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可吸入的微米和纳米聚苯乙烯颗粒在肺部疾病发病机制中引发的无菌性炎症。

Sterile inflammation induced by respirable micro and nano polystyrene particles in the pathogenesis of pulmonary diseases.

作者信息

Antonio Laganà, Visalli Giuseppa, Facciolà Alessio, Saija Caterina, Bertuccio Maria Paola, Baluce Barbara, Celesti Consuelo, Iannazzo Daniela, Di Pietro Angela

机构信息

Department of Biomedical and Dental Sciences and Morphofunctional Imaging, University of Messina, Via Consolare Valeria, 98125 Messina, Italy.

Istituto Clinico Polispecialistico C.O.T. Cure Ortopediche Traumatologiche s.p.a., Viale Italia, 98124 Messina, Italy.

出版信息

Toxicol Res (Camb). 2024 Sep 2;13(5):tfae138. doi: 10.1093/toxres/tfae138. eCollection 2024 Oct.

Abstract

Sterile inflammation is involved in the lung pathogenesis induced by respirable particles, including micro- and nanoplastics. Their increasing amounts in the ambient and in indoor air pose a risk to human health. In two human cell lines (A549 and THP-1) we assessed the proinflammatory behavior of polystyrene nanoplastics (nPS) and microplastics (mPS) (Ø 0.1 and 1 μm). Reproducing environmental aging, in addition to virgin, the cells were exposed to oxidized nPS/mPS. To study the response of the monocytes to the inflammatory signal transmitted by the A549 through the release of soluble factors (e.g. alarmins and cytokines), THP-1 cells were also exposed to the supernatants of previously nPS/mPS-treated A549. After dynamic-light-scattering (DLS) analysis and protein measurements for the assessment of protein corona in nPS/mPS, real-time PCR and enzyme-linked-immunosorbent (ELISA) assays were performed in exposed cells. The pro-inflammatory effects of v- and ox-nPS/mPS were attested by the imbalance of the Bax/Bcl-2 ratio in A549, which was able to trigger the inflammatory cascade, inhibiting the immunologically silent apoptosis. The involvement of NFkB was confirmed by the overexpression of p65 after exposure to ox-nPS and v- and ox-mPS. The fast and higher levels of IL-1β, only in THP-1 cells, underlined the NLPR3 inflammasome activation.

摘要

无菌性炎症参与了可吸入颗粒(包括微塑料和纳米塑料)诱导的肺部发病机制。它们在环境和室内空气中的含量不断增加,对人类健康构成风险。在两种人类细胞系(A549和THP-1)中,我们评估了聚苯乙烯纳米塑料(nPS)和微塑料(mPS)(直径0.1和1微米)的促炎行为。除了原始塑料外,为模拟环境老化,细胞还暴露于氧化的nPS/mPS中。为了研究单核细胞对A549通过释放可溶性因子(如警报素和细胞因子)传递的炎症信号的反应,THP-1细胞也暴露于先前经nPS/mPS处理的A549的上清液中。在对nPS/mPS进行动态光散射(DLS)分析和蛋白质测量以评估蛋白质冠层后,对暴露的细胞进行实时PCR和酶联免疫吸附(ELISA)测定。v-nPS/mPS和ox-nPS/mPS的促炎作用通过A549中Bax/Bcl-2比值的失衡得到证实,这能够触发炎症级联反应,抑制免疫沉默的细胞凋亡。暴露于ox-nPS以及v-mPS和ox-mPS后p65的过表达证实了NFkB的参与。仅在THP-1细胞中快速且高水平的IL-1β突出了NLPR3炎性小体的激活。

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