PUBLICATION

The Involvement of Cholesterol in Sepsis and Tolerance to Lipopolysaccharide Highlighted by the Transcriptome Analysis of Zebrafish (Danio rerio)

Authors
Dios, S., Balseiro, P., Costa, M.M., Romero, A., Boltaña, S., Roher, N., Mackenzie, S., Figueras, A., Novoa, B.
ID
ZDB-PUB-140903-3
Date
2014
Source
Zebrafish   11(5): 421-33 (Journal)
Registered Authors
Figueras, Antonio, Novoa, Beatriz
Keywords
none
MeSH Terms
  • Animals
  • Escherichia coli/physiology
  • Fish Proteins/genetics*
  • Fish Proteins/metabolism
  • Lipopolysaccharides/metabolism*
  • Pseudomonas aeruginosa/physiology
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sepsis/genetics*
  • Sepsis/immunology
  • Sepsis/microbiology*
  • Transcriptome*
  • Zebrafish/genetics*
  • Zebrafish/immunology
  • Zebrafish/metabolism
PubMed
25181277 Full text @ Zebrafish
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.
Genes / Markers
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping