Regulation of cytokine production in human alveolar macrophages and airway epithelial cells in response to ambient air pollution particles: further mechanistic studies.
Regulation of cytokine production in human alveolar macrophages and airway epithelial cells in response to ambient air pollution particles: further mechanistic studies.
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DOI：
10.1016/j.taap.2005.01.023
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发表时间：
2005-09-01
影响因子：
3.8
通讯作者：
Madden, Michael
中科院分区：
文献类型：
--
作者：
Becker, Susanne;Mundandhara, Sailaja;Madden, Michael
为了更好地了解环境空气颗粒物（PM）如何影响肺部健康，两种主要的气道细胞类型可能与吸入颗粒相互作用，肺泡巨噬细胞（AM）和气道上皮细胞在体外暴露于颗粒，并跟踪炎症和氧化应激的终点。将Chapel Hill PM10分离成细颗粒和粗颗粒表明AM中的主要促炎反应（TNF, IL-6, COX-2）是由粗颗粒PM中存在的物质驱动的，PM10中含有90-95%的刺激物质。这些颗粒不影响氧合酶-1 （HO-1）的表达，氧合酶-1是氧化应激的敏感标志物。原代培养的正常人支气管上皮细胞（NHBE）对粗粒颗粒的IL-8和COX-2水平也高于细粒或超细粒PM诱导的水平。所有大小PM均诱导NHBE氧化应激，而细粒PM诱导的HO-1表达水平最高。AM中粗颗粒和细颗粒细胞因子的产生均被toll样受体4 （TLR4）拮抗剂E5531阻断，该拮抗剂参与LPS和革兰氏阴性菌的识别。发现NHBE通过TLR2识别粗PM和细PM， TLR2是一种优先识别革兰氏阳性细菌的受体。与环境PM相比，柴油PM在AM和NHBE中仅诱导最小的细胞因子反应。相反，柴油抑制lps诱导的AM中TNF和IL-8的释放。粗颗粒物和细颗粒物均对lps诱导的TNF释放有抑制作用，而二氧化硅、火山灰和炭黑则无抑制作用。柴油颗粒不影响细胞因子mRNA的诱导和蛋白质的积累，但干扰细胞因子的释放。另一方面，环境粗粒和细粒PM均抑制mRNA诱导和蛋白质产生。粗粒PM和细粒PM均可降低巨噬细胞中TLR4的表达。颗粒诱导的TLR4减少和对LPS的低反应性可能与低水平LPS诱导的LPS耐受有关。
In order to better understand how ambient air particulate matter (PM) affect lung health, the two main airway cell types likely to interact with inhaled particles, alveolar macrophages (AM) and airway epithelial cells have been exposed to particles in vitro and followed for endpoints of inflammation, and oxidant stress. Separation of Chapel Hill PM 10 into fine and coarse size particles revealed that the main proinflammatory response (TNF, IL-6, COX-2) in AM was driven by material present in the coarse PM, containing 90-95% of the stimulatory material in PM10. The particles did not affect expression of hemoxygenase-1 (HO-1), a sensitive marker of oxidant stress. Primary cultures of normal human bronchial epithelial cells (NHBE) also responded to the coarse fraction with higher levels of IL-8 and COX-2, than induced by fine or ultrafine PM. All size PM induced oxidant stress in NHBE, while fine PM induced the highest levels of HO-1 expression. The production of cytokines in AM by both coarse and fine particles was blocked by the toll like receptor 4 (TLR4) antagonist E5531 involved in the recognition of LPS and Gram negative bacteria. The NHBE were found to recognize coarse and fine PM through TLR2, a receptor with preference for recognition of Gram positive bacteria. Compared to ambient PM, diesel PM induced only a minimal cytokine response in both AM and NHBE. Instead, diesel suppressed LPS-induced TNF and IL-8 release in AM. Both coarse and fine ambient air PM were also found to inhibit LPS-induced TNF release while silica, volcanic ash or carbon black had no inhibitory effect. Diesel particles did not affect cytokine mRNA induction nor protein accumulation but interfered with the release of cytokine from the cells. Ambient coarse and fine PM, on the other hand, inhibited both mRNA induction and protein production. Exposure to coarse and fine PM decreased the expression of TLR4 in the macrophages. Particle-induced decrease in TLR4 and hyporesponsiveness to LPS may be related to LPS tolerance induced by low levels of LPS.