title: Tolerization of inflammatory gene expression.
abstract: Lipopolysaccharide (LPS) is a potent inducer of inflammation. However, in a phenomenon known as LPS tolerance, prolonged exposure to LPS reprograms the host response to subsequent LPS reexposure. Proinflammatory cytokine production is suppressed, while production of antimicrobial genes is increased. In vivo models suggest that LPS tolerance dramatically reduces susceptibility to septic shock, while keeping the capacity for clearance of certain pathogens intact. These observations imply that artificial induction of tolerance may be an attractive means to intervene in the progression of sepsis and other inflammatory diseases. However, the underlying mechanisms that govern the tolerogenic response remain poorly understood, hindering efforts to evaluate LPS tolerance induction as a therapeutic approach. Recent advances indicate that chromatin modifications and microRNA mediators may be particularly important in the tolerogenic response. In this review, we discuss possible mechanisms to account for the phenomenon of LPS tolerance, with particular emphasis on the role of newly identified mediators.
authors.affiliation: Department of Microbiology & Immunology, Columbia University, College of Physicians and Surgeons, New York, New York 10032.
authors.forename: John J
authors.initials: JJ
authors.lastname: Seeley
authors.affiliation: Department of Microbiology & Immunology, Columbia University, College of Physicians and Surgeons, New York, New York 10032 sg2715@columbia.edu.
authors.forename: Sankar
authors.initials: S
authors.lastname: Ghosh
mesh_terms: D000818:Animals; D000890:Anti-Infective Agents / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D002843:Chromatin / Q000378:metabolism; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006657:Histones / Q000378:metabolism; D006801:Humans; D007108:Immune Tolerance; D007249:Inflammation / Q000473:pathology*; D008070:Lipopolysaccharides / Q000378:metabolism*; D035683:MicroRNAs / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D011401:Promoter Regions, Genetic; D015398:Signal Transduction; D051197:Toll-Like Receptor 4 / Q000378:metabolism
chemical_list: D000890:Anti-Infective Agents; D002843:Chromatin; D006657:Histones; D008070:Lipopolysaccharides; D035683:MicroRNAs; D016328:NF-kappa B; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4