Adiponectin Inhibits the Production of TNF-α, IL-6 and Chemokines by Human Lung Macrophages
Background: Obesity is associated with an elevated risk of severe respiratory infections and inflammatory lung diseases. The objectives were to investigate 1) the production of adiponectin by human lung explants, 2) the expression of the adiponectin receptors AdipoR1 and AdipoR2 by human lung macrop...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-08-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2021.718929/full |
| _version_ | 1819148674606825472 |
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| author | Hélène Salvator Hélène Salvator Hélène Salvator Stanislas Grassin-Delyle Stanislas Grassin-Delyle Stanislas Grassin-Delyle Marion Brollo Louis-Jean Couderc Louis-Jean Couderc Louis-Jean Couderc Charlotte Abrial Tatiana Victoni Tatiana Victoni Emmanuel Naline Emmanuel Naline Philippe Devillier Philippe Devillier Philippe Devillier |
| author_facet | Hélène Salvator Hélène Salvator Hélène Salvator Stanislas Grassin-Delyle Stanislas Grassin-Delyle Stanislas Grassin-Delyle Marion Brollo Louis-Jean Couderc Louis-Jean Couderc Louis-Jean Couderc Charlotte Abrial Tatiana Victoni Tatiana Victoni Emmanuel Naline Emmanuel Naline Philippe Devillier Philippe Devillier Philippe Devillier |
| author_sort | Hélène Salvator |
| collection | DOAJ |
| description | Background: Obesity is associated with an elevated risk of severe respiratory infections and inflammatory lung diseases. The objectives were to investigate 1) the production of adiponectin by human lung explants, 2) the expression of the adiponectin receptors AdipoR1 and AdipoR2 by human lung macrophages (LMs), and 3) the impact of recombinant human adiponectin and a small-molecule APN receptor agonist (AdipoRon) on LMs activation.Material and methods: Human parenchyma explants and LMs were isolated from patients operated for carcinoma. The LMs were cultured with recombinant adiponectin or AdipoRon and stimulated with lipopolysaccharide (10 ng ml−1), poly (I:C) (10 µg ml−1) or interleukin (IL)-4 (10 ng ml−1) for 24 h. Cytokines or adiponectin, released by explants or LMs, were measured using ELISAs. The mRNA levels of AdipoR1 and AdipoR2 were determined using real-time quantitative PCR. AdipoRs expression was also assessed with confocal microscopy.Results: Adiponectin was released by lung explants at a level negatively correlated with the donor’s body mass index. AdipoR1 and AdipoR2 were both expressed in LMs. Adiponectin (3–30 µg ml−1) and AdipoRon (25–50 μM) markedly inhibited the LPS- and poly (I:C)-induced release of Tumor Necrosis Factor-α, IL-6 and chemokines (CCL3, CCL4, CCL5, CXCL1, CXCL8, CXCL10) and the IL-4-induced release of chemokines (CCL13, CCL17, CCL22) in a concentration-dependent manner. Recombinant adiponectin produced in mammalian cells (lacking low molecular weight isoforms) had no effects on LMs.Conclusion and implications: The low-molecular-weight isoforms of adiponectin and AdipoRon have an anti-inflammatory activity in the lung environment. Targeting adiponectin receptors may constitute a new means of controlling airways inflammation. |
| first_indexed | 2024-12-22T13:49:28Z |
| format | Article |
| id | doaj.art-487e41bfe6df482785cff29b059f8963 |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-12-22T13:49:28Z |
| publishDate | 2021-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-487e41bfe6df482785cff29b059f89632022-12-21T18:23:42ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122021-08-011210.3389/fphar.2021.718929718929Adiponectin Inhibits the Production of TNF-α, IL-6 and Chemokines by Human Lung MacrophagesHélène Salvator0Hélène Salvator1Hélène Salvator2Stanislas Grassin-Delyle3Stanislas Grassin-Delyle4Stanislas Grassin-Delyle5Marion Brollo6Louis-Jean Couderc7Louis-Jean Couderc8Louis-Jean Couderc9Charlotte Abrial10Tatiana Victoni11Tatiana Victoni12Emmanuel Naline13Emmanuel Naline14Philippe Devillier15Philippe Devillier16Philippe Devillier17Laboratory of Research in respiratory Pharmacology- Virologie et Immunologie Moleculaire (VIM)- UMR 0892 Université Paris-Saclay, Suresnes, FranceFaculté des Sciences de la Santé Simone Veil, UVSQ Paris‐Saclay University, Montigny‐le‐Bretonneux, , FranceDepartment of Respiratory Diseases, Foch Hospital, Suresnes, FranceLaboratory of Research in respiratory Pharmacology- Virologie et Immunologie Moleculaire (VIM)- UMR 0892 Université Paris-Saclay, Suresnes, FranceFaculté des Sciences de la Santé Simone Veil, UVSQ Paris‐Saclay University, Montigny‐le‐Bretonneux, , FranceMass Spectrometry Platform and INSERM UMR1173, Montigny-le-Bretonneux, FranceLaboratory of Research in respiratory Pharmacology- Virologie et Immunologie Moleculaire (VIM)- UMR 0892 Université Paris-Saclay, Suresnes, FranceLaboratory of Research in respiratory Pharmacology- Virologie et Immunologie Moleculaire (VIM)- UMR 0892 Université Paris-Saclay, Suresnes, FranceFaculté des Sciences de la Santé Simone Veil, UVSQ Paris‐Saclay University, Montigny‐le‐Bretonneux, , FranceDepartment of Respiratory Diseases, Foch Hospital, Suresnes, FranceLaboratory of Research in respiratory Pharmacology- Virologie et Immunologie Moleculaire (VIM)- UMR 0892 Université Paris-Saclay, Suresnes, FranceLaboratory of Research in respiratory Pharmacology- Virologie et Immunologie Moleculaire (VIM)- UMR 0892 Université Paris-Saclay, Suresnes, FranceUniversity of Lyon, VetAgro Sup, APCSe, Marcy l’Étoile, FranceLaboratory of Research in respiratory Pharmacology- Virologie et Immunologie Moleculaire (VIM)- UMR 0892 Université Paris-Saclay, Suresnes, FranceFaculté des Sciences de la Santé Simone Veil, UVSQ Paris‐Saclay University, Montigny‐le‐Bretonneux, , FranceLaboratory of Research in respiratory Pharmacology- Virologie et Immunologie Moleculaire (VIM)- UMR 0892 Université Paris-Saclay, Suresnes, FranceFaculté des Sciences de la Santé Simone Veil, UVSQ Paris‐Saclay University, Montigny‐le‐Bretonneux, , FranceDepartment of Respiratory Diseases, Foch Hospital, Suresnes, FranceBackground: Obesity is associated with an elevated risk of severe respiratory infections and inflammatory lung diseases. The objectives were to investigate 1) the production of adiponectin by human lung explants, 2) the expression of the adiponectin receptors AdipoR1 and AdipoR2 by human lung macrophages (LMs), and 3) the impact of recombinant human adiponectin and a small-molecule APN receptor agonist (AdipoRon) on LMs activation.Material and methods: Human parenchyma explants and LMs were isolated from patients operated for carcinoma. The LMs were cultured with recombinant adiponectin or AdipoRon and stimulated with lipopolysaccharide (10 ng ml−1), poly (I:C) (10 µg ml−1) or interleukin (IL)-4 (10 ng ml−1) for 24 h. Cytokines or adiponectin, released by explants or LMs, were measured using ELISAs. The mRNA levels of AdipoR1 and AdipoR2 were determined using real-time quantitative PCR. AdipoRs expression was also assessed with confocal microscopy.Results: Adiponectin was released by lung explants at a level negatively correlated with the donor’s body mass index. AdipoR1 and AdipoR2 were both expressed in LMs. Adiponectin (3–30 µg ml−1) and AdipoRon (25–50 μM) markedly inhibited the LPS- and poly (I:C)-induced release of Tumor Necrosis Factor-α, IL-6 and chemokines (CCL3, CCL4, CCL5, CXCL1, CXCL8, CXCL10) and the IL-4-induced release of chemokines (CCL13, CCL17, CCL22) in a concentration-dependent manner. Recombinant adiponectin produced in mammalian cells (lacking low molecular weight isoforms) had no effects on LMs.Conclusion and implications: The low-molecular-weight isoforms of adiponectin and AdipoRon have an anti-inflammatory activity in the lung environment. Targeting adiponectin receptors may constitute a new means of controlling airways inflammation.https://www.frontiersin.org/articles/10.3389/fphar.2021.718929/fulladiponectinobesityhuman lung macrophagecytokineadiporonLPS |
| spellingShingle | Hélène Salvator Hélène Salvator Hélène Salvator Stanislas Grassin-Delyle Stanislas Grassin-Delyle Stanislas Grassin-Delyle Marion Brollo Louis-Jean Couderc Louis-Jean Couderc Louis-Jean Couderc Charlotte Abrial Tatiana Victoni Tatiana Victoni Emmanuel Naline Emmanuel Naline Philippe Devillier Philippe Devillier Philippe Devillier Adiponectin Inhibits the Production of TNF-α, IL-6 and Chemokines by Human Lung Macrophages Frontiers in Pharmacology adiponectin obesity human lung macrophage cytokine adiporon LPS |
| title | Adiponectin Inhibits the Production of TNF-α, IL-6 and Chemokines by Human Lung Macrophages |
| title_full | Adiponectin Inhibits the Production of TNF-α, IL-6 and Chemokines by Human Lung Macrophages |
| title_fullStr | Adiponectin Inhibits the Production of TNF-α, IL-6 and Chemokines by Human Lung Macrophages |
| title_full_unstemmed | Adiponectin Inhibits the Production of TNF-α, IL-6 and Chemokines by Human Lung Macrophages |
| title_short | Adiponectin Inhibits the Production of TNF-α, IL-6 and Chemokines by Human Lung Macrophages |
| title_sort | adiponectin inhibits the production of tnf α il 6 and chemokines by human lung macrophages |
| topic | adiponectin obesity human lung macrophage cytokine adiporon LPS |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2021.718929/full |
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