School of Respiratory Therapy, College of Medicine, Taipei Medical University, Taipei, Taiwan; Division of Pulmonary Medicine, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan.
School of Public Health, College of Public Health, Taipei Medical University, Taipei, Taiwan; Department of Public Health, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
Chem Biol Interact. 2019 Sep 25;311:108762. doi: 10.1016/j.cbi.2019.108762. Epub 2019 Jul 23.
Neurotoxicity caused by particulate matter (PM) has been highlighted as being a potential risk factor for neurodegenerative diseases. However, the effects of brain inflammation in response to traffic-related PM remain unclear. The objective of this study was to investigate the effects of traffic-related PM on microglial responses. We determined the cytotoxicity, oxidative stress, lipid peroxidation, inflammation, activation, autophagy, and apoptosis due to exposure to carbon black (CB) and diesel exhaust particles (DEPs) in Bv2 microglial cells. Additionally, cells were pretreated with corticosteroid to determine alterations in microglial activation and inflammation. For in vivo confirmation, Sprague Dawley (SD) rats were whole-body exposed to traffic-related PM (PM with an aerodynamic diameter of <1 μm) for 3 and 6 months. We observed that a decrease in cell viability and increases in dichlorodihydrofluorescein (DCFH), lactate dehydrogenase (LDH), and thiobarbituric acid-reactive substances (TBARSs) occurred due to CB and DEP. Production of interleukin (IL)-6 and soluble tumor necrosis factor (TNF)-α was significantly stimulated by CB and DEP, whereas production of cellular TNF-α was significantly stimulated by CB. Iba1 and prostaglandin E2 (PGE2) significantly increased due to CB and DEP. Consistently, we observed significant increases in Iba1 in the hippocampus of rats after 3 and 6 months of exposure to traffic-related PM. We found that the light chain 3II (LC3II)/LC3I ratio and caspase-3 activity increased due to CB and DEP exposure. Subsequently, LDH, TBARS, LC3II/I, and caspase-3 activities did not clearly respond to corticosteroid pretreatment followed by DEP exposure in BV2 cells. Results of the present study suggested that traffic-related PM induced cytotoxicity, lipid peroxidation, microglial activation, and inflammation as well as autophagy and caspase-3 regulation in microglia. We demonstrated that microglial activation and inflammation may play important roles in the response of the brain to traffic-related PM.
颗粒物（PM）引起的神经毒性已被强调为神经退行性疾病的潜在风险因素。然而，交通相关 PM 引起的大脑炎症的影响尚不清楚。本研究旨在研究交通相关 PM 对小胶质细胞反应的影响。我们测定了在 Bv2 小胶质细胞中暴露于炭黑（CB）和柴油机排气颗粒（DEP）时的细胞毒性、氧化应激、脂质过氧化、炎症、激活、自噬和细胞凋亡。此外，细胞用皮质类固醇预处理，以确定小胶质细胞激活和炎症的变化。为了进行体内验证，Sprague Dawley（SD）大鼠全身暴露于交通相关 PM（空气动力学直径<1μm 的 PM）3 个月和 6 个月。我们观察到，由于 CB 和 DEP，细胞活力下降，二氯二氢荧光素（DCFH）、乳酸脱氢酶（LDH）和硫代巴比妥酸反应物质（TBARS）增加。CB 和 DEP 显著刺激白细胞介素（IL）-6 和可溶性肿瘤坏死因子（TNF）-α 的产生，而 CB 显著刺激细胞 TNF-α的产生。由于 CB 和 DEP，Iba1 和前列腺素 E2（PGE2）显著增加。一致地，我们观察到暴露于交通相关 PM 3 个月和 6 个月后大鼠海马中 Iba1 显著增加。我们发现由于 CB 和 DEP 暴露，LC3II/LC3I 比值和半胱天冬酶-3 活性增加。随后，在 BV2 细胞中用皮质类固醇预处理后再暴露于 DEP 时，LDH、TBARS、LC3II/I 和半胱天冬酶-3 活性没有明显反应。本研究结果表明，交通相关 PM 诱导小胶质细胞的细胞毒性、脂质过氧化、小胶质细胞激活和炎症以及自噬和半胱天冬酶-3 调节。我们证明，小胶质细胞激活和炎症可能在大脑对交通相关 PM 的反应中发挥重要作用。
