAID NIH HHS P30 AI045008NIAID NIH HHS R01 AI167971NIH HHS 1R01AI167971-03A1
6 · The paper itself

Abstract

Akt is an important kinase in metabolism. Akt also phosphorylates and activates endothelial and neuronal nitric oxide (NO) synthases (eNOS and nNOS, respectively) expressed in M0 (unpolarized) macrophages. We showed that e/nNOS NO production downstream of bitter taste receptors enhances macrophage phagocytosis. In airway epithelial cells, we also showed that the activation of Akt by a small molecule (SC79) enhances NO production and increases levels of nuclear Nrf2, which reduces IL-8 transcription during concomitant stimulation with Toll-like receptor (TLR) 5 agonist flagellin. We hypothesized that SC79's production of NO in macrophages might likewise enhance phagocytosis and reduce the transcription of some pro-inflammatory cytokines. Using live cell imaging of fluorescent biosensors and indicator dyes, we found that SC79 induces Akt activation, NO production, and downstream cGMP production in primary human M0 macrophages. This was accompanied by a reduction in IL-6, IL-8, and IL-12 production during concomitant stimulation with bacterial lipopolysaccharide, an agonist of pattern recognition receptors including TLR4. Pharmacological inhibitors suggested that this effect was dependent on Akt and Nrf2. Together, these data suggest that several macrophage immune pathways are regulated by SC79 via Akt. A small-molecule Akt activator may be useful in some infection settings, warranting future in vivo studies.

Indexed as

CytokinesMacrophagesNitric OxidePhagocytosisProto-Oncogene Proteins c-aktCyclic GMPHumansLipopolysaccharidesNF-E2-Related Factor 2Cyclic GMPCytokinesLipopolysaccharidesNF-E2-Related Factor 2Nitric OxideProto-Oncogene Proteins c-aktinflammationinnate immunitylive cell imagingmonocyte-derived macrophagessignal transductionToll-like receptor

Identifiers

PMID38891035
PMCPMC11171788

What OpenQuestion holds

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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.