Effects of anticholinergic agent on miRNA profiles and transcriptomes in a murine model of allergic rhinitis

摘要

Anticholinergic agent, ipratropium bromide (IB) ameliorates symptoms of allergic rhinitis (AR) using neuroimmunologic mechanisms. However, the underlying molecular mechanism remains largely unclear. In the present study, 27 mice with AR induced by ovalbumin were randomly allocated to one of three groups: Model group, model group with IB treatment for 2 weeks, and model group with IB treatment for 4 weeks. Allergic symptoms were evaluated according to symptoms scores. Differentially expressed genes [microRNAs (miRNAs) and messenger RNAs (mRNAs)] of nasal mucosa were identified by microarray analysis. The expression levels of candidate genes were measured by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The data indicates that the symptoms scores in allergic mice were significantly reduced by IB treatment. In the nasal mucosa of allergic mice with IB treatment, 207 mRNAs and 87 miRNAs were differentially expressed, when compared with the sham group. IB treatment significantly downregulated the expression levels of interleukin-4R alpha and prostaglandin D2 synthase, whereas the leukemia inhibitory factor, A20 and nuclear receptor subfamily 4, group A, member 1 expression levels were upregulated. Similarly, the expression levels of mmu-miR-124-3p/5p, -133b-5p, -133a-3p/ 5p, -384-3p, -181a-5p, -378a-5p and -3071-5p were significantly increased. RT-qPCR data further validated these mRNA and miRNA expression levels. Thus, IB treatment regulated expression of allergic immune-associated mRNAs and miRNAs of the nasal mucosa in allergic mice, which may be associated with ameliorated nasal allergic symptoms.