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子宫内营养不良会改变Wistar大鼠的TH1/TH2细胞因子平衡并减轻肺部过敏性炎症。

Intrauterine undernourishment alters TH1/TH2 cytokine balance and attenuates lung allergic inflammation in wistar rats.

作者信息

Landgraf Maristella A, Landgraf Richardt G, Silva Reinaldo C, Semedo Patrícia, Câmara Niels O S, Fortes Zuleica B

机构信息

Laboratorio de Imunologia dos Transplantes, Departamento de Imunologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, Brazil.

出版信息

Cell Physiol Biochem. 2012;30(3):552-62. doi: 10.1159/000341437. Epub 2012 Jul 23.

Abstract

IL-4 produced by Th2 cells can block cytokine production by Th1 cells, and Th1 IFN-γ is known to counterregulate Th2 immune response, inhibiting allergic eosinophilia. As intrauterine undernutrition can attenuate lung inflammation, we investigated the influence of intrauterine undernourishment on the Th1/Th2 cytokine balance and allergic lung inflammation. Intrauterine undernourished offspring were obtained from dams fed 50% of the nourished diet of their counterparts and were immunized at 9 weeks of age. We evaluated the cell counts and cytokine protein expression in the bronchoalveolar lavage, mucus production and collagen deposition, and cytokine gene expression and transcription factors in lung tissue 21 days after ovalbumin immunization. Intrauterine undernourishment significantly reduced inflammatory cell airway infiltration, mucus secretion and collagen deposition, in rats immunized and challenged. Intrauterine undernourished rats also exhibited an altered cytokine expression profile, including higher TNF-α and IL-1β expression and lower IL-6 expression than well-nourished rats following immunization and challenge. Furthermore, the intrauterine undernourished group showed reduced ratios of the IL-4/IFN-γ and the transcription factors GATA-3/T-Bet after immunization and challenge. We suggest that the attenuated allergic lung inflammation observed in intrauterine undernourished rats is related to an altered Th1/Th2 cytokine balance resulting from a reduced GATA-3/T-bet ratio.

摘要

Th2细胞产生的白细胞介素-4可抑制Th1细胞产生细胞因子,而Th1细胞产生的干扰素-γ则可对Th2免疫反应进行反向调节,抑制过敏性嗜酸性粒细胞增多。由于子宫内营养不良可减轻肺部炎症,我们研究了子宫内营养不足对Th1/Th2细胞因子平衡及过敏性肺部炎症的影响。子宫内营养不足的后代由喂食量为对照组营养饮食50%的母鼠所生,并在9周龄时进行免疫。我们在卵清蛋白免疫21天后评估了支气管肺泡灌洗中的细胞计数和细胞因子蛋白表达、黏液分泌和胶原沉积,以及肺组织中的细胞因子基因表达和转录因子。在免疫和激发后的大鼠中,子宫内营养不足显著减少了炎性细胞在气道的浸润、黏液分泌和胶原沉积。子宫内营养不足的大鼠在免疫和激发后还表现出细胞因子表达谱的改变,包括与营养良好的大鼠相比,肿瘤坏死因子-α和白细胞介素-1β表达更高,白细胞介素-6表达更低。此外,子宫内营养不足组在免疫和激发后白细胞介素-4/干扰素-γ的比值以及转录因子GATA-3/T-Bet降低。我们认为,在子宫内营养不足的大鼠中观察到的过敏性肺部炎症减轻与GATA-3/T-bet比值降低导致的Th1/Th2细胞因子平衡改变有关。

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