屋尘螨诱导的气道炎症的小鼠模型肺中的单核细胞白介素-33
2016/08/31
摘要
背景：白细胞介素33（IL-33）激活组2先天淋巴细胞（ILC2），导致支气管哮喘T- 辅助细胞 -2炎症。细胞凋亡和坏死过程中气道上皮细胞是IL-33的来源。然而，IL-33通常被认为是来源于诸如白细胞，而不是来源于气道上皮细胞，并且IL-33产生和释放的机制尚不完全清楚。本研究的目的是通过气道炎症单核细胞阐明IL-33产生的作用。
方法：BALB/c小鼠应用屋尘螨（HDM）致敏和激发。通过对支气管肺泡灌洗液（BAL）中的炎性细胞进行计数，以及对肺中的IL-25、IL-33和胸腺基质淋巴细胞（TSLP）水平进行定量来评估气道炎症。在肺切片中免疫组化测定IL-33。流式细胞仪检测Ly6C，CD11b和CD11c的表达。氯膦酸二钠脂质体用于HDM气道炎症模型来消耗循环的单核细胞。
结果：与对照组小鼠相比，HMD小鼠中的IL-33，而不是IL-25或TSLP，在肺组织匀浆中的水平明显升高。用免疫组化对肺IL-33-阳性细胞进行鉴定，发现在支气管和血管周围面积增加。此外，与对照组相比，来自HDM小鼠肺组织的单核细胞中IL-33水平增多。Ly6c在HDM组单核细胞中的表达显著高于对照组。用氯膦酸二钠脂质体处理不仅降低支气管肺泡灌洗液中的炎症细胞、气道高反应性和肺Th2型细胞因子，而且降低肺中IL-33。
结论：源自肺单核细胞中的IL-33可能参与HDM诱导的气道炎症的发病。
（杨冬 审校）
PLoS One. 2016 Jun 16;11(6):e0157571. doi: 10.1371/journal.pone.0157571. eCollection 2016.
Interleukin-33 from Monocytes Recruited to the Lung Contributes to House Dust Mite-Induced Airway Inflammation in a Mouse Model.
Tashiro H1, Takahashi K1, Hayashi S1, Kato G1, Kurata K2, Kimura S1, Sueoka-Aragane N1.
Author information
Abstract
BACKGROUND:Interleukin-33 (IL-33) activates group 2 innate lymphoid cells (ILC2), resulting in T-helper-2 inflammation in bronchial asthma. Airway epithelial cells were reported as sources of IL-33 during apoptosis and necrosis. However, IL-33 is known to be from sources other than airway epithelial cells such as leukocytes, and the mechanisms of IL-33 production and release are not fully understood. The aim of this study was to clarify the role of IL-33 production by monocytes in airway inflammation.
METHODS:BALB/c mice were sensitized and challenged with a house dust mite (HDM) preparation. Airway inflammation was assessed by quantifying inflammatory cells in bronchoalveolar lavage (BAL) fluid, and IL-25, IL-33, and thymic stromal lymphopoietin (TSLP) levels in lung. Immunohistochemistry for IL-33 in lung sections was also performed. Ly6c, CD11b, and CD11c expression was examined by flow cytometry. Clodronate liposomes were used in the HDM-airway inflammation model to deplete circulating monocytes.
RESULTS:The IL-33, but not IL-25 or TSLP, level in lung homogenates was markedly increased in HDM mice compared to control mice. IL-33-positive cells in the lungs were identified using immunohistochemistry and were increased in areas surrounding bronchi and vasculature. Furthermore, IL-33 levels were increased in mononuclear cells derived from lungs of HDM mice compared to controls. The expression of Ly6c in mononuclear cells was significantly higher in HDM mice than in controls. Treatment with clodronate liposomes led to inhibition of not only inflammatory cells in BAL fluid, airway hyper reactivity and Th2 cytokines in lung, but also IL-33 in lung.
CONCLUSION:IL-33 from monocytes recruited to the lung may contribute to the pathogenesis of HDM-induced airway inflammation.
PLoS One. 2016 Jun 16;11(6):e0157571. doi: 10.1371/journal.pone.0157571. eCollection 2016.
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在过敏性哮喘和鼻炎小鼠模型中的慢性超重独立效应
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循环MicroRNAs：与哮喘肺功能的关系
