Corticotropin-releasing hormone and extracellular mitochondria augment IgE-stimulated human mast-cell vascular endothelial growth factor release, which is inhibited by luteolin.

Corticotropin-releasing hormone and extracellular mitochondria augment IgE-stimulated human mast-cell vascular endothelial growth factor release, which is inhibited by luteolin.
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DOI:
10.1186/1742-2094-9-85
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发表时间:
2012-05-04
影响因子:
9.3
通讯作者:
Theoharides TC
Theoharides TC
中科院分区:
医学1区
文献类型:
--
作者:
Asadi S;Theoharides TC

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自闭症谱系障碍(ASD)是一种神经发育障碍,其特征是不同程度的社交能力障碍、学习缺陷和刻板行为。许多ASD患者有“过敏样”症状,并对压力做出反应。我们以前已经表明,肽神经降压素(NT)在自闭症幼儿的血清中增加,可以刺激线粒体(mt)DNA的细胞外分泌,这也增加了这些儿童的血清中。通过促肾上腺皮质激素释放激素(CRH)、线粒体DNA、IgE/抗IgE刺激人肥大细胞24小时以通过ELISA测量血管内皮生长因子(VEGF)释放,或刺激人肥大细胞6小时或定量PCR。CRH增强IgE/抗IgE诱导的人肥大细胞VEGF的释放,并诱导肥大细胞上IgE受体(FcεRI)的表达。此外,超声处理的线粒体也增加了VEGF的释放,这种作用被天然黄酮木樨草素阻断。这些结果表明,压力和感染模拟细胞外线粒体成分增加过敏性炎症,可能参与ASD的早期发病机制。此外,毛地黄黄酮抑制这些过程,可能有助于治疗ASD。
Autism spectrum disorders (ASDs) are neurodevelopmental disorders characterized by varying degrees of dysfunctional social abilities, learning deficits, and stereotypic behaviors. Many patients with ASDs have ‘allergy-like’ symptoms and respond disproportionally to stress. We have previously shown that the peptide neurotensin (NT) is increased in the serum of young children with autism and that can stimulate extracellular secretion of mitochondrial (mt)DNA which was also increased in the serum of these children. Human mast cells were stimulated by corticotropin-releasing hormone (CRH), mitochondrial DNA, IgE/anti-IgE, either for 24 hours to measure vascular endothelial growth factor (VEGF) release by ELISA or for 6 hours or quantitative PCR. CRH augmented IgE/anti-IgE-induced human mast-cell release of VEGF and it also induced the expression of IgE receptor (FcεRI) on mast cells. Moreover, sonicated mitochondria also augmented VEGF release, and this effect was blocked by the natural flavone luteolin. These results indicate that stress and infection-mimicking extracellular mitochondrial components augment allergic inflammation that may be involved in the early pathogenesis of ASDs. Moreover, luteolin inhibits these processes and may be helpful in the treatment of ASDs.
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