ArticleCells2021
Carbon Monoxide Regulates Macrophage Differentiation and Polarization toward the M2 Phenotype through Upregulation of Heme Oxygenase 1.
Article in Cells, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 33 citations in OpenAlex.
- Harnessing gasotransmitters for orthopaedic infection therapy: Mechanisms and advanced delivery platforms.Bioactive materials · 2027Review
- Anti-Inflammatory Effects of the Algal Diterpenoid Ruguloptone A by Modulation of M2 Response in Early Diabetic Retinopathy.Pharmaceutics · 2026Article
- HO-1-driven drug resistance in hematological malignancies: Mechanistic insights and advances in targeted therapy.iScience · 2026Review
- Iron homeostasis and macrophage polarization in oral squamous cell carcinoma: mechanisms and therapeutic perspectives.Frontiers in immunology · 2026Review
- Modulation of cellular signaling and innate immune mechanisms by cold atmospheric plasma.Frontiers in immunology · 2026Review
- Controlled Delivery of Gasotransmitters for Cardiovascular Therapy: Molecular Mechanisms, Engineered Platforms, and Translational Perspectives.International journal of nanomedicine · 2026Review
- The molecular mechanisms of gas signaling molecules in bronchopulmonary dysplasia related lung injury.Frontiers in cell and developmental biology · 2026Review
- The Mechanistic Role of PPARPPAR research · 2026Review
- Gasotransmitters bridging tumor biology and immunity: from pathophysiological insights to therapeutic potential.Frontiers in immunology · 2026Review
- Lung Ischemia-Reperfusion Injury in Lung Transplant Surgery: Where Do We Stand?Antioxidants (Basel, Switzerland) · 2025Review
- A smart CO-releasing MnSiOMaterials today. Bio · 2025Article
- Heme and immunity: The heme oxygenase dichotomy.Journal of inorganic biochemistry · 2025Review
- Carbon Monoxide Stimulates Chondrocyte Mitochondria and Protects Mitochondria During Cartilage Injury.Antioxidants (Basel, Switzerland) · 2025Article
- The Nrf Family and Its Cardioprotective Potential: Mechanisms, Functions, and Therapeutic Perspectives.Drug design, development and therapy · 2025Review
- The Neural Palette of Heme: Altered Heme Homeostasis Underlies Defective Neurotransmission, Increased Oxidative Stress, and Disease Pathogenesis.Antioxidants (Basel, Switzerland) · 2024Review
- Strategies ofFrontiers in cellular and infection microbiology · 2024Review
- Article
- The Role of Ozone as an Nrf2-Keap1-ARE Activator in the Anti-Microbial Activity and Immunity Modulation of Infected Wounds.Antioxidants (Basel, Switzerland) · 2023Article
- Carbon Monoxide-Loaded Red Blood Cell Prevents the Onset of Cisplatin-Induced Acute Kidney Injury.Antioxidants (Basel, Switzerland) · 2023Article
- Metalloporphyrins as Tools for Deciphering the Role of Heme Oxygenase in Renal Immune Injury.International journal of molecular sciences · 2023Review
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Carbon monoxide (CO) is generated by heme oxygenase (HO), and HO-1 is highly induced in monocytes and macrophages upon stimulation. Monocytes differentiate into macrophages, including pro-inflammatory (M1) and anti-inflammatory (M2) cells, in response to environmental signals. The present study investigated whether CO modulates macrophage differentiation and polarization, by applying the CO-releasing molecule-3 (CORM-3). Results showed that murine bone marrow cells are differentiated into macrophages by CORM-3 in the presence of macrophage colony-stimulating factor. CORM-3 increases expressions of macrophage markers, including F4/80 and CD11b, and alters the cell morphology into elongated spindle-shaped cells, which is a typical morphology of M2 cells. CORM-3 upregulates the expressions of genes and molecules involved in M2 polarization and M2 phenotype markers, such as STAT6, PPARγ, Ym1, Fizz1, arginase-1, and IL-10. However, exposure to CORM-3 inhibits the iNOS expression, suggesting that CO enhances macrophage differentiation and polarization toward M2. Increased HO-1 expression is observed in differentiated macrophages, and CORM-3 further increases this expression. Hemin, an HO-1 inducer, results in increased macrophage differentiation, whereas the HO-1 inhibitor zinc protoporphyrin IX inhibits differentiation. In addition, CORM-3 increases the proportion of macrophages in peritoneal exudate cells and enhances the expression of HO-1 and arginase-1 but inhibits iNOS. Taken together, these results suggest that the abundantly produced CO in activated macrophages enhances proliferation, differentiation, and polarization toward M2. It will probably help clear apoptotic cells, resolve inflammation, and promote wound healing and tissue remodeling.
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Registered trials
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