Epigenetics, bioenergetics, and microRNA coordinate gene-specific reprogramming during acute systemic inflammation

Journal of Leukocyte Biology

Tiefu Liu⁵  Barbara Yoza–¹  Charles E. McCall ⁴  Mohamed El Gazzar³  Vidula Vachharajani and² 

[1] –General Surgery, Division of Surgical Sciences, Wake Forest University School of Medicine, Winston Salem, North Carolina, USA;Anesthesiology, and –General Surgery, Division of Surgical Sciences, Wake Forest University School of Medicine, Winston Salem, North Carolina, USA;Department of Internal Medicine, East Tennessee University College of Medicine, Johnson City, Tennessee, USA –General Surgery, Division of Surgical Sciences, Wake Forest University School of Medicine, Winston Salem, North Carolina, USA;Translational Science Institute and Departments of  Internal Medicine, Section on Molecular Medicine, –General Surgery, Division of Surgical Sciences, Wake Forest University School of Medicine, Winston Salem, North Carolina, USA;Departments of  Internal Medicine, Section on Molecular Medicine, –General Surgery, Division of Surgical Sciences, Wake Forest University School of Medicine, Winston Salem, North Carolina, USA;

关键词: chromatin remodeling;    endotoxin tolerance;    facultative heterochromatin;    NAD⁺;    Nampt;    p65;    RelB;    sepsis;    sirtuin 1;    Toll-like receptors;   

DOI  :  10.1189/jlb.0211075

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

Acute systemic inflammation from infectious and noninfectious etiologies has stereotypic features that progress through an initiation (proinflammatory) phase, an adaptive (anti-inflammatory) phase, and a resolution (restoration of homeostasis) phase. These phase-shifts are accompanied by profound and predictable changes in gene expression and metabolism. Here, we review the emerging concept that the temporal phases of acute systemic inflammation are controlled by an integrated bioenergy and epigenetic bridge that guides the timing of transcriptional and post-transcriptional processes of specific gene sets. This unifying connection depends, at least in part, on redox sensor NAD+-dependent deacetylase, Sirt1, and a NF-κB-dependent p65 and RelB feed-forward and gene-specific pathway that generates silent facultative heterochromatin and active euchromatin. An additional level of regulation for gene-specific reprogramming is generated by differential expression of miRNA that directly and indirectly disrupts translation of inflammatory genes. These molecular reprogramming circuits generate a dynamic chromatin landscape that temporally defines the course of acute inflammation.

【 授权许可】

Unknown