There is increasing evidence that inhaled multi-walled carbon nanotubes (MWCNTs) can have harmful effects on the respiratory system. Rodent studies suggest that individuals with asthma may be susceptible to the adverse pulmonary effects of MWCNTs. Asthma is an allergic lung disease characterized by a T_H2 immune response that results in chronic airway disease characterized by eosinophilic lung inflammation, airway mucous cell metaplasia, and airway fibrosis. Signal transducer and activator of transcription 6 (STAT6) is a transcription factor with multiple roles in T_H2 type inflammation. Herein we sought to examine the role of STAT6 in the exacerbation of house dust mite (HDM) allergen-induced allergic airway disease by MWCNTs. Male wild type (WT) and STAT6 knockout (Stat6 KO) mice were dosed via intranasal aspiration on days 0, 2, 4, 14, 16 and 18 with either vehicle, HDM extract, MWCNTs, or a combination of HDM and MWCNTs. Necropsy was performed on day 21 to collect bronchoalveolar lavage fluid (BALF), serum and lung tissue. MWCNTs exacerbated HDM-induced allergic endpoints, including eosinophilic lung inflammation, mucous cell metaplasia, and serum IgE levels. HDM-induced eosinophilic lung inflammation, mucous cell metaplasia, and serum IgE and exacerbation of these endpoints by MWCNTs were ablated in Stat6 KO mice. In addition, airway fibrosis was significantly increased by the combination of HDM and MWCNTs in WT mice but not in Stat6 KO mice. These findings provide new mechanistic insight by demonstrating a requirement for STAT6 in MWCNT-induced exacerbation of allergic respiratory disease.

越来越多的证据表明，吸入多壁碳纳米管（MWCNT）会对呼吸系统产生有害影响。啮齿动物研究表明，哮喘患者可能容易受到多壁碳纳米管对肺部的不良影响。哮喘是一种过敏性肺部疾病，其特征是 T _H 2 免疫反应，导致慢性气道疾病，其特征是嗜酸性肺部炎症、气道粘液细胞化生和气道纤维化。信号转导和转录激活因子 6 (STAT6) 是一种在 T _H 2 型炎症中具有多种作用的转录因子。在此，我们试图研究 STAT6 在 MWCNT 引起的屋尘螨 (HDM) 过敏原诱导的过敏性气道疾病恶化中的作用。雄性野生型 (WT) 和 STAT6 敲除 ( Stat6 KO) 小鼠在第 0、2、4、14、16 和 18 天通过鼻内抽吸给予媒介物、HDM 提取物、MWCNT 或 HDM 和 MWCNT 的组合。第21天进行尸检以收集支气管肺泡灌洗液(BALF)、血清和肺组织。MWCNT 加剧了 HDM 诱导的过敏终点，包括嗜酸性肺部炎症、粘液细胞化生和血清 IgE 水平。HDM 诱导的嗜酸性肺部炎症、粘液细胞化生和血清 IgE 以及 MWCNT 导致的这些终点的恶化在Stat6 KO 小鼠中被消除。此外，HDM 和 MWCNT 的组合在 WT 小鼠中显着增加了气道纤维化，但在Stat6 KO 小鼠中则没有。这些发现证明了 MWCNT 诱导的过敏性呼吸道疾病恶化中需要 STAT6，从而提供了新的机制见解。