Molecular mechanisms of innate memory and tolerance to LPS

• Published in: Journal of leukocyte biology Vol. 101; no. 1; pp. 107 - 119
• Main Authors: Seeley, John J., Ghosh, Sankar
• Format: Journal Article
• Language: English
• Published: United States Oxford University Press 01.01.2017
• Subjects: Animals; chromatin; Chromatin remodeling; Disseminated infection; DNA Methylation - genetics; endotoxin; Epigenetics; Exposure; Gene expression; Humans; Immune Tolerance - immunology; Immunity, Innate; Immunologic Memory; Inflammation; Inflammatory response; lipopolysaccharide; Lipopolysaccharides; Lipopolysaccharides - immunology; Macrophages; Molecular modelling; Signal transduction; Signaling; Toll-Like Receptors - metabolism; chromatin; lipopolysaccharide; inflammation; epigenetics; endotoxin
• ISSN: 0741-5400; 1938-3673
• DOI: 10.1189/jlb.3MR0316-118RR

LPS is a potent trigger of macrophage‐mediated inflammation. However, prolonged exposure to LPS induces a state of tolerance that reprograms the inflammatory response, resulting in reduced inflammatory cytokine production in vitro and in vivo. Recent evidence suggests that LPS tolerance also increases the expression of a subset of genes that may protect animals from systemic infection while they are in the tolerized state. However, a molecular basis for these selective changes in inflammatory gene expression during LPS tolerance has remained elusive. In this review, we discuss the molecular mechanisms that may account for these effects, focusing on changes in LPS signaling, epigenetic markers, and chromatin remodeling that may be responsible for cellular memory and physiologic changes that comprise the LPS tolerance phenomenon. Review on how exposure to LPS alters signal transduction, chromatin organization, and gene expression to subsequent inflammatory stimulation.