Toll-like receptor 9 (TLR9) has been reported to mediate airway inflammation, however, the underlying mechanism is poorly understood. In the present study, our objective was to reveal whether TLR9 regulates NLRP3 inflammasome and oxidative stress in murine allergic airway inflammation and Raw264.7 cells. Female wild type(WT)and TLR9^−/−mice on C57BL/6 background were used to induce allergic airway inflammation by challenge of OVA, and Raw264.7 cells with or without TLR9 knockdown by small interfering RNA (siRNA) were stimulated by S.aureus. The results demonstrated that deletion of TLR9 effectively attenuated OVA-induced allergic airway inflammation including inflammatory cells infiltration and goblet cell hyperplasia. Meanwhile, OVA-induced protein expression of NLRP3, caspase-1(p20) and mature IL-1β, as well as secretion of IL-1β and IL-18 in wild type mice (WT) was obviously suppressed by TLR9 deficiency. Concomitantly, the expression of oxidative markers 8-OhDG and nitrotyrosine was increased in OVA-challenged WT mice, while TLR9 deficiency significantly inhibited such increase. Similarly, in the in vitro study, we found that knockdown of TLR9 markedly suppressed S.aureus-induced activation of NLRP3 inflammasome and oxidative stress in Raw264.7 cells. Collectively, our findings indicated that TLR9 may mediate allergic airway inflammation via activating NLRP3 inflammasome and oxidative stress.

据报道，Toll样受体9（TLR9）介导气道炎症，但是，其潜在机制尚不清楚。在本研究中，我们的目的是揭示TLR9是否调节鼠变应性气道炎症和Raw264.7细胞中的NLRP3炎性体和氧化应激。用C57BL / 6背景的雌性野生型（WT）和TLR9 ^-/-小鼠通过OVA攻击诱导过敏性气道炎症，并通过S刺激带有或不带有小干扰RNA（siRNA）的TLR9敲低的Raw264.7细胞。金黄色葡萄球菌。结果表明，TLR9的删除可有效减轻OVA诱导的过敏性气道炎症，包括炎症细胞浸润和杯状细胞增生。同时，TLR9缺乏明显抑制了OVA诱导的野生型小鼠野生型NLRP3，caspase-1（p20）和成熟IL-1β的蛋白表达以及IL-1β和IL-18的分泌。伴随地，在OVA攻击的WT小鼠中，氧化标记物8-OhDG和硝基酪氨酸的表达增加，而TLR9缺乏明显抑制了这种增加。同样，在体外研究中，我们发现TLR9的敲低显着抑制了金黄色葡萄球菌-在Raw264.7细胞中诱导NLRP3炎性小体活化和氧化应激。总的来说，我们的发现表明TLR9可能通过激活NLRP3炎性体和氧化应激来介导过敏性气道炎症。