The project focused on the mode of action of Myriocin as an anti-inflammatory and antimicrobial therapeutic agent. Myriocin treatment was evaluated in CFTR-F508del TR bronchoepithelial cell line and in peripheral blood monocytes derived from CF patients, either homozygous or heterozygous for ΔF508; it was seen to act as an effective inducer of autophagy, which is defective in CF. Moreover, it activates key transcriptional factors, TFEB, FOXO1a and PPARgamma, involved in autophagy induction, mitochondrial activity, energy production, lipid mobilization and consume. Myriocin significantly increases the transcription of downstream genes, regulating fatty acids entry in mitochondria (CTP1a and 1b; FATP) and their oxidation (ACAD L) and significantly reduces pathological accumulation of lipid un-organized deposits. Finally Myriocin treatment of peripheral blood monocytes from CF patients, infected with A. fumigatus, significantly increases their pathogen killing ability. The perspective is Myriocin may have a therapeutic action against infection and presents interesting effects on lipid metabolism.

Pubblications

– Caretti A, Vasso M, Bonezzi FT et al. “Myriocin treatment of CF lung infection and inflammation: complex analyses for enigmatic lipids” Naunyn Schmiedebergs Arch Pharmacol 2017 Aug;390(8):775-790.