Receptor for Advanced Glycation End-Products Promotes Activation of Alveolar Macrophages through the NLRP3 Inflammasome/TXNIP Axis in Acute Lung Injury
The roles of thioredoxin-interacting protein (TXNIP) and receptor for advanced glycation end-products (RAGE)-dependent mechanisms of NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome-driven macrophage activation during acute lung injury are underinvestigated. Cultured THP-1 ma...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-10-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/19/11659 |
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| author | Woodys Lenga Ma Bonda Marianne Fournet Ruoyang Zhai Jean Lutz Raiko Blondonnet Céline Bourgne Charlotte Leclaire Cécile Saint-Béat Camille Theilliere Corinne Belville Damien Bouvier Loïc Blanchon Marc Berger Vincent Sapin Matthieu Jabaudon |
| author_facet | Woodys Lenga Ma Bonda Marianne Fournet Ruoyang Zhai Jean Lutz Raiko Blondonnet Céline Bourgne Charlotte Leclaire Cécile Saint-Béat Camille Theilliere Corinne Belville Damien Bouvier Loïc Blanchon Marc Berger Vincent Sapin Matthieu Jabaudon |
| author_sort | Woodys Lenga Ma Bonda |
| collection | DOAJ |
| description | The roles of thioredoxin-interacting protein (TXNIP) and receptor for advanced glycation end-products (RAGE)-dependent mechanisms of NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome-driven macrophage activation during acute lung injury are underinvestigated. Cultured THP-1 macrophages were treated with a RAGE agonist (S100A12), with or without a RAGE antagonist; cytokine release and intracytoplasmic production of reactive oxygen species (ROS) were assessed in response to small interfering RNA knockdowns of TXNIP and NLRP3. Lung expressions of TXNIP and NLRP3 and alveolar levels of IL-1β and S100A12 were measured in mice after acid-induced lung injury, with or without administration of RAGE inhibitors. Alveolar macrophages from patients with acute respiratory distress syndrome and from mechanically ventilated controls were analyzed using fluorescence-activated cell sorting. In vitro, RAGE promoted cytokine release and ROS production in macrophages and upregulated NLRP3 and TXNIP mRNA expression in response to S100A12. TXNIP inhibition downregulated NLRP3 gene expression and RAGE-mediated release of IL-1β by macrophages in vitro. In vivo, RAGE, NLRP3 and TXNIP lung expressions were upregulated during experimental acute lung injury, a phenomenon being reversed by RAGE inhibition. The numbers of cells expressing RAGE, NLRP3 and TXNIP among a specific subpopulation of CD16+CD14+CD206- (“pro-inflammatory”) alveolar macrophages were higher in patients with lung injury. This study provides a novel proof-of-concept of complex RAGE–TXNIP–NLRP3 interactions during macrophage activation in acute lung injury. |
| first_indexed | 2024-03-09T21:38:06Z |
| format | Article |
| id | doaj.art-44f15d27032c4f9cb3bf44b17cabac21 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T21:38:06Z |
| publishDate | 2022-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-44f15d27032c4f9cb3bf44b17cabac212023-11-23T20:37:04ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-10-0123191165910.3390/ijms231911659Receptor for Advanced Glycation End-Products Promotes Activation of Alveolar Macrophages through the NLRP3 Inflammasome/TXNIP Axis in Acute Lung InjuryWoodys Lenga Ma Bonda0Marianne Fournet1Ruoyang Zhai2Jean Lutz3Raiko Blondonnet4Céline Bourgne5Charlotte Leclaire6Cécile Saint-Béat7Camille Theilliere8Corinne Belville9Damien Bouvier10Loïc Blanchon11Marc Berger12Vincent Sapin13Matthieu Jabaudon14iGReD, Université Clermont Auvergne, CNRS, INSERM, 63000 Clermont-Ferrand, FranceiGReD, Université Clermont Auvergne, CNRS, INSERM, 63000 Clermont-Ferrand, FranceiGReD, Université Clermont Auvergne, CNRS, INSERM, 63000 Clermont-Ferrand, FranceDepartment of Perioperative Medicine, CHU Clermont-Ferrand, 63000 Clermont-Ferrand, FranceiGReD, Université Clermont Auvergne, CNRS, INSERM, 63000 Clermont-Ferrand, FranceDepartment of Hematology and Immunology, CHU Clermont-Ferrand, 63000 Clermont-Ferrand, FranceiGReD, Université Clermont Auvergne, CNRS, INSERM, 63000 Clermont-Ferrand, FranceiGReD, Université Clermont Auvergne, CNRS, INSERM, 63000 Clermont-Ferrand, FranceiGReD, Université Clermont Auvergne, CNRS, INSERM, 63000 Clermont-Ferrand, FranceiGReD, Université Clermont Auvergne, CNRS, INSERM, 63000 Clermont-Ferrand, FranceiGReD, Université Clermont Auvergne, CNRS, INSERM, 63000 Clermont-Ferrand, FranceiGReD, Université Clermont Auvergne, CNRS, INSERM, 63000 Clermont-Ferrand, FranceDepartment of Hematology and Immunology, CHU Clermont-Ferrand, 63000 Clermont-Ferrand, FranceiGReD, Université Clermont Auvergne, CNRS, INSERM, 63000 Clermont-Ferrand, FranceiGReD, Université Clermont Auvergne, CNRS, INSERM, 63000 Clermont-Ferrand, FranceThe roles of thioredoxin-interacting protein (TXNIP) and receptor for advanced glycation end-products (RAGE)-dependent mechanisms of NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome-driven macrophage activation during acute lung injury are underinvestigated. Cultured THP-1 macrophages were treated with a RAGE agonist (S100A12), with or without a RAGE antagonist; cytokine release and intracytoplasmic production of reactive oxygen species (ROS) were assessed in response to small interfering RNA knockdowns of TXNIP and NLRP3. Lung expressions of TXNIP and NLRP3 and alveolar levels of IL-1β and S100A12 were measured in mice after acid-induced lung injury, with or without administration of RAGE inhibitors. Alveolar macrophages from patients with acute respiratory distress syndrome and from mechanically ventilated controls were analyzed using fluorescence-activated cell sorting. In vitro, RAGE promoted cytokine release and ROS production in macrophages and upregulated NLRP3 and TXNIP mRNA expression in response to S100A12. TXNIP inhibition downregulated NLRP3 gene expression and RAGE-mediated release of IL-1β by macrophages in vitro. In vivo, RAGE, NLRP3 and TXNIP lung expressions were upregulated during experimental acute lung injury, a phenomenon being reversed by RAGE inhibition. The numbers of cells expressing RAGE, NLRP3 and TXNIP among a specific subpopulation of CD16+CD14+CD206- (“pro-inflammatory”) alveolar macrophages were higher in patients with lung injury. This study provides a novel proof-of-concept of complex RAGE–TXNIP–NLRP3 interactions during macrophage activation in acute lung injury.https://www.mdpi.com/1422-0067/23/19/11659acute respiratory distress syndromeacute lung injurymacrophage activationalveolar inflammationreceptor for advanced glycation end-productsthioredoxin-interacting protein |
| spellingShingle | Woodys Lenga Ma Bonda Marianne Fournet Ruoyang Zhai Jean Lutz Raiko Blondonnet Céline Bourgne Charlotte Leclaire Cécile Saint-Béat Camille Theilliere Corinne Belville Damien Bouvier Loïc Blanchon Marc Berger Vincent Sapin Matthieu Jabaudon Receptor for Advanced Glycation End-Products Promotes Activation of Alveolar Macrophages through the NLRP3 Inflammasome/TXNIP Axis in Acute Lung Injury International Journal of Molecular Sciences acute respiratory distress syndrome acute lung injury macrophage activation alveolar inflammation receptor for advanced glycation end-products thioredoxin-interacting protein |
| title | Receptor for Advanced Glycation End-Products Promotes Activation of Alveolar Macrophages through the NLRP3 Inflammasome/TXNIP Axis in Acute Lung Injury |
| title_full | Receptor for Advanced Glycation End-Products Promotes Activation of Alveolar Macrophages through the NLRP3 Inflammasome/TXNIP Axis in Acute Lung Injury |
| title_fullStr | Receptor for Advanced Glycation End-Products Promotes Activation of Alveolar Macrophages through the NLRP3 Inflammasome/TXNIP Axis in Acute Lung Injury |
| title_full_unstemmed | Receptor for Advanced Glycation End-Products Promotes Activation of Alveolar Macrophages through the NLRP3 Inflammasome/TXNIP Axis in Acute Lung Injury |
| title_short | Receptor for Advanced Glycation End-Products Promotes Activation of Alveolar Macrophages through the NLRP3 Inflammasome/TXNIP Axis in Acute Lung Injury |
| title_sort | receptor for advanced glycation end products promotes activation of alveolar macrophages through the nlrp3 inflammasome txnip axis in acute lung injury |
| topic | acute respiratory distress syndrome acute lung injury macrophage activation alveolar inflammation receptor for advanced glycation end-products thioredoxin-interacting protein |
| url | https://www.mdpi.com/1422-0067/23/19/11659 |
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