title: Epigenetic coordination of acute systemic inflammation: potential therapeutic targets.
abstract: Epigenetic reprogramming of thousands of genes directs the course of acute systemic inflammation, which is highly lethal when dysregulated during sepsis. No molecular-based treatments for sepsis are available. A new concept supports that sepsis is an immunometabolic disease and that loss of control of nuclear epigenetic regulator sirtuin 1 (SIRT-1), a NAD(+) sensor directs immune and metabolic pathways during sepsis. SIRT-1, acting as homeostasis checkpoint, controls hyper- and hypo-inflammatory responses of sepsis at the microvascular interface, which disseminates inflammatory injury to cause multiple organ failure. Modifying SIRT-1 activity, which can prevent or treat established sepsis in mice, may provide a new way to treat sepsis by epigenetically restoring immunometabolic homeostasis.
authors.affiliation: Department of Anesthesiology, Section on Critical Care, Wake Forest School of Medicine, Medical Center Blvd, Winston-Salem, NC 27157, USA.
authors.forename: Vidula
authors.initials: V
authors.lastname: Vachharajani
authors.forename: Tiefu
authors.initials: T
authors.lastname: Liu
authors.forename: Charles E
authors.initials: CE
authors.lastname: McCall
mesh_terms: D000818:Animals; D002199:Capillary Permeability / Q000276:immunology; D004195:Disease Models, Animal; D044127:Epigenesis, Genetic / Q000276:immunology*; D006706:Homeostasis / Q000276:immunology; D006801:Humans; D056747:Immunomodulation; D007249:Inflammation / Q000276:immunology* / Q000628:therapy; D055442:Metabolome; D051379:Mice; D058990:Molecular Targeted Therapy; D018805:Sepsis / Q000276:immunology* / Q000628:therapy; D056564:Sirtuin 1 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*
chemical_list: C447939:SIRT1 protein, human; D056564:Sirtuin 1
keywords: SIRT-1; acute inflammation; epigenetics; immunometabolism; leukocyte adhesion; microvascular dysfunction; sepsis
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