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参与者，据报道，在体外，LPS通过TLR4刺激肥大细胞产生Th2细胞因子，但在体内的研究仍有待进行。因此，我们研究了LPS对小鼠变应性鼻炎模型诱发期的影响。结果，在小鼠变应性鼻炎模型中，LPS加重了i型过敏反应的诱发期。此外，C3H/HeN小鼠的打喷嚏率在单独注射OVA和注射LPS的OVA小鼠中存在显著差异，但在tlr4缺陷的天然突变体C3H/HeJ小鼠中没有发现这种差异。C3H/HeN小鼠的嗜酸性粒细胞浸润在OVA和LPS刺激下比单独刺激的小鼠更为明显。western blot结果显示，两组小鼠IL-5、IL-10、IL-13均有表达，但IL-5在OVA和LPS攻毒小鼠中表达上调。然而，C3H/HeJ小鼠的嗜酸性粒细胞浸润和Th2细胞因子表达在单独孵育OVA与LPS孵育OVA之间无显著差异。综上所述，LPS可加重鼻症状，通过TLR4上调肥大细胞Th2细胞因子的产生。在未来的研究中，TLR4的可溶性形式应该被研究为变应性鼻炎小鼠模型和变应性鼻炎患者的有希望的治疗选择之一。

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.