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肥大细胞介导的过敏炎症与全氟化合物长度的相关性。

Correlation between mast cell-mediated allergic inflammation and length of perfluorinated compounds.

机构信息

a Department of Pharmacology, School of Medicine , Kyungpook National University , Daegu Republic of Korea.

出版信息

J Toxicol Environ Health A. 2018;81(9):302-313. doi: 10.1080/15287394.2018.1440188. Epub 2018 Feb 26.

DOI:10.1080/15287394.2018.1440188
PMID:29482476
Abstract

Perfluorinated compounds (PFC) have widely been used in numerous applications including clothing, food packaging, and nonstick coating. With the widespread use of PFC, concerns regarding potential adverse health effects in humans and wildlife have increased. In spite of the known PFC-mediated immunotoxiciy, correlation with PFC and allergic inflammation still requires elucidation. The aim of this study was to examine the effect of four types of PFC (perfluoroheptanoic acid [PFHpA], perfluorononanoic acid [PFNA], perfluorodecanoic acid [PFDA], and perfluoroundecanoic acid [PFUnA]) on mast cell-mediated allergic inflammation in the presence of high-affinity immunoglobulin (Ig) E receptor (FcεRI) cross-linking. Among PFC family, long-chain PFDA and PFUnA increased release of histamine and β-hexosaminidase by up-regulation of intracellular calcium levels in IgE-stimulated mast cells. In addition, PFDA and PFUnA enhanced gene expression of pro-inflammatory cytokines, such as tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, and IL-8 by activation of nuclear factor-κB in IgE-stimulated mast cells. In ovalbumin (OVA)-induced model of systemic anaphylaxis in the presence of hypothermia, PFNA, PFDA, and PFUnA exacerbated allergic symptoms accompanied by elevation in serum histamine, TNF-α, IgE, and IgG. Our data indicate that some PFC aggravated high-affinity IgE receptor (FcεRI)-mediated mast cell degranulation and allergic symptoms. Consequently, the results demonstrated that carbon-chain length of PFC may serve as a factor in allergic inflammation.

摘要

全氟化合物(PFC)广泛应用于服装、食品包装和不粘涂层等诸多领域。随着 PFC 的广泛使用,人们对其在人类和野生动物体内潜在不良健康影响的担忧日益增加。尽管已知 PFC 具有免疫毒性,但 PFC 与过敏炎症之间的相关性仍有待阐明。本研究旨在研究四种 PFC(全氟庚酸[PFHpA]、全氟壬酸[PFNA]、全氟癸酸[PFDA]和全氟十一烷酸[PFUnA])在高亲和力免疫球蛋白(Ig)E 受体(FcεRI)交联存在下对肥大细胞介导的过敏炎症的影响。在 PFC 家族中,长链 PFDA 和 PFUnA 通过上调 IgE 刺激的肥大细胞内钙离子水平,增加组胺和β-己糖胺酶的释放。此外,PFDA 和 PFUnA 通过激活 IgE 刺激的肥大细胞中的核因子-κB,增强促炎细胞因子如肿瘤坏死因子(TNF)-α、白细胞介素(IL)-1β、IL-6 和 IL-8 的基因表达。在 IgE 致敏的肥大细胞中,PFDA 和 PFUnA 通过激活核因子-κB,增强促炎细胞因子如肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)、白细胞介素-6(IL-6)和白细胞介素-8(IL-8)的基因表达。在低温存在下卵清蛋白(OVA)诱导的全身性过敏反应模型中,PFNA、PFDA 和 PFUnA 加重了过敏症状,同时伴有血清组胺、TNF-α、IgE 和 IgG 水平升高。我们的数据表明,一些 PFC 加重了高亲和力 IgE 受体(FcεRI)介导的肥大细胞脱颗粒和过敏症状。因此,结果表明 PFC 的碳链长度可能是过敏炎症的一个因素。

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