Resolvin D1 Reduces Lung Infection and Inflammation Activating Resolution in Cystic Fibrosis
Non-resolving lung inflammation and Pseudomonas aeruginosa infections are the underlying cause of morbidity and mortality in cystic fibrosis (CF). The endogenous lipid mediator resolvin (Rv) D1 is a potent regulator of resolution, and its roles, actions, and therapeutic potential in CF are of intere...
| Main Authors: | , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2020-04-01
|
| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2020.00581/full |
| _version_ | 1818201644043599872 |
|---|---|
| author | Elisa Isopi Domenico Mattoscio Marilina Codagnone Veronica Cecilia Mari Alessia Lamolinara Sara Patruno Marco D’Aurora Eleonora Cianci Annalisa Nespoli Sara Franchi Valentina Gatta Marc Dubourdeau Paolo Moretti Maria Di Sabatino Manuela Iezzi Mario Romano Antonio Recchiuti |
| author_facet | Elisa Isopi Domenico Mattoscio Marilina Codagnone Veronica Cecilia Mari Alessia Lamolinara Sara Patruno Marco D’Aurora Eleonora Cianci Annalisa Nespoli Sara Franchi Valentina Gatta Marc Dubourdeau Paolo Moretti Maria Di Sabatino Manuela Iezzi Mario Romano Antonio Recchiuti |
| author_sort | Elisa Isopi |
| collection | DOAJ |
| description | Non-resolving lung inflammation and Pseudomonas aeruginosa infections are the underlying cause of morbidity and mortality in cystic fibrosis (CF). The endogenous lipid mediator resolvin (Rv) D1 is a potent regulator of resolution, and its roles, actions, and therapeutic potential in CF are of interest. Here, we investigated actions and efficacy of RvD1 in preclinical models of cystic fibrosis. Cftr knockout mice with chronic P. aeruginosa lung infection were treated with RvD1 to assess differences in lung bacterial load, inflammation, and tissue damage. Cells from volunteers with CF were treated with RvD1 during ex vivo infection with P. aeruginosa, and effects on phagocytosis and inflammatory signaling were determined. In CF mice, RvD1 reduced bacterial burden, neutrophil infiltration, and histological signs of lung pathology, improving clinical scores of diseases. Mechanistically, RvD1 increased macrophage-mediated bacterial and leukocyte clearance in vivo. The clinical significance of these findings is supported by actions in primary leukocytes and epithelial cells from volunteers with CF where RvD1 enhanced P. aeruginosa phagocytosis and reduced genes and proteins associated to NF-κB activation and leukocyte infiltration. Concentration of RvD1 in sputum from patients with CF was also inversely correlated to those of cytokines and chemokines involved in CF lung pathology. These findings demonstrate efficacy of RvD1 in enhancing resolution of lung inflammation and infections and provide proof of concept for its potential as a prototypic novel pro-resolutive therapeutic approach for CF. |
| first_indexed | 2024-12-12T02:56:49Z |
| format | Article |
| id | doaj.art-936a8995b9d341228266da159d14c588 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-12T02:56:49Z |
| publishDate | 2020-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-936a8995b9d341228266da159d14c5882022-12-22T00:40:44ZengFrontiers Media S.A.Frontiers in Immunology1664-32242020-04-011110.3389/fimmu.2020.00581519983Resolvin D1 Reduces Lung Infection and Inflammation Activating Resolution in Cystic FibrosisElisa Isopi0Domenico Mattoscio1Marilina Codagnone2Veronica Cecilia Mari3Alessia Lamolinara4Sara Patruno5Marco D’Aurora6Eleonora Cianci7Annalisa Nespoli8Sara Franchi9Valentina Gatta10Marc Dubourdeau11Paolo Moretti12Maria Di Sabatino13Manuela Iezzi14Mario Romano15Antonio Recchiuti16Center for Advanced Studies and Technology, Department of Medical, Oral and Biotechnology Science, “G. d’Annunzio” University of Chieti – Pescara, Chieti, ItalyCenter for Advanced Studies and Technology, Department of Medical, Oral and Biotechnology Science, “G. d’Annunzio” University of Chieti – Pescara, Chieti, ItalyCenter for Advanced Studies and Technology, Department of Medical, Oral and Biotechnology Science, “G. d’Annunzio” University of Chieti – Pescara, Chieti, ItalyCenter for Advanced Studies and Technology, Department of Medical, Oral and Biotechnology Science, “G. d’Annunzio” University of Chieti – Pescara, Chieti, ItalyCenter for Advanced Studies and Technology, Department of Medicine and Aging Sciences, “G. d’Annunzio” University of Chieti – Pescara, Chieti, ItalyCenter for Advanced Studies and Technology, Department of Medical, Oral and Biotechnology Science, “G. d’Annunzio” University of Chieti – Pescara, Chieti, ItalyCenter for Advanced Studies and Technology, Department of Psychological, Humanistic and Territorial Sciences, “G. d’Annunzio” University of Chieti – Pescara, Chieti, ItalyCenter for Advanced Studies and Technology, Department of Medical, Oral and Biotechnology Science, “G. d’Annunzio” University of Chieti – Pescara, Chieti, ItalyCenter for Advanced Studies and Technology, Department of Medicine and Aging Sciences, “G. d’Annunzio” University of Chieti – Pescara, Chieti, ItalyCenter for Advanced Studies and Technology, Department of Psychological, Humanistic and Territorial Sciences, “G. d’Annunzio” University of Chieti – Pescara, Chieti, ItalyCenter for Advanced Studies and Technology, Department of Psychological, Humanistic and Territorial Sciences, “G. d’Annunzio” University of Chieti – Pescara, Chieti, ItalyAmbiotis SAS, Toulouse, FranceCystic Fibrosis Regional Center, Ospedale “San Liberatore,”Atri, ItalyCystic Fibrosis Regional Center, Ospedale “San Liberatore,”Atri, ItalyCenter for Advanced Studies and Technology, Department of Medicine and Aging Sciences, “G. d’Annunzio” University of Chieti – Pescara, Chieti, ItalyCenter for Advanced Studies and Technology, Department of Medical, Oral and Biotechnology Science, “G. d’Annunzio” University of Chieti – Pescara, Chieti, ItalyCenter for Advanced Studies and Technology, Department of Medical, Oral and Biotechnology Science, “G. d’Annunzio” University of Chieti – Pescara, Chieti, ItalyNon-resolving lung inflammation and Pseudomonas aeruginosa infections are the underlying cause of morbidity and mortality in cystic fibrosis (CF). The endogenous lipid mediator resolvin (Rv) D1 is a potent regulator of resolution, and its roles, actions, and therapeutic potential in CF are of interest. Here, we investigated actions and efficacy of RvD1 in preclinical models of cystic fibrosis. Cftr knockout mice with chronic P. aeruginosa lung infection were treated with RvD1 to assess differences in lung bacterial load, inflammation, and tissue damage. Cells from volunteers with CF were treated with RvD1 during ex vivo infection with P. aeruginosa, and effects on phagocytosis and inflammatory signaling were determined. In CF mice, RvD1 reduced bacterial burden, neutrophil infiltration, and histological signs of lung pathology, improving clinical scores of diseases. Mechanistically, RvD1 increased macrophage-mediated bacterial and leukocyte clearance in vivo. The clinical significance of these findings is supported by actions in primary leukocytes and epithelial cells from volunteers with CF where RvD1 enhanced P. aeruginosa phagocytosis and reduced genes and proteins associated to NF-κB activation and leukocyte infiltration. Concentration of RvD1 in sputum from patients with CF was also inversely correlated to those of cytokines and chemokines involved in CF lung pathology. These findings demonstrate efficacy of RvD1 in enhancing resolution of lung inflammation and infections and provide proof of concept for its potential as a prototypic novel pro-resolutive therapeutic approach for CF.https://www.frontiersin.org/article/10.3389/fimmu.2020.00581/fullpro-resolving lipid mediators (SPM)inflammationresolutionmacrophagesneutrophilsinfection |
| spellingShingle | Elisa Isopi Domenico Mattoscio Marilina Codagnone Veronica Cecilia Mari Alessia Lamolinara Sara Patruno Marco D’Aurora Eleonora Cianci Annalisa Nespoli Sara Franchi Valentina Gatta Marc Dubourdeau Paolo Moretti Maria Di Sabatino Manuela Iezzi Mario Romano Antonio Recchiuti Resolvin D1 Reduces Lung Infection and Inflammation Activating Resolution in Cystic Fibrosis Frontiers in Immunology pro-resolving lipid mediators (SPM) inflammation resolution macrophages neutrophils infection |
| title | Resolvin D1 Reduces Lung Infection and Inflammation Activating Resolution in Cystic Fibrosis |
| title_full | Resolvin D1 Reduces Lung Infection and Inflammation Activating Resolution in Cystic Fibrosis |
| title_fullStr | Resolvin D1 Reduces Lung Infection and Inflammation Activating Resolution in Cystic Fibrosis |
| title_full_unstemmed | Resolvin D1 Reduces Lung Infection and Inflammation Activating Resolution in Cystic Fibrosis |
| title_short | Resolvin D1 Reduces Lung Infection and Inflammation Activating Resolution in Cystic Fibrosis |
| title_sort | resolvin d1 reduces lung infection and inflammation activating resolution in cystic fibrosis |
| topic | pro-resolving lipid mediators (SPM) inflammation resolution macrophages neutrophils infection |
| url | https://www.frontiersin.org/article/10.3389/fimmu.2020.00581/full |
| work_keys_str_mv | AT elisaisopi resolvind1reduceslunginfectionandinflammationactivatingresolutionincysticfibrosis AT domenicomattoscio resolvind1reduceslunginfectionandinflammationactivatingresolutionincysticfibrosis AT marilinacodagnone resolvind1reduceslunginfectionandinflammationactivatingresolutionincysticfibrosis AT veronicaceciliamari resolvind1reduceslunginfectionandinflammationactivatingresolutionincysticfibrosis AT alessialamolinara resolvind1reduceslunginfectionandinflammationactivatingresolutionincysticfibrosis AT sarapatruno resolvind1reduceslunginfectionandinflammationactivatingresolutionincysticfibrosis AT marcodaurora resolvind1reduceslunginfectionandinflammationactivatingresolutionincysticfibrosis AT eleonoracianci resolvind1reduceslunginfectionandinflammationactivatingresolutionincysticfibrosis AT annalisanespoli resolvind1reduceslunginfectionandinflammationactivatingresolutionincysticfibrosis AT sarafranchi resolvind1reduceslunginfectionandinflammationactivatingresolutionincysticfibrosis AT valentinagatta resolvind1reduceslunginfectionandinflammationactivatingresolutionincysticfibrosis AT marcdubourdeau resolvind1reduceslunginfectionandinflammationactivatingresolutionincysticfibrosis AT paolomoretti resolvind1reduceslunginfectionandinflammationactivatingresolutionincysticfibrosis AT mariadisabatino resolvind1reduceslunginfectionandinflammationactivatingresolutionincysticfibrosis AT manuelaiezzi resolvind1reduceslunginfectionandinflammationactivatingresolutionincysticfibrosis AT marioromano resolvind1reduceslunginfectionandinflammationactivatingresolutionincysticfibrosis AT antoniorecchiuti resolvind1reduceslunginfectionandinflammationactivatingresolutionincysticfibrosis |