Department of Pulmonary, Anhui Geriatric Institute, The First Affiliated Hospital of Anhui Medical University, Jixi Road 218, Hefei, Anhui 230022, China.
Department of Anesthesiology, The First Affiliated Hospital of Anhui Medical University, Jixi Road 218, Hefei, Anhui 230022, China.
J Immunol Res. 2018 Sep 30;2018:9021037. doi: 10.1155/2018/9021037. eCollection 2018.
Our colleagues have demonstrated an impressive therapeutic role of sevoflurane in a murine allergic airway inflammation model, but the mechanisms underlying this effect remain undefined. In this study, we tried to investigate the effect of sevoflurane on the resolution of allergic airway inflammation and to assess whether NLRP3 or the NLRP3 inflammasome is involved in this process.
Female (C57BL/6) mice were sensitized and challenged with ovalbumin (OVA). Then, some of the mice received MCC950 (10 mg/kg; i.p.) or 3% sevoflurane. Total and differential inflammatory cell numbers, proinflammatory cytokines in bronchoalveolar lavage fluid (BALF), the peribronchial inflammation density, and mucus production were evaluated. In addition, we analysed the protein levels of NLRP3, the apoptosis-associated speck-like protein containing the caspase activation and recruitment domain (ASC), pro-caspase-1, and caspase-1 in the lung tissue.
We found that OVA-induced inflammatory cell recruitment to peribronchial regions, goblet cell hyperplasia, the serum levels of IgE, inflammatory cells, and the Th2 cytokine secretion in BALF was potently suppressed by sevoflurane with an efficacy comparable with that suppressed by MCC950 treatment. Furthermore, sevoflurane, similar to MCC950, clearly inhibited the OVA-induced activity of NLRP3 in the lungs. In addition, we found that OVA challenge failed to increase the expression of ASC, pro-caspase-1, and caspase-1 in the lungs and the levels of IL-18 and IL-1 in BALF.
Taken together, our data showed that sevoflurane ameliorated allergic airway inflammation by inhibiting Th2 responses and NLRP3 expression. The NLRP3 independent of inflammasomes participated in the pathogenesis of allergic asthma in this model.
我们的同事已经证明七氟醚在小鼠变应性气道炎症模型中具有令人印象深刻的治疗作用，但这种作用的机制尚不清楚。在这项研究中，我们试图研究七氟醚对变应性气道炎症消退的影响，并评估 NLRP3 或 NLRP3 炎性体是否参与这一过程。
雌性（C57BL/6）小鼠用卵清蛋白（OVA）致敏和攻击。然后，一些小鼠接受 MCC950（10mg/kg；腹腔注射）或 3%七氟醚。评估支气管肺泡灌洗液（BALF）中的总细胞和分类细胞数、促炎细胞因子、支气管周围炎症密度和黏液生成。此外，我们还分析了肺组织中 NLRP3、凋亡相关斑点样蛋白含有半胱氨酸蛋白酶激活和募集结构域（ASC）、前半胱天冬酶-1 和半胱天冬酶-1 的蛋白水平。
我们发现，OVA 诱导的炎症细胞募集到支气管周围区域、杯状细胞增生、血清 IgE 水平、炎症细胞和 BALF 中 Th2 细胞因子的分泌，均被七氟醚强烈抑制，其疗效与 MCC950 治疗相当。此外，七氟醚与 MCC950 相似，明显抑制了 OVA 诱导的肺部 NLRP3 活性。此外，我们发现，OVA 攻击未能增加肺部 ASC、前半胱天冬酶-1 和半胱天冬酶-1 的表达，以及 BALF 中 IL-18 和 IL-1 的水平。
综上所述，我们的数据表明，七氟醚通过抑制 Th2 反应和 NLRP3 表达来改善变应性气道炎症。NLRP3 炎性体在该模型中的过敏性哮喘发病机制中起作用。
