School of Public Health, Xinxiang Medical University, Xinxiang 453003, PR China.
Henan Provincial Key Laboratory of Animal Immunology, Henan Academy of Agricultural Sciences, Zhengzhou 450002, PR China.
Ecotoxicol Environ Saf. 2023 Jul 1;259:115069. doi: 10.1016/j.ecoenv.2023.115069. Epub 2023 May 25.
Exposure to particulate matter (PM) has been associated with increased hospital admissions for influenza. Airway epithelial cells are a primary target for inhaled environmental insults including fine PM (PM) and influenza viruses. The potentiation of PM exposure on the effects of influenza virus on airway epithelial cells has not been adequately elucidated. In this study, the effects of PM exposure on influenza virus (H3N2) infection and downstream modulation of inflammation and antiviral immune response were investigated using a human bronchial epithelial cell line, BEAS-2B. The results showed that PM exposure alone increased the production of pro-inflammatory cytokines including interleukin-6 (IL-6) and IL-8 but decreased the production of the antiviral cytokine interferon-β (IFN-β) in BEAS-2B cells while H3N2 exposure alone increased the production of IL-6, IL-8, and IFN-β. Importantly, prior exposure to PM enhanced subsequent H3N2 infectivity, expression of viral hemagglutinin protein, as well as upregulation of IL-6 and IL-8, but reduced H3N2-induced IFN-β production. Pre-treatment with a pharmacological inhibitor of nuclear factor-κB (NF-κB) suppressed pro-inflammatory cytokine production induced by PM, H3N2, as well as PM-primed H3N2 infection. Moreover, antibody-mediated neutralization of Toll-like receptor 4 (TLR4) blocked cytokine production triggered by PM or PM-primed H3N2 infection, but not H3N2 alone. Taken together, exposure to PM alters H3N2-induced cytokine production and markers of replication in BEAS-2B cells, which in turn are regulated by NF-κB and TLR4.
暴露于颗粒物（PM）已与流感住院人数增加有关。气道上皮细胞是吸入性环境刺激物（包括细颗粒物（PM）和流感病毒）的主要靶标。PM 暴露对流感病毒对气道上皮细胞的影响的增强作用尚未得到充分阐明。在这项研究中，使用人支气管上皮细胞系 BEAS-2B 研究了 PM 暴露对流感病毒（H3N2）感染以及炎症和抗病毒免疫反应的下游调节的影响。结果表明，PM 单独暴露会增加促炎细胞因子（包括白细胞介素 6（IL-6）和 IL-8）的产生，但会降低 BEAS-2B 细胞中抗病毒细胞因子干扰素-β（IFN-β）的产生，而 H3N2 单独暴露会增加 IL-6、IL-8 和 IFN-β 的产生。重要的是，先前暴露于 PM 增强了随后的 H3N2 感染性、病毒血凝素蛋白的表达以及 IL-6 和 IL-8 的上调，但降低了 H3N2 诱导的 IFN-β 产生。核因子-κB（NF-κB）的药理学抑制剂预处理可抑制 PM、H3N2 以及 PM 引发的 H3N2 感染诱导的促炎细胞因子产生。此外，Toll 样受体 4（TLR4）的抗体中和阻断了 PM 或 PM 引发的 H3N2 感染触发的细胞因子产生，但不能单独阻断 H3N2。总之，暴露于 PM 改变了 BEAS-2B 细胞中 H3N2 诱导的细胞因子产生和复制标志物，而这又受 NF-κB 和 TLR4 调节。
