The role and mechanism of quercetin via TLR4/MyD88/IRAK4 signaling pathway in the treatment of allergic rhinitis

Abstract

Abstract An ovalbumin (OVA)-induced allergic rhinitis (AR) mouse model was established to investigate whether quercetin (QUE) treats AR via TLR4/MyD88/IRAK4 signaling pathway. SPF grade Balb/c mice were randomly divided into 4 groups: normal control (NC), OVA, dexamethasone (DEX), and (QUE) groups. OVA and aluminum hydroxide [AL(OH)3] were injected intraperitoneally for basic sensitization and OVA was dripped into the nose for challenge to induce a mouse model of AR. The mice were scored by observing the behaviors of scratching, sneezing and runny nose to assess whether the modeling was successful. The treatment groups (DEX and QUE) were given the corresponding drugs for gavage treatment for 1 week after successful modeling, and the OVA and NC groups were treated with normal saline instead. The levels of OVA-IgE, IL-4, IL-13, IL-1β, IL-17 and IL-10 in serum were measured by enzyme-linked immunosorbent assay (ELISA); the changes of mice nasal mucosa were observed in hematoxylin-eosin (HE) stained histopathological sections; the relative expression levels of mRNA and protein of TLR4, MyD88, IRAK4, NF-κB in lung tissues were measured by quantitative real-time PCR (qPCR) and western blot, respectively; the changes in the percentages of regulatory T cells (Treg) and helper T cells 17 (Th17) in splenocytes were detected by flow cytometry. The results showed that the allergic symptoms scores were greater than 10 points and the expression levels of OVA-IgE, IL-4, IL-13, IL-1β and IL-17 in the serum increased and the expression level of IL-10 decreased in the OVA group compared with NC group. HE staining of the nasal cavity suggested detachment and necrosis of the nasal mucosa, tissue edema, and inflammatory cell infiltration in the OVA group. The relative expression levels of mRNA and protein of TLR4, MyD88, IRAK4, NF-κB in lung tissues were increased and the percentage of Treg cells decreased and the percentage of Th17 cells increased in splenocytes of the OVA group. Based on these results, we speculate that QUE may inhibit inflammatory responses and induce immune tolerance via TLR4/MyD88/IRAK4 signaling pathway in mice model of AR.