七氟醚抑制小鼠过敏性气道炎症Th2反应和NLRP3表达
2019/01/09
摘要
背景：我们的同事已经证明七氟醚在小鼠过敏性气道炎症模型中的治疗作用显著，但其作用机制仍未明确。在本研究中，我们试图研究七氟醚对过敏性气道炎症消退的影响，并评估NLRP3或NLRP3炎症小体是否参与这一过程。
方法：用卵清蛋白(OVA) 致敏并攻毒雌性(C57BL/6)小鼠。然后让小鼠接受MCC950 (10 mg/kg； i.p.)或3%七氟醚。评价支气管肺泡灌洗液(BALF)中炎性细胞总数及分类、促炎性细胞因子、支气管周围炎症密度及粘液生成情况。此外，我们还分析了肺组织中NLRP3蛋白水平、细胞凋亡相关的含caspase活化和募集域(ASC)的斑点样蛋白、pro-caspase-1蛋白和caspase-1蛋白水平。
结果：我们发现七氟醚对卵清蛋白诱导的支气管周围炎性细胞招募、杯状细胞增生、血清IgE水平、炎性细胞、BALF中Th2细胞因子分泌均有明显的抑制作用，其抑制效果与MCC950治疗相当。此外，七氟醚与MCC950类似，可以明显抑制卵清蛋白诱导的肺组织中NLRP3蛋白活性。并且我们发现卵清蛋白致毒不能增加肺组织中ASC,pro-caspase-1和caspase-1的蛋白表达水平以及支气管肺泡灌洗液中IL-18和IL-1β的水平。
结论：综上所述，我们的数据显示七氟醚通过抑制Th2反应和NLRP3蛋白表达改善了过敏性气道炎症。独立于炎性小体的NLRP3蛋白参与了本模型过敏性哮喘的发病机制。
Sevoflurane Inhibits the Th2 Response and NLRP3 Expression in Murine Allergic Airway Inflammation.
Wang L, Zha B, Shen Q, Zou H, Cheng C, Wu H, Liu R.
Abstract
BACKGROUND: 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.
METHODS: 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.
RESULTS: 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-1β in BALF.
CONCLUSION: 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.
背景：我们的同事已经证明七氟醚在小鼠过敏性气道炎症模型中的治疗作用显著，但其作用机制仍未明确。在本研究中，我们试图研究七氟醚对过敏性气道炎症消退的影响，并评估NLRP3或NLRP3炎症小体是否参与这一过程。
方法：用卵清蛋白(OVA) 致敏并攻毒雌性(C57BL/6)小鼠。然后让小鼠接受MCC950 (10 mg/kg； i.p.)或3%七氟醚。评价支气管肺泡灌洗液(BALF)中炎性细胞总数及分类、促炎性细胞因子、支气管周围炎症密度及粘液生成情况。此外，我们还分析了肺组织中NLRP3蛋白水平、细胞凋亡相关的含caspase活化和募集域(ASC)的斑点样蛋白、pro-caspase-1蛋白和caspase-1蛋白水平。
结果：我们发现七氟醚对卵清蛋白诱导的支气管周围炎性细胞招募、杯状细胞增生、血清IgE水平、炎性细胞、BALF中Th2细胞因子分泌均有明显的抑制作用，其抑制效果与MCC950治疗相当。此外，七氟醚与MCC950类似，可以明显抑制卵清蛋白诱导的肺组织中NLRP3蛋白活性。并且我们发现卵清蛋白致毒不能增加肺组织中ASC,pro-caspase-1和caspase-1的蛋白表达水平以及支气管肺泡灌洗液中IL-18和IL-1β的水平。
结论：综上所述，我们的数据显示七氟醚通过抑制Th2反应和NLRP3蛋白表达改善了过敏性气道炎症。独立于炎性小体的NLRP3蛋白参与了本模型过敏性哮喘的发病机制。
(中日友好医院呼吸与危重症医学科 禹汶伯 摘译 林江涛 审校)
(J Immunol Res. 2018 Sep 30;2018.)
(J Immunol Res. 2018 Sep 30;2018.)
Sevoflurane Inhibits the Th2 Response and NLRP3 Expression in Murine Allergic Airway Inflammation.
Wang L, Zha B, Shen Q, Zou H, Cheng C, Wu H, Liu R.
Abstract
BACKGROUND: 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.
METHODS: 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.
RESULTS: 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-1β in BALF.
CONCLUSION: 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.
上一篇：
蒸煮过的干草对患重症哮喘的马临床症状及气道免疫反应的影响
下一篇：
补充维生素D降低交通相关颗粒物暴露的哮喘进展
