FFC#19/2016

Resolvin D1 for targeting chronic lung inflammation, infection, and damage in cystic fibrosis

FFC#19/2016

Resolvin D1 for targeting chronic lung inflammation, infection, and damage in cystic fibrosis

PRINCIPAL INVESTIGATOR

Antonio Recchiuti (Dipartimento di Scienze Mediche, Orali e Biotecnologie – Centro di Eccellenza delle Scienze dell’Invecchiamento, Università G. D’Annunzio, Chieti-Pescara)

RESEARCHERS

11

CATEGORY

AREA 4 Lung inflammation

DURATION

2 years

GOAL

€ 100.000 €

RESULTS

RvD1 significantly dampened bacterial burden in Cftr-/- mice chronically infected with a clinical strain of Pa. RvD1 also markedly dampened total leukocytes and PMN (polymorphonucleates) infiltration and ameliorated histological scores of lung pathology. In addition, RvD1 increased the percentage of phagocytosis of Pa by CF mouse and human CF macrophages along with a significant reduction in interleukin-8, -6, and -17. In primary CF airway epithelial cells (CFAEC) and macrophages (MΦ.) RvD1 regulated genes involved in inflammation and anti-microbial responses. These results indicate that RvD1 enhances the resolution of PA infection and inflammation in CF cellular and animal models, thus fostering further studies in preclinical models and clinical trials, as well as a spin-off for research applications in a relatively short time for exploring RvD1 as a novel therapeutic for CF.


 Pubblications

– Pierdomenico AM, Patruno S, Codagnone M et al. “microRNA-181b is increased in cystic fibrosis cells and impairs lipoxin A4 receptor-dependent mechanisms of inflammation resolution and antimicrobial defense” SCI REP 2017 Oct 18;7(1):13519 11-mag-18
– Isopi E, Mattoscio D, Codagnone M et al “Resolution of chronic lung inflammation and infection in cystic fibrosis with resolvin D1” submitted

Congress abstract

– Isopi E, Mattoscio D, Mari VC et al. “Harnessing resolution mediators as novel therapeutic for cystic fibrosis” North American Cystic Fibrosis Conference (NACF), October 18-20, 2018, Denver, CO, USA (Thematic poster view)
– Mattoscio D, Isopi E, Mari VC et al. “Resolvin D1 for targeting lung inflammation, infection, and damage in CF” North American Cystic Fibrosis Conference (NACF), October 18-20, 2018, Denver, CO, USA (Workshop presentation)
– Recchiuti A “Resolvins, lipoxins, and maresins in resolution of inflammation in cystic fibrosis “North American Cystic Fibrosis Conference (NACF), October 18-20, 2018, Denver, CO, USA (Invited Symposium lecture)
– Recchiuti A, Isopi E, Mattoscio D et al. “Harnessing resolution mediators as innovative therapeutics for cystic fibrosis” 2nd International Conference on Pharmacology, August 16-18, Rome, Italy

OTHER RESULTS

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Two molecules are effective in activating Heat Shock Proteins and enhancing the action of CFTR correctors with the F508del mutation in vitro.

FFC#5/2024

Some peptide nucleic acids (PNAs) re-sensitise Pseudomonas aeruginosa to the antibiotic meropenem in vitro and reduce its virulence.

FFC#1/2023

Tezacaftor, one of the components of Kaftrio, induces an accumulation of dihydroceramides both in vitro and in vivo in animal models