Spermidine and spermine exert protective effects within the lung.
Marcin WawrzyniakDavid GroegerRemo FreiRuth FerstlPaulina WawrzyniakKrzysztof KrawczykBenoit PuginWeronika BarcikPatrick WestermannAnita DreherMichael ScharlMarek JutelCezmi A AkdisLiam O MahonyPublished in: Pharmacology research & perspectives (2022)
Asthma is a heterologous disease that is influenced by complex interactions between multiple environmental exposures, metabolism, and host immunoregulatory processes. Specific metabolites are increasingly recognized to influence respiratory inflammation. However, the role of protein-derived metabolites in regulating inflammatory responses in the lung are poorly described. The aims of the present study were to quantify polyamine levels in bronchoalveolar lavages (BALs) from healthy volunteers and asthma patients, and to evaluate the impact of each polyamine on inflammatory responses using in vitro models and in a house dust mite (HDM)-induced respiratory allergy model. Spermidine levels were decreased, while cadaverine levels were increased in BALs from asthma patients compared to healthy controls, using Ultra Performance Liquid Chromatography (UPLC). Both spermine and spermidine inhibit lipopolysaccharide (LPS)-induced cytokine secretion from human peripheral blood mononuclear cells (PBMCs) and dendritic cells (DCs) in vitro. In addition, oral gavage with spermine or spermidine modulate HDM-induced cell infiltration, cytokine secretion, and epithelial cell tight junction expression in murine models. Spermidine also reduces airway hyper-responsiveness. These results suggest that modulation of polyamine metabolism, in particular spermidine, is associated with respiratory inflammation and these molecules and pathways should be further explored as biomarkers of disease and potential targets for novel therapies.
Keyphrases
- lps induced
- end stage renal disease
- dendritic cells
- chronic obstructive pulmonary disease
- ejection fraction
- newly diagnosed
- inflammatory response
- chronic kidney disease
- endothelial cells
- peritoneal dialysis
- high glucose
- liquid chromatography
- prognostic factors
- ms ms
- immune response
- lung function
- poor prognosis
- high resolution
- allergic rhinitis
- mass spectrometry
- human health
- risk assessment
- drug induced
- diabetic rats
- regulatory t cells
- polycyclic aromatic hydrocarbons
- atopic dermatitis
- single cell
- heavy metals
- stress induced