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Modulation of murine allergic rhinosinusitis by CpG oligodeoxynucleotides.

机译:CpG寡脱氧核苷酸对鼠类变应性鼻鼻窦炎的调节作用。

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BACKGROUND Allergic rhinosinusitis is characterized by eosinophilic inflammation of the upper airway, which is induced by TH-2 cytokines. CpG oligodeoxynucleotides (ODN) are known to induce TH-1 and to suppress TH-2 cytokines in a variety of settings, including murine models of asthma.OBJECTIVE To examine the effect of CpG ODN in a murine model of upper airway allergic inflammation and to correlate with reduction of its manifestations of sneezing and nasal scratching.METHODS BALB/c mice were sensitized using Ovalbumin (Ova) intraperitoneally and challenged with aerosolized Ova. CpG ODN were administered at the time of Ova sensitization. Outcomes measured included nasal symptoms, submucosal eosinophilia in the areas lined by respiratory or olfactory epithelium, and bone marrow eosinophilia. To delineate the mechanism of CpG ODN-induced suppression of eosinophilic inflammation, in vitro experiments were carried out to examine the effect of stimulation with Ova on splenocytes obtained from mice that were treated with CpG or control ODN (or no ODN) in vivo. Supernatant was collected after 72 hours of incubation and cytokines were measured by enzyme linked immunosorbent assay.RESULTS CpG ODN administered at the time of Ova sensitization effectively abrogated nasal symptoms and eosinophilic upper airway inflammation compared with mice treated with control ODN or with no ODN. Cytokine data revealed that Ova sensitization suppressed IFN-gamma and induced IL-4 and IL-5 compared with non-sensitized mice. CpG ODN treatment reversed these effects.CONCLUSION CpG ODN prevents the development of TH-2-mediated eosinophilic inflammation and symptoms in a murine model of allergic rhinosinusitis.
机译:背景技术变应性鼻-鼻窦炎的特征在于由TH-2细胞因子诱导的上呼吸道嗜酸性炎症。已知CpG寡脱氧核苷酸(ODN)在包括哮喘小鼠模型在内的各种环境中均可诱导TH-1并抑制TH-2细胞因子。目的研究CpG ODN在上呼吸道过敏性炎症小鼠模型中的作用与减少打喷嚏和鼻抓挠的表现相关。方法将BALB / c小鼠腹腔内用卵清蛋白(Ova)致敏并用雾化的Ova攻击。在Ova致敏时给予CpG ODN。测量的结果包括鼻部症状,在呼吸或嗅觉上皮衬里的区域的粘膜下嗜酸性粒细胞增多和骨髓嗜酸性粒细胞增多。为了描述CpG ODN诱导的嗜酸性粒细胞炎症抑制的机制,进行了体外实验,以研究Ova刺激对从体内经CpG或对照ODN(或无ODN)治疗的小鼠获得的脾细胞的影响。温育72小时后收集上清液,并通过酶联免疫吸附测定法测定细胞因子。结果与对照ODN或无ODN治疗的小鼠相比,在卵敏化时给予CpG ODN可有效消除鼻部症状和嗜酸性上呼吸道炎症。细胞因子数据显示,与未敏化的小鼠相比,卵子敏化可抑制IFN-γ并诱导IL-4和IL-5。结论CpG ODN可预防变应性鼻-鼻窦炎小鼠模型中TH-2介导的嗜酸性炎症和症状的发展。

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