Dasari Pallave, Sharkey David J, Noordin Effarina, Glynn Danielle J, Hodson Leigh J, Chin Peck Y, Evdokiou Andreas, Robertson Sarah A, Ingman Wendy V
Discipline of Surgery, School of Medicine, The Queen Elizabeth Hospital, University of Adelaide, Woodville, Australia; School of Paediatrics and Reproductive Health, University of Adelaide, Australia; Research Centre for Reproductive Health, The Robinson Institute, University of Adelaide, Australia.
School of Paediatrics and Reproductive Health, University of Adelaide, Australia; Research Centre for Reproductive Health, The Robinson Institute, University of Adelaide, Australia.
J Reprod Immunol. 2014 Dec;106:58-66. doi: 10.1016/j.jri.2014.07.002. Epub 2014 Jul 30.
The mammary gland is a unique organ that undergoes hormone-driven developmental changes over the course of the ovarian cycle during adult life. Macrophages play a role in regulating cellular turnover in the mammary gland and may affect cancer susceptibility. However, the immune microenvironment that regulates macrophage function has not been described. Hormonal regulation of the cytokine microenvironment across the ovarian cycle was explored using microbead multiplex assay for 15 cytokines in mammary glands from C57Bl/6 mice at different stages of the oestrous cycle, and in ovariectomised mice administered oestradiol and progesterone. The cytokines that were found to fluctuate over the course of the oestrous cycle were colony-stimulating factor (CSF)1, CSF2, interferon gamma (IFNG) and tumour necrosis factor alpha (TNFA), all of which were significantly elevated at oestrus compared with other phases. The concentration of serum progesterone during the oestrus phase negatively correlated with the abundance of cytokines CSF3, IL12p40, IFNG and leukaemia inhibitory factor (LIF). In ovariectomised mice, exogenous oestradiol administration increased mammary gland CSF1, CSF2, IFNG and LIF, compared with ovariectomised control mice. Progesterone administration together with oestradiol resulted in reduced CSF1, CSF3 and IFNG compared with oestradiol administration alone. This study suggests that the cytokine microenvironment in the mammary gland at the oestrus phase of the ovarian cycle is relatively pro-inflammatory compared with other stages of the cycle, and that the oestradiol-induced cytokine microenvironment is significantly attenuated by progesterone. A continuously fluctuating cytokine microenvironment in the mammary gland presumably regulates the phenotypes of resident leukocytes and may affect mammary gland cancer susceptibility.
乳腺是一个独特的器官，在成年期的卵巢周期中会经历激素驱动的发育变化。巨噬细胞在调节乳腺细胞更新中发挥作用，并可能影响癌症易感性。然而，调节巨噬细胞功能的免疫微环境尚未得到描述。利用微珠多重分析法，对处于发情周期不同阶段的C57Bl/6小鼠乳腺以及接受雌二醇和孕酮处理的去卵巢小鼠乳腺中的15种细胞因子进行了检测，以探究卵巢周期中细胞因子微环境的激素调节。发现在发情周期中波动的细胞因子有集落刺激因子（CSF）1、CSF2、干扰素γ（IFNG）和肿瘤坏死因子α（TNFA），与其他阶段相比，这些细胞因子在发情期均显著升高。发情期血清孕酮浓度与细胞因子CSF3、IL12p40、IFNG和白血病抑制因子（LIF）的丰度呈负相关。在去卵巢小鼠中，与去卵巢对照小鼠相比，外源性给予雌二醇可增加乳腺中CSF1、CSF2、IFNG和LIF的水平。与单独给予雌二醇相比，同时给予孕酮和雌二醇会导致CSF1、CSF3和IFNG水平降低。这项研究表明，与卵巢周期的其他阶段相比，发情期乳腺中的细胞因子微环境相对具有促炎作用，并且孕酮可显著减弱雌二醇诱导的细胞因子微环境。乳腺中持续波动的细胞因子微环境可能调节驻留白细胞的表型，并可能影响乳腺癌易感性。
