ArticleJournal of inflammation (London, England)2015
The PPAR-γ antagonist GW9662 elicits differentiation of M2c-like cells and upregulation of the MerTK/Gas6 axis: a key role for PPAR-γ in human macrophage polarization.
Article in Journal of inflammation (London, England), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
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Who cites it
56 citing papers in PubMed, 115 citations in OpenAlex.
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- The impact of aspirin on PD-L1 expression and alteration of M2 polarization in non-small cell lung cancer.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2025Article
- Electroacupuncture improves cardiac function in hyperlipidemic rats by enhancing efferocytosis in myocardial macrophages via the PPARγ-LXRα-MerTK pathway.Journal of traditional and complementary medicine · 2025Article
- Gpr109A in TAMs promoted hepatocellular carcinoma via increasing PKA/PPARγ/MerTK/IL-10/TGFβ induced M2c polarization.Scientific reports · 2025Article
- The Sensitive Genes for Cervical Cancer: Two-Sample Mendelian Randomization with Experimental Validation.International journal of women's health · 2025Article
- Immunocyte lipid metabolic reprogramming: a novel pathway for targeted intervention in autoimmune diseases.Frontiers in immunology · 2025Review
- Macrophages: their role in immunity and their relationship with fatty acids in health and disease.Frontiers in immunology · 2025Review
- Macrophage polarization and macrophage-related factor expression in hypertrophy of the ligamentum flavum.European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society · 2024Article
- Interplay between Senescence and Macrophages in Diabetic Cardiomyopathy: A Review of the Potential Role of GDF-15 and Klotho.Biomedicines · 2024Review
- The Symbiosis Between Lactobacillus acidophilus and Inulin: Metabolic Benefits in an Obese Murine Model.Probiotics and antimicrobial proteins · 2024Article
- Immunomodulatory effects of curcumin on macrophage polarization in rheumatoid arthritis.Frontiers in pharmacology · 2024Review
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- Sitosterol-rich3 Biotech · 2023Article
- Impact of Lipid Metabolism on Macrophage Polarization: Implications for Inflammation and Tumor Immunity.International journal of molecular sciences · 2023Review
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
backgroundThe nuclear receptors PPAR-γ and LXRs regulate macrophage lipid metabolism and macrophage mediated inflammation. We examined the influence of these molecules on macrophage alternative activation, with particular focus on differentiation of "M2c" anti-inflammatory cells.
methodsWe cultured human monocytes in M0, M1, M2a or M2c macrophage differentiating conditions, in the presence or absence of PPAR-γ and LXR ligands. Flow cytometry was used to analyze membrane expression of phenotypic markers. Basal and LPS-stimulated production of soluble mediators was measured by ELISA. Efferocytosis assays were performed by coincubating monocytes/macrophages with apoptotic neutrophils.
resultsWe found that PPAR-γ inhibition, using the PPAR-γ antagonist GW9662, elicits differentiation of M2c-like (CD206(+) CD163(+) CD16(+)) cells and upregulation of the MerTK/Gas6 axis. Exposure of differentiating macrophages to IFN-γ, GM-CSF or LPS (M1 conditions), however, hampers GW9662 induction of MerTK and Gas6. When macrophages are differentiated with IL-4 (M2a conditions), addition of GW9662 results into an M2a (CD206(+) CD209(+) CD163(-) MerTK(-)) to M2c (CD206(high) CD209(-) CD163(+) MerTK(+)) polarization shift. Conversely, in the presence of dexamethasone (M2c conditions), the PPAR-γ agonist rosiglitazone attenuates CD163 and MerTK upregulation. The LXR agonist T0901317 induces MerTK independently of M2c polarization; indeed, CD206, CD163 and CD16 are downregulated. GW9662-differentiated M2c-like cells secrete high levels of Gas6 and low amounts of TNF-α and IL-10, mimicking dexamethasone effects in vitro. However, unlike conventional M2c cells, GW9662-differentiated cells do not show enhanced efferocytic ability.
conclusionsOur results provide new insights into the role of PPAR-γ and LXR receptors in human macrophage activation and reveal the existence of different patterns regulating MerTK expression. Unexpectedly, PPAR-γ appears to negatively control the expansion of a discrete subset of M2c-like anti-inflammatory macrophages.
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