ArticleInternational immunopharmacology2023
IFIH1/IRF1/STAT1 promotes sepsis associated inflammatory lung injury via activating macrophage M1 polarization.
Article in International immunopharmacology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 59 citations in OpenAlex.
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- NHWD-870, a Potent BET Inhibitor, Ameliorated Endotoxemia-Induced Hepatic Inflammation via Suppression of BRD4-STAT1 Signaling and Macrophage M1 Polarization.Journal of inflammation research · 2026Article
- Ferroptosis suppressor protein 1-mediated ferroptosis suppression in sepsis: non-canonical antioxidant pathways, inflammatory regulation, and therapeutic perspectives.Frontiers in immunology · 2026Review
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- TGFBI Inhibits the Pyroptosis of Macrophages to Ameliorate Septic Shock.Journal of cellular and molecular medicine · 2025Article
- Endothelial-Derived CCL7 Promotes Macrophage Polarization and Aggravates Septic Acute Lung Injury via CCR1-Mediated STAT1 Succinylation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
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- Identification of crucial genes for polycystic ovary syndrome and atherosclerosis through comprehensive bioinformatics analysis and machine learning.International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics · 2025Article
- Exosomes and MicroRNAs: key modulators of macrophage polarization in sepsis pathophysiology.European journal of medical research · 2025Review
- Cytosolic nucleic acid sensing as driver of critical illness: mechanisms and advances in therapy.Signal transduction and targeted therapy · 2025Review
- The role of natural products targeting macrophage polarization in sepsis-induced lung injury.Chinese medicine · 2025Review
- Pathological and Molecular Characterization of Grass Carp Co-Infected with TwoAnimals : an open access journal from MDPI · 2025Article
- Increased pro-SFTPB in HDL promotes the pro-inflammatory transition of HDL and represents a sign of poor prognosis in ARDS patients.Journal of translational medicine · 2025Article
- Machine learning combined multi-omics analysis to explore key oxidative stress features in systemic lupus erythematosus.Frontiers in immunology · 2025Article
- Comprehensive review of macrophage models: primary cells and immortalized lines across species.Frontiers in immunology · 2025Review
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundA growing body of research has shown that the phenotypic change in macrophages from M0 to M1 is essential for the start of the inflammatory process in septic acute respiratory distress syndrome (ARDS). Potential treatment targets might be identified with more knowledge of the molecular regulation of M1 macrophages in septic ARDS.
methodsA multi-microarray interrelated analysis of high-throughput experiments from ARDS patients and macrophage polarization was conducted to identify the hub genes associated with macrophage M1 polarization and septic ARDS. Lipopolysaccharide (LPS) and Poly (I:C) were utilized to stimulate bone marrow-derived macrophages (BMDMs) for M1-polarized macrophage model construction. Knock down of the hub genes on BMDMs via shRNAs was used to screen the genes regulating macrophage M1 polarization in vitro. The cecal ligation and puncture (CLP) mouse model was constructed in knockout (KO) mice and wild-type (WT) mice to explore whether the screened genes regulate macrophage M1 polarization in septic ARDS in vivo. ChIP-seq and further experiments on BMDMs were performed to investigate the molecular mechanism.
resultsThe bioinformatics analysis of gene expression profiles from a clinical cohort of 26 ARDS patients and macrophage polarization found that the 5 hub genes (IFIH1, IRF1, STAT1, IFIT3, GBP1) may have a synergistic effect on macrophage M1 polarization in septic ARDS. Further in vivo investigations indicated that IFIH1, STAT1 and IRF1 contribute to macrophage M1 polarization. The histological evaluation and immunohistochemistry of the lungs from the IRF1
conclusionIRF1 was identified as the key molecule that regulates macrophage M1polarization and septic ARDS development in vivo and in vitro. Moreover, as the adaptor in response to infection mimics irritants, IFIH1 promotes IRF1 (transcription factor) translocation into the nucleus to initiate STAT1 transcription.
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