title: The involvement of cholesterol in sepsis and tolerance to lipopolysaccharide highlighted by the transcriptome analysis of zebrafish (Danio rerio).
abstract: Septic shock is the most common cause of death in intensive care units due to an aggressive inflammatory response that leads to multiple organ failure. However, a lipopolysaccharide (LPS) tolerance phenomenon (a nonreaction to LPS), is also often described. Neither the inflammatory response nor the tolerance is completely understood. In this work, both of these responses were analyzed using microarrays in zebrafish. Fish that were 4 or 6 days postfertilization (dpf) and received a lethal dose (LD) of LPS exhibited 100% mortality in a few days. Their transcriptome profile, even at 4 dpf, resembled the profile in humans with severe sepsis. Moreover, we selected 4-dpf fish to set up a tolerance protocol: fish treated with a nonlethal concentration of Escherichia coli LPS exhibited complete protection against the LD of LPS. Most of the main inflammatory molecules described in mammals were represented in the zebrafish microarray experiments. Additionally and focusing on this tolerance response, the use of cyclodextrins may mobilize cholesterol reservoirs to decrease mortality after a LD dose of LPS. Therefore, it is possible that the use of the whole animal could provide some clues to enhance the understanding of the inflammatory/tolerance response and to guide drug discovery.
authors.affiliation: 1 Instituto de Investigaciones Marinas (IIM)-Consejo Superior de Investigaciones Científicas (CSIC) , Vigo, Spain .
authors.forename: Sonia
authors.initials: S
authors.lastname: Dios
authors.forename: Pablo
authors.initials: P
authors.lastname: Balseiro
authors.forename: Maria M
authors.initials: MM
authors.lastname: Costa
authors.forename: Alejandro
authors.initials: A
authors.lastname: Romero
authors.forename: Sebastián
authors.initials: S
authors.lastname: Boltaña
authors.forename: Nerea
authors.initials: N
authors.lastname: Roher
authors.forename: Simon
authors.initials: S
authors.lastname: Mackenzie
authors.forename: Antonio
authors.initials: A
authors.lastname: Figueras
authors.forename: Beatriz
authors.initials: B
authors.lastname: Novoa
mesh_terms: D000818:Animals; D004926:Escherichia coli / Q000502:physiology; D029941:Fish Proteins / Q000235:genetics* / Q000378:metabolism; D008070:Lipopolysaccharides / Q000378:metabolism*; D011550:Pseudomonas aeruginosa / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018805:Sepsis / Q000235:genetics* / Q000276:immunology / Q000382:microbiology*; D059467:Transcriptome; D015027:Zebrafish / Q000235:genetics* / Q000276:immunology / Q000378:metabolism
chemical_list: D029941:Fish Proteins; D008070:Lipopolysaccharides