Identification of Dysregulated microRNAs in the Lungs of Allergen‐challenged Mice

Abstract

microRNAs (miRs) are important regulators of gene expression that interact with the RNA‐induced silencing complex (RISC) in the cellular cytoplasm. miRs have been implicated in inflammatory diseases such as asthma. We utilized intranasal administration of synthetic complementary sequence anti‐miRs in mice to demonstrate interference of engagement of the let 7 miR with its target mRNAs. Bioinformatic analysis of let7 target mRNAs showed activity of the anti‐miR in lung tissue. To identify miRs involved in allergen‐induced pulmonary inflammation, we characterized house dust mite (HDM) allergen‐induced pulmonary inflammation models. Intranasal HDM administration in the absence of alum produced both an eosinophilic and neutrophilic airway inflammatory response that was suppressed by Dexamethasone. miR and mRNA profiling was assessed using nanostring and microarray in the acute HDM model and identified a number of dysregulated miRs. The expression of miRs in HDM‐challenged mice was compared to the mRNA pathway signature and suggested the potential involvement of multiple miRs in the pulmonary inflammatory response. Ongoing experiments are assessing the effects of anti‐miR inhibition of these miRs in HDM challenge models to support drug discovery activities for pulmonary disease applications.