Chronic inflammatory diseases affecting airway mucosa, such as Cystic Fibrosis (CF), are characterized by defective immunity and recurrent infectio communities. Aspergillus fumigatus is the most prevalent filamentous fungus in the respiratory tract of CF patients, contributing to lung deterioratio impairment and hyper-inflammation with sphingolipid ceramide accumulating in CF airways. Autophagy is a master regulator of the stress response tha degradation. Myriocin, an orphan drug with pleiotropic action, reduces pro-inflammatory lipids accumulation, promoting antioxidant response to stress a transcriptional activity in CF broncho-epithelial cells that significantly differs from the healthy broncho-epithelium response, involving a higher numbe in a positive modulation of the transcriptional machinery that leads to better clearance of A. fumigatus infection. Indeed, Myriocin-regulated genes belo response, lipid metabolism, and proteostasis. We further corroborate this observation by studying Myriocin-induced transcriptional activities in monoc with A. fumigatus. Myriocin not only modulates genes involved in controlling inflammation, infection and lipid metabolism, but also significantly enhan conidia. In conclusion, sphingolipid synthesis inhibition modulates cell metabolism and stress response restoring CF deficiency.

Sphingolipid Synthesis Inhibition Modulates Transcriptional Phenotype and Promotes the Defense against Aspergillus Fumigatus Infection in Cystic Fibrosis / E. Ottaviano, A. Mingione, T. Armeni, M. Cipolli, N. Cirilli, M. Barcella, I. Merelli, R. Ghidoni, P. Signorelli, E. Borghi. ((Intervento presentato al American Society for Microbiology. convegno ASM MICROBE tenutosi a Chicago nel 2020.

Sphingolipid Synthesis Inhibition Modulates Transcriptional Phenotype and Promotes the Defense against Aspergillus Fumigatus Infection in Cystic Fibrosis

E. Ottaviano;A. Mingione;M. Barcella;R. Ghidoni;P. Signorelli;E. Borghi
2020

Abstract

Chronic inflammatory diseases affecting airway mucosa, such as Cystic Fibrosis (CF), are characterized by defective immunity and recurrent infectio communities. Aspergillus fumigatus is the most prevalent filamentous fungus in the respiratory tract of CF patients, contributing to lung deterioratio impairment and hyper-inflammation with sphingolipid ceramide accumulating in CF airways. Autophagy is a master regulator of the stress response tha degradation. Myriocin, an orphan drug with pleiotropic action, reduces pro-inflammatory lipids accumulation, promoting antioxidant response to stress a transcriptional activity in CF broncho-epithelial cells that significantly differs from the healthy broncho-epithelium response, involving a higher numbe in a positive modulation of the transcriptional machinery that leads to better clearance of A. fumigatus infection. Indeed, Myriocin-regulated genes belo response, lipid metabolism, and proteostasis. We further corroborate this observation by studying Myriocin-induced transcriptional activities in monoc with A. fumigatus. Myriocin not only modulates genes involved in controlling inflammation, infection and lipid metabolism, but also significantly enhan conidia. In conclusion, sphingolipid synthesis inhibition modulates cell metabolism and stress response restoring CF deficiency.
Cystic fibrosis; Aspergillus; Sphingolipids
Settore MED/07 - Microbiologia e Microbiologia Clinica
Sphingolipid Synthesis Inhibition Modulates Transcriptional Phenotype and Promotes the Defense against Aspergillus Fumigatus Infection in Cystic Fibrosis / E. Ottaviano, A. Mingione, T. Armeni, M. Cipolli, N. Cirilli, M. Barcella, I. Merelli, R. Ghidoni, P. Signorelli, E. Borghi. ((Intervento presentato al American Society for Microbiology. convegno ASM MICROBE tenutosi a Chicago nel 2020.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/741555
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