A circadian clock in murine bone marrow-derived mast cells modulates IgE-dependent activation in vitro
A circadian clock in murine bone marrow-derived mast cells modulates IgE-dependent activation in vitro
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DOI：
10.1016/j.bbi.2010.09.007
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发表时间：
2011-01-01
影响因子：
15.1
通讯作者：
Brown, Jared M.
中科院分区：
文献类型：
--
作者：
Wang, Xiaojia;Reece, Shaun P.;Brown, Jared M.
昼夜节律在大多数生物体中都有表达，免疫系统中的许多功能和参数都与一天中的时间有关。然而，免疫细胞中的局部生物钟是否直接控制生理结果在很大程度上是未知的。我们假设，在小鼠骨髓来源的肥大细胞（BMMCs）的昼夜节律钟调节IgE依赖的激活在体外。用富含血清的培养基（50%马血清）使从C57 BL/6小鼠骨髓生长的成熟BMMC同步化。在同步化后以4小时间隔从BMMC收获总RNA长达72小时，并通过定量PCR测量昼夜节律基因（mPer 1、mPer 2、Bmal 1、Rev-erb α和Dbp）的表达。血清休克使BMMC中的昼夜节律基因（mPer 2、Bmal 1、Rev-erb α和Dbp）的表达同步。通过高亲和力IgE受体（Fc β RI）在不同时间间隔刺激的同步BMMC显示IL-13和IL-6 mRNA表达的昼夜节律。fcer 1a基因和Fc ε RI α蛋白的表达在血清休克后呈现昼夜节律模式，平均周期分别为18.9和28.6 h。这些结果表明，同步化的BMMC提供了研究与过敏性疾病相关的昼夜节律机制的体外模型，并且IgE依赖性激活后细胞因子产生的昼夜节律振荡至少部分是由于Fc β RI α的昼夜节律振荡。(C)2010年爱思唯尔公司All rights reserved.
Circadian rhythm is expressed in most organisms, and many functions and parameters in the immune system are associated with time-of-day. However, it is largely unknown if local circadian clocks in immune cells directly control physiological outcomes. We hypothesized that a circadian clock in murine bone marrow derived mast cells (BMMCs) modulates IgE-dependent activation in vitro. Mature BMMCs, grown from bone marrow of C57BL/6 mice, were synchronized with serum rich media (50% horse serum). Total RNA was harvested from BMMCs at 4 h intervals for up to 72 h following synchronization and expression of circadian genes (mPer1, mPer2, Bmal1, Rev-erb alpha, and Dbp) was measured by quantitative PCR. Serum shock synchronized expression of circadian genes (mPer2, Bmal1, Rev-erb alpha, and Dbp) in BMMCs. Synchronized BMMCs stimulated via the high affinity IgE receptor (Fc epsilon RI) at different time intervals display circadian rhythms in IL-13 and IL-6 mRNA expression. The expression of fcer1a gene and Fc epsilon RI alpha protein displayed a circadian pattern following serum shock, with mean periods of 18.9 and 28.6 h, respectively. These results demonstrate that synchronized BMMCs provide an in vitro model to study circadian mechanism(s) associated with allergic disease and that circadian oscillation of cytokine production following IgE-dependent activation is at least in part due to circadian oscillation of Fc epsilon RI alpha. (C) 2010 Elsevier Inc. All rights reserved.