1. Circadian rhythm reprogramming during lung inflammation.
- Author
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Haspel JA, Chettimada S, Shaik RS, Chu JH, Raby BA, Cernadas M, Carey V, Process V, Hunninghake GM, Ifedigbo E, Lederer JA, Englert J, Pelton A, Coronata A, Fredenburgh LE, and Choi AM
- Subjects
- Animals, CLOCK Proteins immunology, CLOCK Proteins metabolism, Circadian Rhythm immunology, Circadian Rhythm Signaling Peptides and Proteins genetics, Circadian Rhythm Signaling Peptides and Proteins immunology, Circadian Rhythm Signaling Peptides and Proteins metabolism, Endotoxins toxicity, Gene Expression Regulation, Granulocytes immunology, Leukocyte Count, Lung immunology, Lymphocytes immunology, Mice, Pneumonia chemically induced, Pneumonia metabolism, CLOCK Proteins genetics, Circadian Rhythm genetics, Lung metabolism, Pneumonia genetics, RNA, Messenger metabolism
- Abstract
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.
- Published
- 2014
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