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Transcription profiling of peripheral blood monocyte derived macrophages treated or not with synthetic REVERB ligand GSK-4112.

ABSTRACT: Circadian biology regulates inflammatory responses in mice via the clock protein REVERBα, resulting in altered mortality and morbidity. The influence of this immune-modulation pathway in humans is unclear, but may affect outcomes after transplant. We sought to determine whether the circadian clock affects primary graft dysfunction after lung transplantation, and the role of the clock protein REVERBα. In this study we investigated the action of a synthetic REVERB ligand, (GSK4112) in human monocyte-derived macrophages.

ORGANISM(S): Homo sapiens

SUBMITTER: Leo Zeef

PROVIDER: E-MTAB-6478 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Incidence of primary graft dysfunction after lung transplantation is altered by timing of allograft implantation.

Cunningham Peter S PS Maidstone Robert R Durrington Hannah J HJ Venkateswaran Rajamayier V RV Cypel Marcelo M Keshavjee Shaf S Gibbs Julie E JE Loudon Andrew S AS Chow Chung-Wai CW Ray David W DW Blaikley John F JF

Thorax 20181009 4

The importance of circadian factors in managing patients is poorly understood. We present two retrospective cohort studies showing that lungs reperfused between 4 and 8 AM have a higher incidence (OR 1.12; 95% CI 1.03 to 1.21; p=0.01) of primary graft dysfunction (PGD) in the first 72 hours after transplantation. Cooling of the donor lung, occurring during organ preservation, shifts the donor circadian clock causing desynchrony with the recipient. The clock protein REV-ERBα directly regulates PG ...[more]

PMID: 30301818

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