期刊
EXPERT REVIEW OF CLINICAL IMMUNOLOGY
卷 10, 期 9, 页码 1141-1150出版社
TAYLOR & FRANCIS LTD
DOI: 10.1586/1744666X.2014.943192
关键词
acute inflammation; epigenetics; immunometabolism; leukocyte adhesion; microvascular dysfunction; sepsis; SIRT-1
类别
资金
- NIH [R01GM099807, R01AI065791, R01AI079144]
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.
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