ArticleJournal of immunology (Baltimore, Md. : 1950)2019
Azithromycin Polarizes Macrophages to an M2 Phenotype via Inhibition of the STAT1 and NF-κB Signaling Pathways.
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.
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Who cites it
72 citing papers in PubMed, 127 citations in OpenAlex.
- Trial
- "The effect of 48-weeks azithromycin therapy on levels of soluble biomarkers associated with HIV-associated chronic lung disease".International immunopharmacology · 2023Trial
- A stalactite-inspired NIR/pH-responsive visualizable nano-platform for microenvironment-activated therapy of peri-implantitis-induced bone defects.Bioactive materials · 2026Article
- Azithromycin in Dentistry: From Systemic Antibiotic to a Candidate for Local Therapeutic Delivery.Pharmaceutics · 2026Review
- Dual host and pathogen targeting by MEK1/2 inhibitors.Infection and immunity · 2026Review
- Postnatal Azithromycin Is Neuroprotective and Anti-Inflammatory in a Piglet Model of Hypoxic-Ischemic Encephalopathy.Stroke · 2026Article
- Downregulation of THRB drives immune microenvironment suppression and poor outcomes, acting as a dual biomarker for clear cell renal cell carcinoma.BMC cancer · 2026Article
- Impact of clarithromycin on monocytes-macrophages in patients with coronary arterial disease: a crucial study in cardiovascular research.Molecular biology reports · 2026Article
- Systematic development and optimization of a microfluidic formulation protocol for liposomal azithromycin.RSC pharmaceutics · 2026Article
- Sputum from Individuals with Primary Ciliary Dyskinesia Drives M2-like Macrophage Polarization.Lung · 2026Article
- Design and construction of nanoengineered multifunctional microneedles with sustained-release properties for targeted microenvironment remodeling in diabetic bone regeneration.Materials today. Bio · 2025Article
- Effect of antibiotics on Kupffer cell immunometabolism relative to intracellular killing ofmBio · 2025Article
- Characterizing the pan-cancer role of exosomal miRNAs in metastasis across cancers.Computational and structural biotechnology journal · 2025Article
- Azithromycin for Preventing Bronchopulmonary Dysplasia in Extremely Preterm Infants: A Cohort Study.Pediatric pulmonology · 2025Article
- Macrophage M2 polarization induced by ANKRD22 in lung adenocarcinoma facilitates tumor angiogenesis.Central-European journal of immunology · 2025Article
- Effects of combined cyclosporin and azithromycin treatment on human mononuclear cells under lipopolysaccharide challenge.Frontiers in oral health · 2025Article
- Azithromycin-loaded PLGA microspheres coated with silk fibroin ameliorate inflammation and promote periodontal tissue regeneration.Regenerative biomaterials · 2025Article
- Enhanced infectivity of bovine viral diarrhoea virus (BVDV) in arginase-producing bovine monocyte-derived macrophages.Virulence · 2024Article
- Multifunctional Bionic Periosteum with Ion Sustained-Release for Bone Regeneration.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Characterizing the role of exosomal miRNAs in metastasis.bioRxiv : the preprint server for biology · 2024Article
12 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 1 country.
Funding
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.
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Registered trials
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.