Epigenetic changes: An emerging potential pharmacological target in allergic rhinitis.
Epigenetic changes: An emerging potential pharmacological target in allergic rhinitis
The importance of epigenetics has increased due to identification of its role in the pathophysiology of a number of diseases including allergic rhinitis. Amongst the different epigenetic changes in allergic retinitis, deacetylation of histone proteins by histone deacetylase (HDACs), hypermethylation of DNA by DNA methyltransferases (DNMT) and alteration in post-transcriptional process by the changes in the levels of miRNA are widely studied.
Studies conducted related to allergic rhinitis have shown the elevation in the levels of HDAC1, 3 and 11 in the nasal epithelia and HDAC inhibitors have shown effectiveness in decreasing the symptoms of rhinitis. Their beneficial effects are attributed to restoration of the expression of TWIK-related potassium channel-1, correction of cytokine profile along with normalization of Th1/Th2 imbalance. Another epigenetic change due to increase in DNMT activity may induce DNA hypermethylation in CpG sites in the airway epithelial cells and CD4+ T-cells. The reduction in DNA methylation decreases allergic symptoms and normalizes the over-reactive immune system. Mechanistically, allergens may promote the hypermethylation in the promoter region of IFN-γ gene in CD4+ T cells via activation of ERK pathway to decrease the expression of IFN-γ. In allergic rhinitis patients, there is also a downregulation of certain miRNAs including miR-135a, miR-146a, miR-181a, miR-155 and upregulation of miRNA19a. This review discusses the studies describing the epigenetic changes taking place in the host cells in response to allergen along with possible mechanisms.