Cortisol-treated zebrafish embryos develop into pro-inflammatory adults with aberrant immune gene regulation
Cortisol-treated zebrafish embryos develop into pro-inflammatory adults with aberrant immune gene regulation
复制标题
DOI：
10.1242/bio.020065
复制
发表时间：
2016-08-15
期刊：
影响因子：
2.4
通讯作者：
Coffman, James A.
中科院分区：
文献类型：
--
作者：
Hartig, Ellen I.;Zhu, Shusen;Coffman, James A.
慢性早期应激增加了成年人对与慢性炎症有关的许多健康问题的易感性。这可能发生的一种方式是通过糖皮质激素诱导的发育规划。为了深入了解这种编程，我们用皮质醇处理斑马鱼胚胎，并检查了对幼虫和成鱼的影响。经处理的幼虫全身皮质醇和糖皮质激素信号增强，与防御反应和免疫系统过程相关的基因上调。在成年期，在没有外源皮质醇的情况下，处理的鱼保持了较高的基础皮质醇水平，并结构性地错误表达了涉及防御反应及其调节的基因。来自皮质醇处理的胚胎的成体表现出尾鳍再生缺陷，促炎基因的基础表达增加，以及在损伤或免疫挑战后未能适当地调节这些基因。这些结果支持这样的假设，即生命早期长期升高的糖皮质激素信号指导着促炎成人表型的发育，代价是免疫调节和躯体再生能力。
Chronic early-life stress increases adult susceptibility to numerous health problems linked to chronic inflammation. One way that this may occur is via glucocorticoid-induced developmental programming. To gain insight into such programming we treated zebrafish embryos with cortisol and examined the effects on both larvae and adults. Treated larvae had elevated whole-body cortisol and glucocorticoid signaling, and upregulated genes associated with defense response and immune system processes. In adulthood the treated fish maintained elevated basal cortisol levels in the absence of exogenous cortisol, and constitutively mis-expressed genes involved in defense response and its regulation. Adults derived from cortisol-treated embryos displayed defective tailfin regeneration, heightened basal expression of pro-inflammatory genes, and failure to appropriately regulate those genes following injury or immunological challenge. These results support the hypothesis that chronicallyelevated glucocorticoid signaling early in life directs development of a pro-inflammatory adult phenotype, at the expense of immunoregulation and somatic regenerative capacity.