downregulation of allergic rhinitis with a modification of mast cells In relation with toll-like receptors

肥大细胞是变应性鼻炎诱发期的关键细胞，已有报道在体外通过TLR4在脂多糖的刺激下产生Th2细胞因子，但体内研究仍未完成。因此，我们研究了内毒素对小鼠变应性鼻炎模型诱导期的影响。结果，在小鼠变应性鼻炎模型中，脂多糖加重了I型变态反应的诱发阶段。此外，在单独用OVA攻击和OVA加脂多糖攻击的C3H/HEN小鼠中，打喷嚏的发生率有显著差异，但在TLR4缺乏的自然突变的C3H/HeJ小鼠中没有检测到这种差异。与单纯OVA组相比，OVA+LPS组小鼠的嗜酸性粒细胞浸润更为明显。免疫印迹分析显示，两组小鼠均有IL-5、IL-10、IL-13的表达，但OVA和内毒素诱导的小鼠IL-5表达上调。然而，OVA单独攻击和OVA+LPS攻击的C3H/HeJ小鼠在嗜酸性粒细胞浸润和Th2细胞因子的表达上没有显著差异。这些数据综合起来表明，内毒素加重了鼻部症状，通过TLR4上调肥大细胞Th2细胞因子的产生。在未来的一项研究中，TLR4的可溶性形式应该被检验为变应性鼻炎小鼠模型和变应性鼻炎患者的有前景的治疗选择之一。

Mast cells which is the key player at the eliciting phase of allergic rhinitis, have been reported to produce Th2 cytokines in vitro with LPS stimulation via TLR4, but in vivo study remains to be performed. Therefore, we investigated the LPS effect on the eliciting phase of murine allergic rhinitis model. As a result, LPS aggravated the eliciting phase of type-I allergic reaction, in a murine allergic rhinitis model. Furthermore, the significant difference in sneezing rates between C3H/HeN mice challenged with OVA alone and OVA with LPS was found, but this difference was not detected in C3H/HeJ mice, which are TLR4-deficient natural mutants . Eosinophil infiltration was more prominent in C3H/HeN mice challenged with OVA and LPS, in comparison with those in mice challenged with OVA alone. In western blot analysis, IL-5,IL-10,IL-13 expression was seen in both groups, but IL-5 expession was upregulated in mice challenged with OVA and LPS. However, there was no significant difference in eosinophil infiltration and Th2 cytokine expression between C3H/HeJ mice challenged with OVA alone and OVA with LPS. These data taken together suggests that LPS aggravates nasal symptom, upregulating Th2 cytokine production of mast cells via TLR4. In a future study, soluble form of TLR4 should be examined to be one of promising treatment options in a murine model of allergic rhinitis and patients with allergic rhinitis as well.