FFC#22/2014

Targeting pathogenic pathways leading to inflammatory Th17 responses in cystic fibrosis: from drug discovery to preclinical validation

FFC#22/2014

Targeting pathogenic pathways leading to inflammatory Th17 responses in cystic fibrosis: from drug discovery to preclinical validation

PRINCIPAL INVESTIGATOR

Luigina Romani (Dip. di Medicina Sperimentale, Università di Perugia)

RESEARCHERS

12

CATEGORY

AREA 4 Lung inflammation

DURATION

2 years

GOAL

€ 70.000

RESULTS

Different components of inflammasome were studied and it was shown that NLRP3 more than NLRC4 contributed to pathogenic inflammatory responses in murine and human CF epithelial cells; moreover, it correlated with lower levels of IL-1Ra production and reduced NLRC4 activation. Pathogenic NLRP3 activity could be negatively regulated by IL-1Ra and this provide a proof-of- concept evidence that IL-1Ra may limit the pathological consequences of microbial colonization in CF. Genetic analysis supported the role of NLRC4 and IL-1Ra in determining the state of microbial colonization in CF patients. These promising results highlight the possibility of repurposing Anakinra as a therapeutic strategy in FC.

OTHER RESULTS

FFC #3/2024

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