Circadian Rhythm Reprogramming During Lung Inflammation

Overview

Journal Nat Commun

Specialty Biology

Date 2014 Sep 12

PMID 25208554

Citations 114

Authors

Jeffrey A Haspel

Sukrutha Chettimada

Rahamthulla S Shaik

Jen-Hwa Chu

Benjamin A Raby

Manuela Cernadas

Vincent Carey

Vanessa Process

G Matthew Hunninghake

Emeka Ifedigbo

James A Lederer

Joshua Englert

Ashley Pelton

Anna Coronata

Laura E Fredenburgh

Augustine M K Choi

Affiliations

Soon will be listed here.

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.

Citing Articles

Metabolomic and transcriptomic analyses reveal differences in fatty acids in tobacco leaves across cultivars and developmental stages.

Chen Y, Wang S, He X, Gao J, Zhang X, Huang P BMC Plant Biol. 2025; 25(1):312.

PMID: 40069610 PMC: 11895271. DOI: 10.1186/s12870-025-06337-9.

Circadian Rhythms, Immune Regulation, and the Risk for Sepsis: Circadian Rhythms and Neonatal Care.

Sengupta S, Smith D, Koritala B Clin Perinatol. 2025; 52(1):185-197.

PMID: 39892952 PMC: 11788575. DOI: 10.1016/j.clp.2024.10.012.

Circadian metabolism regulates the macrophage inflammatory response.

Sun Y, Jiang W, Horng T Life Metab. 2025; 1(3):224-233.

PMID: 39872076 PMC: 11749265. DOI: 10.1093/lifemeta/loac037.

Physiological and Multi-Omics Integrative Analysis Provides New Insights into Tolerance to Waterlogging Stress in Sesame ( L.).

Zhang L, Wang S, Yang X, He L, Hu L, Tang R Int J Mol Sci. 2025; 26(1.

PMID: 39796205 PMC: 11720211. DOI: 10.3390/ijms26010351.

Integrated Transcriptomic, Proteomic, and Metabolomic Analyses Revealed Molecular Mechanism for Salt Resistance in Soybean ( L.) Seedlings.

Fu S, Wang L, Li C, Zhao Y, Zhang N, Yan L Int J Mol Sci. 2025; 25(24.

PMID: 39769326 PMC: 11678865. DOI: 10.3390/ijms252413559.

References

Martinon F, Petrilli V, Mayor A, Tardivel A, Tschopp J . Gout-associated uric acid crystals activate the NALP3 inflammasome. Nature. 2006; 440(7081):237-41. DOI: 10.1038/nature04516. View

ONeill J, Reddy A . Circadian clocks in human red blood cells. Nature. 2011; 469(7331):498-503. PMC: 3040566. DOI: 10.1038/nature09702. View

Zheng X, Sehgal A . AKT and TOR signaling set the pace of the circadian pacemaker. Curr Biol. 2010; 20(13):1203-8. PMC: 3165196. DOI: 10.1016/j.cub.2010.05.027. View

Green C, Takahashi J, Bass J . The meter of metabolism. Cell. 2008; 134(5):728-42. PMC: 3760165. DOI: 10.1016/j.cell.2008.08.022. View

Nakahata Y, Sahar S, Astarita G, Kaluzova M, Sassone-Corsi P . Circadian control of the NAD+ salvage pathway by CLOCK-SIRT1. Science. 2009; 324(5927):654-7. PMC: 6501775. DOI: 10.1126/science.1170803. View

Huang D, Sherman B, Lempicki R . Bioinformatics enrichment tools: paths toward the comprehensive functional analysis of large gene lists. Nucleic Acids Res. 2008; 37(1):1-13. PMC: 2615629. DOI: 10.1093/nar/gkn923. View

Dallmann R, Viola A, Tarokh L, Cajochen C, Brown S . The human circadian metabolome. Proc Natl Acad Sci U S A. 2012; 109(7):2625-9. PMC: 3289302. DOI: 10.1073/pnas.1114410109. View

Refinetti R, Lissen G, Halberg F . Procedures for numerical analysis of circadian rhythms. Biol Rhythm Res. 2013; 38(4):275-325. PMC: 3663600. DOI: 10.1080/09291010600903692. View

Gibbs J, Beesley S, Plumb J, Singh D, Farrow S, Ray D . Circadian timing in the lung; a specific role for bronchiolar epithelial cells. Endocrinology. 2008; 150(1):268-76. PMC: 4340583. DOI: 10.1210/en.2008-0638. View

10.

Zuber A, Centeno G, Pradervand S, Nikolaeva S, Maquelin L, Cardinaux L . Molecular clock is involved in predictive circadian adjustment of renal function. Proc Natl Acad Sci U S A. 2009; 106(38):16523-8. PMC: 2752602. DOI: 10.1073/pnas.0904890106. View

11.

de Lichtenberg U, Jensen L, Fausboll A, Jensen T, Bork P, Brunak S . Comparison of computational methods for the identification of cell cycle-regulated genes. Bioinformatics. 2004; 21(7):1164-71. DOI: 10.1093/bioinformatics/bti093. View

12.

Kondratov R, Kondratova A, Gorbacheva V, Vykhovanets O, Antoch M . Early aging and age-related pathologies in mice deficient in BMAL1, the core componentof the circadian clock. Genes Dev. 2006; 20(14):1868-73. PMC: 1522083. DOI: 10.1101/gad.1432206. View

13.

Kuipers M, Aslami H, Vlaar A, Juffermans N, Tuip-de Boer A, Hegeman M . Pre-treatment with allopurinol or uricase attenuates barrier dysfunction but not inflammation during murine ventilator-induced lung injury. PLoS One. 2012; 7(11):e50559. PMC: 3511544. DOI: 10.1371/journal.pone.0050559. View

14.

Ceriani M, Hogenesch J, Yanovsky M, Panda S, Straume M, Kay S . Genome-wide expression analysis in Drosophila reveals genes controlling circadian behavior. J Neurosci. 2002; 22(21):9305-19. PMC: 6758054. View

15.

Spengler C, Shea S . Endogenous circadian rhythm of pulmonary function in healthy humans. Am J Respir Crit Care Med. 2000; 162(3 Pt 1):1038-46. DOI: 10.1164/ajrccm.162.3.9911107. View

16.

Fregonezi G, Resqueti V, Cury J, Paulin E, Brunetto A . Diurnal variations in the parameters of pulmonary function and respiratory muscle strength in patients with COPD. J Bras Pneumol. 2012; 38(2):257-63. DOI: 10.1590/s1806-37132012000200016. View

17.

Bellet M, Deriu E, Liu J, Grimaldi B, Blaschitz C, Zeller M . Circadian clock regulates the host response to Salmonella. Proc Natl Acad Sci U S A. 2013; 110(24):9897-902. PMC: 3683799. DOI: 10.1073/pnas.1120636110. View

18.

Storch K, Lipan O, Leykin I, Viswanathan N, Davis F, Wong W . Extensive and divergent circadian gene expression in liver and heart. Nature. 2002; 417(6884):78-83. DOI: 10.1038/nature744. View

19.

Mavroudis P, Scheff J, Calvano S, Androulakis I . Systems biology of circadian-immune interactions. J Innate Immun. 2012; 5(2):153-62. PMC: 3717386. DOI: 10.1159/000342427. View

20.

Ermert L, Seeger W, DUNCKER H . Computer-assisted morphometry of the intracapillary leukocyte pool in the rabbit lung. Cell Tissue Res. 1993; 271(3):469-76. DOI: 10.1007/BF02913729. View