Transplacental passage of interleukins 4 and 13?

Transplacental passage of interleukins 4 and 13?
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白细胞介素 4 和 13 经胎盘通过?

DOI:
10.1371/journal.pone.0004660
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发表时间:
2009
期刊:
影响因子:
3.7
通讯作者:
Kobzik, Lester
Kobzik, Lester
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Lim, Robert H.;Kobzik, Lester

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产前事件影响成人疾病发展的机制还不完全清楚。基于哮喘风险的母体传播的小鼠模型中的发现,我们试图测试促哮喘细胞因子白细胞介素-4和-13的作用。为了评估功能性细胞因子的经胎盘通过,我们测定了STAT-6的磷酸化,STAT-6是通过需要IL-4受体α亚基的异二聚体受体复合物的IL-4和IL-13信号传导的标志物。将IL-4受体α −/−雌性与野生型雄性交配,并向妊娠雌性注射超生理剂量的IL-4或13。注射后1小时,收获受体杂合子胚胎,并通过Western印迹分析组织核蛋白提取物中STAT-6的磷酸化。虽然直接注射胚胎产生了强阳性对照,但在母体注射IL-4或IL-13后未观察到磷酸化,表明两者均未以可检测的量穿过胎盘。这些数据证明了一种有用的方法来测定功能性母体分子的经胎盘通过,并表明IL-4和IL-13以外的分子可能介导哮喘风险的母体传播中的经胎盘作用。
The mechanisms by which prenatal events affect development of adult disease are incompletely characterized. Based on findings in a murine model of maternal transmission of asthma risk, we sought to test the role of the pro-asthmatic cytokines interleukin IL-4 and -13. To assess transplacental passage of functional cytokines, we assayed phosphorylation of STAT-6, a marker of IL-4 and -13 signaling via heterodimeric receptor complexes which require an IL-4 receptor alpha subunit. IL-4 receptor alpha−/− females were mated to wild-type males, and pregnant females were injected with supraphysiologic doses of IL-4 or 13. One hour after injection, the receptor heterozygotic embryos were harvested and tissue nuclear proteins extracts assayed for phosphorylation of STAT-6 by Western blot. While direct injection of embryos produced a robust positive control, no phosphorylation was seen after maternal injection with either IL-4 or -13, indicating that neither crossed the placenta in detectable amounts. The data demonstrate a useful approach to assay for transplacental passage of functional maternal molecules, and indicate that molecules other than IL-4 and IL-13 may mediate transplacental effects in maternal transmission of asthma risk.
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