Unleashing AdipoRon's Potential: A Fresh Approach to Tackle Infections in Bronchiectasis via Sphingosine Metabolism Modulation.

PURPOSE

Bronchiectasis patients are prone to infection due to decreased level of sphingosine in airway. Adiponectin receptor agonist AdipoRon activates the intrinsic ceramidase activity of adiponectin receptor 1 (AdipoR1) and positively regulates sphingosine metabolism. This study aimed to investigate the potential therapeutic benefit of AdipoRon against infection.

METHODS

A mouse model of lung infection and a co-culture model of human bronchial epithelial cells with were established to explore the protective effect of AdipoRon. Liquid chromatography-mass spectrometry was used to detect the effect of AdipoRon on sphingosine level in lung of -infected mouse models.

RESULTS

The down-regulation of adiponectin and AdipoR1 in airway of bronchiectasis patients was linked to infection. By activating AdipoR1, AdipoRon reduced adherence on bronchial epithelial cells and protected cilia from damage in vitro. With the treatment of AdipoRon, the load of in lung significantly decreased, and peribronchial inflammatory cell infiltration was lessened in vivo. The reduced level of sphingosine in the airway of infected mice was replenished by AdipoRon, thus playing a protective role in the airway. Moreover, AdipoRon activated P-AMPKα/PGC1α, inhibited TLR4/P-NF-κB p65, and reduced expression of pro-apoptotic bax. However, the protective effect of AdipoRon on resisting infection was weakened when AdipoR1 was knocked down.

CONCLUSION

AdipoRon protects bronchial epithelial cells and lung by enhancing their resistance to infection. The mechanism might be modulating sphingosine metabolism and activating P-AMPKα/PGC1α while inhibiting TLR4/P-NF-κB p65.