Table 1.

Effects of sphingolipids in pulmonary diseases

Stimulus	Sphingolipid	Enzyme/pathway	Cell fate	Pathophysiological effect	Disease state	Reference
Sepsis, inhalation of harmful substances	↑ S1P	NSM pathway, ceramide is converted to S1P	↓ Neutrophil apoptosis	Expedites inflammation, increase in proteases and ROS resulting in damage to lung tissues	Acute lung injury/ARDS	[142]
Mechanical ventilation, high oxygen	↑ Ceramide	? (Possibly de novo synthesis pathway)	↑ Alveolar epithelial cell apoptosis	Halt in alveolarization, fewer and larger alveoli	BPD	[21, 118]
Airway response to allergen	↑ S1P	Mitogenic factor, facilitates G1/S progression	↑ Airway smooth muscle cell proliferation	Airway wall remodeling	Asthma	[161]
Genetic variation at the 17q21 locus (ORMDL3 protein)	↓ Ceramide	Inhibition of SPT	Increase of S1P, decrease of ceramide results in cell survival and proliferation	Genetic predisposition to play role in pathogenesis of asthma	Asthma	[159, 166, 167]
Inhalation of cigarette smoke/pollutants	↑ Ceramide	↑ De novo synthesis	↑ Alveolar epithelial cell apoptosis	Loss of alveolar surface area available for gas exchange	COPD/emphysema	[19]
Inhalation of cigarette smoke/pollutants	↑ Ceramide	?	↑ Impaired autophagy	Accumulation of impaired autophagy marker p62 in autophagosomes	COPD/emphysema	[184, 190]
P. aeruginosa infection in CFTR-deficient mice	↑ Ceramide	? (Possibly by a shift in balance of enzymes involved in ceramide metabolism)	↑ Bronchial cell apoptosis	Bronchial cell apoptosis and DNA deposition in the upper airways	Cystic fibrosis	[6]

? means currently unknown