Kim Byeong Gon, Lee Pureun Haneul, Lee Sun Hye, Park Moo Kyun, Jang An Soo
Division of Allergy and Respiratory Medicine, Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Bucheon, Korea.
Department of Otolayngology, Seoul National Uiversity, Seoul, Korea.
Allergy Asthma Immunol Res. 2017 May;9(3):257-264. doi: 10.4168/aair.2017.9.3.257.
Nanoparticles (NPs) may cause cell and tissue damage, leading to local and systemic inflammatory responses and adverse effects on health due to the inhalation of particulate matter. The inflammasome is a major regulator of inflammation through its activation of pro-caspase-1, which cleaves pro-interleukin-1β (pro-IL-1β) into its mature form and may induce acute and chronic immune responses to NPs. However, little is known about the response of the inflammasome to NP exposure via the airways in asthma. The aim of this study was to identify the impact of titanium dioxide (TiO₂) NPs on inflammasome in a mouse model of allergic asthma.
Mice were treated with ovalbumin (OVA) or TiO₂ NPs. IL-1β, IL-18, NAIP, CIITA, HET-E, TP-2 (NACHT), leucine-rich repeat (LRR), pyrin domain-containing protein 3 (NLRP3), and caspase-1 were assessed by Western blotting. Caspase-1 was assessed by immunohistochemistry (IHC). Levels of reactive oxygen species (ROS)-as markers of oxidative damage-and the mediators 8-isoprostane and carbonyl were measured by enzyme-linked immunosorbent assay (ELISA).
Airway hyperresponsiveness (AHR) and inflammation were increased in OVA-sensitized/challenged mice, and these responses were exacerbated by exposure to TiO₂ NPs. NP treatment increased IL-1β and IL-18 expression in OVA-sensitized/challenged mice. NPs augmented the expression of NLRP3 and caspase-1, leading to production of active caspase-1 in the lung. Caspase-1 expression was increased and exacerbated by TiO₂ NP exposure in OVA-sensitized/challenged mice. ROS levels tended to be increased in OVA-sensitized/challenged and OVA-sensitized/challenged-plus-TiO₂ NP-exposed mice.
Our data demonstrated that inflammasome activation occured in asthmatic lungs following NP exposure, suggesting that targeting the inflammasome may assist in controling NP-induced airway inflammation and hyperresponsiveness.
纳米颗粒（NPs）可能导致细胞和组织损伤，由于吸入颗粒物而引发局部和全身炎症反应并对健康产生不利影响。炎性小体是炎症的主要调节因子，它通过激活前半胱天冬酶-1发挥作用，前半胱天冬酶-1将前白细胞介素-1β（pro-IL-1β）切割成其成熟形式，并可能诱导对NPs的急性和慢性免疫反应。然而，关于哮喘患者气道暴露于NPs时炎性小体的反应知之甚少。本研究的目的是在过敏性哮喘小鼠模型中确定二氧化钛（TiO₂）纳米颗粒对炎性小体的影响。
用卵清蛋白（OVA）或TiO₂纳米颗粒处理小鼠。通过蛋白质免疫印迹法评估白细胞介素-1β、白细胞介素-18、NAIP、CIITA、HET-E、TP-2（NACHT）、富含亮氨酸重复序列（LRR）、含pyrin结构域蛋白3（NLRP3）和半胱天冬酶-1。通过免疫组织化学（IHC）评估半胱天冬酶-1。通过酶联免疫吸附测定（ELISA）测量作为氧化损伤标志物的活性氧（ROS）水平以及介质8-异前列腺素和羰基的水平。
OVA致敏/激发小鼠的气道高反应性（AHR）和炎症增加，并且暴露于TiO₂纳米颗粒会加剧这些反应。纳米颗粒处理增加了OVA致敏/激发小鼠中白细胞介素-1β和白细胞介素-18的表达。纳米颗粒增强了NLRP3和半胱天冬酶-1的表达，导致肺中活性半胱天冬酶-1的产生。在OVA致敏/激发小鼠中，TiO₂纳米颗粒暴露增加并加剧了半胱天冬酶-1的表达。在OVA致敏/激发和OVA致敏/激发加TiO₂纳米颗粒暴露的小鼠中，ROS水平倾向于升高。
我们的数据表明，在暴露于纳米颗粒后，哮喘小鼠的肺部发生了炎性小体激活，这表明靶向炎性小体可能有助于控制纳米颗粒诱导的气道炎症和高反应性。
