Urban PM2.5 exacerbates allergic inflammation in the murine lung via a TLR2/TLR4/MyD88-signaling pathway.
Urban PM2.5 exacerbates allergic inflammation in the murine lung via a TLR2/TLR4/MyD88-signaling pathway.
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DOI：
10.1038/s41598-017-11471-y
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发表时间：
2017-09-08
影响因子：
4.6
通讯作者：
Shibamoto T
中科院分区：
文献类型：
--
作者：
He M;Ichinose T;Yoshida Y;Arashidani K;Yoshida S;Takano H;Sun G;Shibamoto T
然而，PM2.5的作用机制还没有得到很好的解释，PM2.5被认为可以加重哮喘。本研究探讨Toll样受体2、TLR4和MyD88在城市PM2.5致变应原致肺嗜酸粒细胞增多症中的作用。TLR2-、TLR4-、MyD88基因缺陷小鼠和WT BALB/c小鼠被PM2.5+/−卵清蛋白(OVA)气管内激发，间隔2周，共4次。PM2.5可增加WT小鼠支气管肺泡灌洗液中中性粒细胞数和肺泡灌洗液中的KC，并引起轻度的细支气管炎。然而，这些变化在基因缺陷小鼠中得到了减弱，但并未完全被抑制，特别是在MyD88−/−小鼠中。在WT小鼠中，PM2.5OVA加重了 + 相关的肺嗜酸性粒细胞增多症。这种加重包括IL-5、IL-13、Eoaxin和MCP-3的增加；嗜酸性粒细胞在呼吸道粘膜下层的渗透；气道上皮内杯状细胞的增殖；以及血清中抗原特异性IgE和IgG1的产生。这些作用在TLR2−/−小鼠中比在TLR4−/−小鼠中更强。在MyD88−/−小鼠中，这种促炎介质的诱导能力相当弱，肺部病理可以忽略不计。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内的过敏性炎症。PM2.5结合的微量微生物元素，如脂多糖，可能是加剧小鼠肺嗜酸性粒细胞增多症的有力候选者。
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.
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白介素5缺乏消除小鼠哮喘模型中的嗜酸性粒细胞，气道高反应性和肺损伤。
影响因子：
15.3
作者：
Foster, PS;Hogan, SP;Ramsay, AJ;Matthaei, KI;Young, IG
通讯作者：
Young, IG
影响因子：
4.8
作者：
Schwandner, R;Dziarski, R;Kirschning, CJ
通讯作者：
Kirschning, CJ
影响因子：
2.1
作者：
He, Miao;Ichinose, Takamichi;Shibamoto, Takayuki
通讯作者：
Shibamoto, Takayuki
影响因子：
5.4
作者：
Gehring, Ulrike;Beelen, Rob;Brunekreef, Bert
通讯作者：
Brunekreef, Bert
DOI：
10.1016/s0021-9673(01)87923-1
发表时间：
1983-01-01
期刊：
JOURNAL OF CHROMATOGRAPHY
影响因子：
--
作者：
KODAMA, Y;ARASHIDANI, K;YOSHIKAWA, M
通讯作者：
YOSHIKAWA, M