Sirtuins as novel targets in the pathogenesis of airway inflammation in bronchial asthma.

ABSTRACT

Sirtuins are NAD-dependent class III histone deacetylase, which modulate the epigenetic changes to influence the functions in normal and diseased conditions. Preclinical studies have described an increase in the levels of sirtuin 2 and decrease in the levels of sirtuin 6 in the lungs. Sirtuin 2 exerts proinflammatory actions and hence, its blockers reduce the airway inflammation and symptoms of asthma. On the other hand, sirtuin 6 is anti-inflammatory and its activators produce beneficial actions in asthma. The beneficial effects of sirtuin 6 have been attributed to decrease in acetylation of transcriptional factor GATA3 in the T cells, which is associated with decrease in the TH2 immune response. However, there seems to be dual role of sirtuin 1 in airway inflammation as its proinflammatory as well as anti-inflammatory actions have been described in asthma. The anti-inflammatory actions of sirtuin 1 have been attributed to decrease in acetylation of GATA3 and inhibition of Akt/NF-kappaB signaling. On the other hand, proinflammatory actions of sirtuin 1 have been attributed to increase in the expression of HIF-1α and VEGF along with repression of PPAR-γ activity. The present review discusses the role of different sirtuins in the pathogenesis of bronchial asthma. Moreover, it also discusses sirtuin-triggered signaling pathways that may contribute in modulating the disease state of bronchial asthma.