title: Screening the Impact of Sirtuin Inhibitors on Inflammatory and Innate Immune Responses of Macrophages and in a Mouse Model of Endotoxic Shock.
abstract: The development and screening of pharmacological modulators of histone deacetylases (HDACs), and particularly sirtuins, is a promising field for the identification of new drugs susceptible to be used for treatment strategies in a large array of welfare-associated, autoimmune and oncologic diseases. Here we describe a comprehensive protocol to evaluate the impact of sirtuin-targeting drugs on inflammatory and innate immune responses in vitro and in a preclinical mouse model of endotoxemia. We first provide an overview on strategies to design in vitro experiments, then focus on the analysis of cytokine production by primary macrophages and RAW 267.7 macrophages at the mRNA and protein levels, and finally describe the setup and follow-up of a mouse model of inflammation-driven endotoxic shock.
authors.affiliation: Infectious Diseases Service, Department of Medicine, Centre Hospitalier Universitaire Vaudois and University of Lausanne, CLED.04.407, Chemin des Boveresses 155, CH-1066, Epalinges, Switzerland.
authors.forename: Eleonora
authors.initials: E
authors.lastname: Ciarlo
authors.affiliation: Infectious Diseases Service, Department of Medicine, Centre Hospitalier Universitaire Vaudois and University of Lausanne, CLED.04.407, Chemin des Boveresses 155, CH-1066, Epalinges, Switzerland. Thierry.Roger@chuv.ch.
authors.forename: Thierry
authors.initials: T
authors.lastname: Roger
mesh_terms: D000818:Animals; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D005786:Gene Expression Regulation / Q000187:drug effects; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D007113:Immunity, Innate / Q000187:drug effects*; D008264:Macrophages / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D051379:Mice; D000067996:RAW 264.7 Cells; D012772:Shock, Septic / Q000188:drug therapy* / Q000276:immunology; D037761:Sirtuins / Q000378:metabolism
chemical_list: D016207:Cytokines; D056572:Histone Deacetylase Inhibitors; D037761:Sirtuins
keywords: Cytokine; Endotoxemia; Epigenetics; Histone deacetylases; Innate immunity; Macrophage; Pharmacological inhibitors; Sepsis; Sirtuins