Evidence map›Paper›PMID 31263039›Full record

ArticleJournal of immunology (Baltimore, Md. : 1950)2019

Azithromycin Polarizes Macrophages to an M2 Phenotype via Inhibition of the STAT1 and NF-κB Signaling Pathways.

Dalia Haydar, Theodore J Cory, Susan E Birket, Brian S Murphy, Keith R Pennypacker, Anthony P Sinai, David J Feola

Open access · bronzeAbstract read
In one paragraph

Article in Journal of immunology (Baltimore, Md. : 1950), 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers.

0numbers the graph read from it
0cells of the map it votes in
72citing papers in PubMed
5.5field-weighted citation impact, top 3% 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

72 citing papers in PubMed, 127 citations in OpenAlex.

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  13. Characterizing the pan-cancer role of exosomal miRNAs in metastasis across cancers.Computational and structural biotechnology journal · 2025
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  19. Multifunctional Bionic Periosteum with Ion Sustained-Release for Bone Regeneration.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024
    Article
  20. Characterizing the role of exosomal miRNAs in metastasis.bioRxiv : the preprint server for biology · 2024
    Article

12 more citing papers are in PubMed but not listed here.

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

7 authors at 4 institutions in 1 country.

Dalia HaydarDepartment of Pharmacy Practice and Science, University of Kentucky College of Pharmacy, Lexington, KY 40536.ORCID 0000-0002-7959-2699
Theodore J CoryDepartment of Clinical Pharmacy and Translational Science, University of Tennessee Health Science Center, Memphis, TN 38163.ORCID 0000-0002-3350-8527
Susan E BirketDivision of Pulmonary, Allergy and Critical Care Medicine, University of Alabama-Birmingham, Birmingham, AL 35294.
Brian S MurphyMedpace, Cincinnati, OH 45227.ORCID 0000-0002-0865-3095
Keith R PennypackerDepartment of Neurology, University of Kentucky College of Medicine, Lexington, KY 40536.ORCID 0000-0002-4618-0903
Anthony P SinaiDepartment of Microbiology, Immunology and Molecular Genetics, University of Kentucky College of Medicine, Lexington, KY 40536.
David J FeolaDepartment of Pharmacy Practice and Science, University of Kentucky College of Pharmacy, Lexington, KY 40536; david.feola@uky.edu.ORCID 0000-0003-1129-2304
University of Kentucky · USMedpace (United States) · USUniversity of Alabama at Birmingham · USUniversity of Tennessee Health Science Center · US

Funding

The natural killer cell response against mouse cytomegalovirus infectionR01AI100874 · NIAID · SLOAN-KETTERING INST CAN RESEARCH · PI Joseph Chai-Yuen Sun · 2012 to 2026
$7.4M
Alternative macrophage activation in acute Pseudomonas pneumoniaR01AI095307 · NIAID · UNIVERSITY OF KENTUCKY · PI FEOLA, DAVID · 2012 to 2016
$1.8M
Natural killer cell responses against viral infectionR00AI085034 · NIAID · SLOAN-KETTERING INST CAN RESEARCH · PI SUN, JOSEPH CHAI-YUEN · 2010 to 2011
$498k
NIAID NIH HHS R00 AI085034NIAID NIH HHS R01 AI095307NIAID NIH HHS R01 AI100874
6 · The paper itself

Abstract

Azithromycin is effective at controlling exaggerated inflammation and slowing the long-term decline of lung function in patients with cystic fibrosis. We previously demonstrated that the drug shifts macrophage polarization toward an alternative, anti-inflammatory phenotype. In this study we investigated the immunomodulatory mechanism of azithromycin through its alteration of signaling via the NF-κB and STAT1 pathways. J774 murine macrophages were plated, polarized (with IFN-γ, IL-4/-13, or with azithromycin plus IFN-γ) and stimulated with LPS. The effect of azithromycin on NF-κB and STAT1 signaling mediators was assessed by Western blot, homogeneous time-resolved fluorescence assay, nuclear translocation assay, and immunofluorescence. The drug's effect on gene and protein expression of arginase was evaluated as a marker of alternative macrophage activation. Azithromycin blocked NF-κB activation by decreasing p65 nuclear translocation, although blunting the degradation of IκBα was due, at least in part, to a decrease in IKKβ kinase activity. A direct correlation was observed between increasing azithromycin concentrations and increased IKKβ protein expression. Moreover, incubation with the IKKβ inhibitor IKK16 decreased arginase expression and activity in azithromycin-treated cells but not in cells treated with IL-4 and IL-13. Importantly, azithromycin treatment also decreased STAT1 phosphorylation in a concentration-dependent manner, an effect that was reversed with IKK16 treatment. We conclude that azithromycin anti-inflammatory mechanisms involve inhibition of the STAT1 and NF-κB signaling pathways through the drug's effect on p65 nuclear translocation and IKKβ.

Indexed as

AnimalsAnti-Inflammatory AgentsAzithromycinCells, CulturedMacrophage ActivationMacrophagesMiceNF-kappa BSignal TransductionSTAT1 Transcription FactorAnti-Inflammatory AgentsAzithromycinNF-kappa BStat1 protein, mouseSTAT1 Transcription Factor

Identifiers

PMID31263039
PMCPMC6684391
OpenAlexW2955432490

What OpenQuestion 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 OpenQuestion graph.