Resolvin D1 Reduces Lung Infection and Inflammation Activating Resolution in Cystic Fibrosis.

Frontiers in Immunology
Elisa IsopiAntonio Recchiuti

Abstract

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. C...Continue Reading

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Citations

Sep 5, 2020·Essays in Biochemistry·Nan Chiang, Charles N Serhan
Aug 28, 2020·Frontiers in Pharmacology·Antonio RecchiutiMario Romano
Sep 29, 2020·Frontiers in Pharmacology·Maelle BriottetValerie Urbach
Oct 8, 2020·Journal of Cellular and Molecular Medicine·Anna LiXietong Wang
Sep 16, 2020·International Journal of Molecular Sciences·Antonio RecchiutiDomenico Mattoscio
Oct 25, 2020·The Journal of Physiological Sciences : JPS·Ruiqi JiaJunwei Cui
Nov 30, 2020·BioFactors·Shayna Sandhaus, Andrew G Swick
Feb 13, 2021·Pathogens·David Jiao ZhengBryan Heit
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Dec 27, 2021·Current Opinion in Clinical Nutrition and Metabolic Care·R Elaine CagninaBruce D Levy

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Methods Mentioned

BETA
bronchoalveolar lavage
ELISA
FCS
flow cytometry
PCR
bronchoalveolar
nuclear translocation

Software Mentioned

DeNovo
Cluster
TreeView
Ambiotis SAS
IPA

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