Department of Environmental Health, School of Public Health, China Medical University, Shenyang, 110122, China.
Department of Health Sciences, Oita University of Nursing and Health Sciences, Oita, 870-1201, Japan.
Sci Rep. 2017 Sep 8;7(1):11027. doi: 10.1038/s41598-017-11471-y.
Nevertheless its mechanism has not been well explained yet, PM2.5 is recognized to exacerbate asthma. In the present study, the roles of toll-like receptor (TLR) 2, TLR4 and MyD88, in exacerbation of allergen-induced lung eosinophilia caused by urban PM2.5 was investigated. TLR2-, TLR4-, MyD88-deficient and WT BALB/c mice were intratracheally challenged with PM2.5 +/- ovalbumin (OVA) four times at 2-week intervals. PM2.5 increased neutrophil numbers and KC in bronchoalveolar lavage fluid and caused slight peribronchiolar inflammation in WT mice. However, these changes were attenuated, but not completely suppressed in gene-deficient mice, especially in MyD88 mice. In WT mice, PM2.5 + OVA exacerbated OVA-related lung eosinophilia. This exacerbation includes increase of IL-5, IL-13, eotaxin and MCP-3; infiltration of eosinophils into the airway submucosa; proliferation of goblet cells in the airway epithelium; and the production of antigen-specific IgE and IgG1 in serum. All these effects were stronger in TLR2 mice than in TLR4 mice. In MyD88 mice, this pro-inflammatory mediator-inducing ability was considerably weak and lung pathology was negligible. These results suggest that urban PM2.5 may exacerbate allergic inflammation in the murine lung via a TLR2/TLR4/MyD88-signaling pathway. PM2.5-bound trace microbial elements, such as lipopolysaccharide may be a strong candidate for exacerbation of murine lung eosinophilia.
然而，其机制尚未得到很好的解释，PM2.5 被认为会加重哮喘。在本研究中，研究了 Toll 样受体（TLR）2、TLR4 和 MyD88 在城市 PM2.5 加重变应原诱导的肺嗜酸性粒细胞增多中的作用。TLR2-、TLR4-、MyD88 缺陷和 WT BALB/c 小鼠每隔 2 周通过气管内挑战 PM2.5 +/-卵清蛋白（OVA）四次。PM2.5 增加了支气管肺泡灌洗液中的中性粒细胞数量和 KC，并在 WT 小鼠中引起轻微的细支气管周围炎症。然而，这些变化在基因缺陷小鼠中减弱，但并未完全抑制，尤其是在 MyD88 小鼠中。在 WT 小鼠中，PM2.5+OVA 加重了 OVA 相关的肺嗜酸性粒细胞增多。这种加重包括 IL-5、IL-13、嗜酸性粒细胞趋化因子和 MCP-3 的增加；气道粘膜下嗜酸性粒细胞浸润；气道上皮中杯状细胞的增殖；以及血清中抗原特异性 IgE 和 IgG1 的产生。所有这些影响在 TLR2 小鼠中比在 TLR4 小鼠中更强。在 MyD88 小鼠中，这种促炎介质诱导能力相当弱，肺病理学可忽略不计。这些结果表明，城市 PM2.5 可能通过 TLR2/TLR4/MyD88 信号通路加重小鼠肺部的过敏性炎症。PM2.5 结合的痕量微生物成分，如脂多糖，可能是加重小鼠肺嗜酸性粒细胞增多的强候选物。
