SIRT5 Alleviated Eosinophilic Asthma Through ROS Inhibition and Nrf2/HO-1 Activation.

Asthma is a prevalent chronic disease with high morbidity and mortality in both children and adults, imposing a burden on the physical and mental well-being of patients, as well as their families. Inhaled corticosteroids and long-acting β2 agonists are mostly used to control asthma, these therapies are not suitable for patients with severe asthma. Approximately 80% of severe uncontrolled asthma cases are classified as eosinophilic asthma (EA). Oxidative stress and inflammation play crucial roles in the pathology and development of asthma, with SIRT5 being important in the process of anti-oxidation and anti-inflammation. However, little is known about the role of SIRT5 in EA and its regulatory mechanism on substrate protein and biological function. In this study, we investigated the role of SIRT5 in ovalbumin (OVA)-induced EA mouse models and house dust mite (HDM)-induced asthmatic cell models, while exploring its potential mechanisms. We found that SIRT5 alleviated EA by inhibiting reactive oxygen species and activating Nrf2/HO-1 pathways. Interestingly, overexpression of SIRT5 attenuated the inflammatory response in EA. Taken together, these results suggest that SIRT5 may serve as a promising target for managing asthma symptoms.