title: Circadian rhythm reprogramming during lung inflammation.
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.
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, 75 Francis Street, Boston, Massachusetts 02215, USA.
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Haspel
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, 75 Francis Street, Boston, Massachusetts 02215, USA.
authors.forename: Sukrutha
authors.initials: S
authors.lastname: Chettimada
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, 75 Francis Street, Boston, Massachusetts 02215, USA.
authors.forename: Rahamthulla S
authors.initials: RS
authors.lastname: Shaik
authors.affiliation: Channing Division of Network Medicine, Brigham and Women's Hospital, 181 Longwood Avenue, Boston, Massachusetts 02215, USA.
authors.forename: Jen-Hwa
authors.initials: JH
authors.lastname: Chu
authors.affiliation: 1] Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, 75 Francis Street, Boston, Massachusetts 02215, USA [2] Channing Division of Network Medicine, Brigham and Women's Hospital, 181 Longwood Avenue, Boston, Massachusetts 02215, USA.
authors.forename: Benjamin A
authors.initials: BA
authors.lastname: Raby
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, 75 Francis Street, Boston, Massachusetts 02215, USA.
authors.forename: Manuela
authors.initials: M
authors.lastname: Cernadas
authors.affiliation: Channing Division of Network Medicine, Brigham and Women's Hospital, 181 Longwood Avenue, Boston, Massachusetts 02215, USA.
authors.forename: Vincent
authors.initials: V
authors.lastname: Carey
authors.affiliation: Channing Division of Network Medicine, Brigham and Women's Hospital, 181 Longwood Avenue, Boston, Massachusetts 02215, USA.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Process
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, 75 Francis Street, Boston, Massachusetts 02215, USA.
authors.forename: G Matthew
authors.initials: GM
authors.lastname: Hunninghake
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, 75 Francis Street, Boston, Massachusetts 02215, USA.
authors.forename: Emeka
authors.initials: E
authors.lastname: Ifedigbo
authors.affiliation: Department of Surgery, Brigham and Women's Hospital, 75 Francis Street, Boston, Massachusetts 02215, USA.
authors.forename: James A
authors.initials: JA
authors.lastname: Lederer
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, 75 Francis Street, Boston, Massachusetts 02215, USA.
authors.forename: Joshua
authors.initials: J
authors.lastname: Englert
authors.affiliation: Department of Pathology, Brigham and Women's Hospital, 75 Francis Street, Boston, Massachusetts 02215, USA.
authors.forename: Ashley
authors.initials: A
authors.lastname: Pelton
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, 75 Francis Street, Boston, Massachusetts 02215, USA.
authors.forename: Anna
authors.initials: A
authors.lastname: Coronata
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, 75 Francis Street, Boston, Massachusetts 02215, USA.
authors.forename: Laura E
authors.initials: LE
authors.lastname: Fredenburgh
authors.affiliation: Department of Medicine, New York Presbyterian/Weill Cornell Medical Center, 555 East 68 Street, New York, New York, 10065, USA.
authors.forename: Augustine M K
authors.initials: AM
authors.lastname: Choi
mesh_terms: D000818:Animals; D056926:CLOCK Proteins / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D002940:Circadian Rhythm / Q000235:genetics* / Q000276:immunology; D056925:Circadian Rhythm Signaling Peptides and Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D004731:Endotoxins / Q000633:toxicity; D005786:Gene Expression Regulation; D006098:Granulocytes / Q000276:immunology; D007958:Leukocyte Count; D008168:Lung / Q000276:immunology / Q000378:metabolism*; D008214:Lymphocytes / Q000276:immunology; D051379:Mice; D011014:Pneumonia / Q000139:chemically induced / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism*
chemical_list: D056925:Circadian Rhythm Signaling Peptides and Proteins; D004731:Endotoxins; D012333:RNA, Messenger; D056926:CLOCK Proteins