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

Abstract

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-4Rα 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.

Cholinergic neuron‐like D‐U87 cells promote polarization of allergic rhinitis T‐helper 2 cells

“…In our previous studies, nasal vidian neurectomy achieved a good therapeutic effect in patients with refractory AR, and IB has been shown to reverse the nasal mucosal Th2 advantage in BALB/c mice. 6,14,15 Similar to our previous studies, in the present in-vitro neuroimmune coculture study, D-U87 neurons promoted the polarization of CD4 + T cells from patients with AR toward Th2 cells, and the increased percentage of Th2 cells was then reduced by IB treatment. Interestingly, in contrast to observations in cells from patients with AR, CD4 + T cells from healthy controls polarized into Th1 cells after coculture with D-U87 neurons.…”

“…Most clinical investigations and animal studies have revealed an important role for nerves in AR , ; however, controversy exists regarding whether parasympathetic nerves exert an effect on immune regulation. In our previous studies, nasal vidian neurectomy achieved a good therapeutic effect in patients with refractory AR, and IB has been shown to reverse the nasal mucosal Th2 advantage in BALB/c mice , , . Similar to our previous studies, in the present in‐vitro neuroimmune coculture study, D‐U87 neurons promoted the polarization of CD4 + T cells from patients with AR toward Th2 cells, and the increased percentage of Th2 cells was then reduced by IB treatment.…”

“…Posterior nasal neurectomy has been shown to lead to decreases in IL‐5 and mast cells in severe AR . Our previous studies showed that inhibition of cholinergic nerve hyperactivity using ipratropium bromide (IB), a nonselective muscarinic cholinergic receptor inhibitor, decreased expression of IL‐4 mRNA in the nasal mucosa of BALB/c mice , . However, in a recent study, Nishijima et al reported that the expression of IL‐4 and interferon‐γ (IFN‐γ) mRNAs was not altered in the nasal mucosa of Sprague‐Dawley rats after nasal posterior neurectomy .…”

“…13 Our previous studies showed that inhibition of cholinergic nerve hyperactivity using ipratropium bromide (IB), a nonselective muscarinic cholinergic receptor inhibitor, decreased expression of IL-4 mRNA in the nasal mucosa of BALB/c mice. 14,15 However, in a recent study, Nishijima et al reported that the expression of IL-4 and interferon-γ (IFN-γ ) mRNAs was not altered in the nasal mucosa of Sprague-Dawley rats after nasal posterior neurectomy. 16 The discrepancy between these studies may be explained by the use of different research methods.…”

Acupuncture for the treatment of allergic rhinitis

“…[5–7] Nasal glucocorticoids is currently the most effective drugs for the treatment of AR, for patients with bronchial asthma, can be conducive to asthma control and improve lung function. [8,9] Other drugs, including antihistamines, [10] antileukotrienes, [11] mast cell membrane stabilizers, [12] decongestants, [13] and anticholinergics, [14] are also commonly used. Allergen-specific immunotherapy has short-term and long-term effects on AR, preventing the development of asthma and reducing new sensitization.…”