Haspel Jeffrey A, Chettimada Sukrutha, Shaik Rahamthulla S, Chu Jen-Hwa, Raby Benjamin A, Cernadas Manuela, Carey Vincent, Process Vanessa, Hunninghake G Matthew, Ifedigbo Emeka, Lederer James A, Englert Joshua, Pelton Ashley, Coronata Anna, Fredenburgh Laura E, Choi Augustine M K
Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, 75 Francis Street, Boston, Massachusetts 02215, USA.
Channing Division of Network Medicine, Brigham and Women's Hospital, 181 Longwood Avenue, Boston, Massachusetts 02215, USA.
Nat Commun. 2014 Sep 11;5:4753. doi: 10.1038/ncomms5753.
Circadian rhythms are known to regulate immune responses in healthy animals, but it is unclear whether they persist during acute illnesses where clock gene expression is disrupted by systemic inflammation. Here we use a genome-wide approach to investigate circadian gene and metabolite expression in the lungs of endotoxemic mice and find that novel cellular and molecular circadian rhythms are elicited in this setting. The endotoxin-specific circadian programme exhibits unique features, including a divergent group of rhythmic genes and metabolites compared with the basal state and a distinct periodicity and phase distribution. At the cellular level, endotoxin treatment also alters circadian rhythms of leukocyte counts within the lung in a bmal1-dependent manner, such that granulocytes rather than lymphocytes become the dominant oscillating cell type. Our results show that inflammation produces a complex re-organization of cellular and molecular circadian rhythms that are relevant to early events in lung injury.
已知昼夜节律可调节健康动物的免疫反应，但尚不清楚在急性疾病期间，当系统炎症破坏生物钟基因表达时，昼夜节律是否依然存在。在此，我们采用全基因组方法研究内毒素血症小鼠肺组织中的昼夜节律基因和代谢物表达，发现在这种情况下会引发新的细胞和分子昼夜节律。内毒素特异性昼夜节律程序具有独特特征，包括与基础状态相比，一组不同的节律基因和代谢物，以及独特的周期和相位分布。在细胞水平上，内毒素处理还以依赖于bmal1的方式改变肺内白细胞计数的昼夜节律，使得粒细胞而非淋巴细胞成为主要的振荡细胞类型。我们的结果表明，炎症会导致细胞和分子昼夜节律发生复杂的重新组织，这与肺损伤的早期事件相关。
