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首页> 外文期刊>Journal of Cellular Physiology >Expression variability and function of the RET gene in adult peripheral blood mononuclear cells
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Expression variability and function of the RET gene in adult peripheral blood mononuclear cells

机译：表达可变性和RET的函数基因在成人外周血单核细胞

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摘要

RET is a gene playing a key role during embryogenesis and in particular during the enteric nervous system development. High levels of RET gene expression are maintained in different human tissues also in adulthood, although their physiological role remains unclear. In particular, collected evidences of a RET contribution in the development and maintenance of the immune system prompted us to investigate its levels of surface expression on peripheral blood mononuclear cells (PBMCs) from adult healthy donors. Despite variability among samples, RET expression was conserved at similar levels in the different immune cell subsets, with higher correlations in similar lymphocyte populations (i.e. CD4+ and CD8+ T cells). Conversely, no correlation was found between the amount of RET receptor, the expression of its putative ligands and co-receptors and the genotypes at the RET locus. Moreover, we investigated the RET-associated inflammatory pathways in PBMCs from healthy donors both in resting conditions and upon glial cell derived neurotrophic factor (GDNF) and GPI-linked co-receptors alpha 1 (GFRα1) mediated RET activation. RET mRNA levels positively correlated with the transcript amount of interleukin-8 (IL-8), a cytokine produced by monocytes and macrophages, though we could not demonstrate its direct effect on RET expression by in vitro experiments on THP1 human monocytic cells. These results imply that RET expression might be influenced by either cis- and/or trans-factors, which together would account for its high variability within the general population, and suggest a putative functional role of the RET gene in modulating immune cell responses during inflammation and carcinogenesis.
机译：RET基因中发挥关键作用胚胎发生,特别是在肠神经系统的发展。维护的RET基因的表达不同的人体组织也在成年后,虽然他们的生理作用仍然存在不清楚。随著发展和贡献维护免疫系统的提示我们究其表面表达的水平外周血单核细胞(PBMCs)成人健康的捐赠者。样本,RET表达式是守恒的相似水平在不同的免疫细胞,子集更高的相关性淋巴细胞相似数量(例如CD4 +和CD8 + T细胞)。相反,之间不存在相关性RET受体,它的表达假定的配体和共受体RET基因型的轨迹。调查了RET-associated炎症通路PBMCs从健康的捐赠者休息条件和神经胶质细胞神经营养因子(GDNF)和gpi连接肾小球滤过率(GFR)共受体α1(α1)介导的后悔激活。interleukin-8的记录数量(引发)、单核细胞产生的细胞因子巨噬细胞,尽管我们不能展示自己直接影响RET体外表达实验THP1人类单核细胞的细胞。结果可能暗示RET表达式受顺式和/或trans-factors,在一起将占其高吗在一般人群中可变性,建议一个假定的RET的功能作用基因在调节免疫细胞的反应炎症和致癌作用。

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