PUBLICATION
Development and Characterization of an Endotoxemia Model in Zebra Fish
- Authors
- Hsu, A.Y., Gurol, T., Sobreira, T.J.P., Zhang, S., Moore, N., Cai, C., Zhang, Z.Y., Deng, Q.
- ID
- ZDB-PUB-180418-33
- Date
- 2018
- Source
- Frontiers in immunology 9: 607 (Journal)
- Registered Authors
- Deng, Qing, Gurol, Theodore, Hsu, Alan
- Keywords
- endotoxemia, endotoxin, inflammation, innate immunity, lipopolysaccharide, zebra fish
- MeSH Terms
-
- Zebrafish/immunology*
- Endotoxemia/immunology*
- Humans
- Myeloid Differentiation Factor 88/antagonists & inhibitors
- Cells, Cultured
- Immunity, Innate*
- Fish Proteins/antagonists & inhibitors
- Gene Expression Profiling
- Animals
- Blood Circulation
- Cell Movement
- Disease Models, Animal*
- Hematopoiesis
- Protein Tyrosine Phosphatase, Non-Receptor Type 11/antagonists & inhibitors
- Immunity, Cellular
- Signal Transduction
- Inflammation/immunology*
- Lipopolysaccharides/administration & dosage
- PubMed
- 29651289 Full text @ Front Immunol
Citation
Hsu, A.Y., Gurol, T., Sobreira, T.J.P., Zhang, S., Moore, N., Cai, C., Zhang, Z.Y., Deng, Q. (2018) Development and Characterization of an Endotoxemia Model in Zebra Fish. Frontiers in immunology. 9:607.
Abstract
Endotoxemia is a condition in which endotoxins enter the blood stream and cause systemic and sometimes lethal inflammation. Zebra fish provides a genetically tractable model organism for studying innate immunity, with additional advantages in live imaging and drug discovery. However, a bona fide endotoxemia model has not been established in zebra fish. Here, we have developed an acute endotoxemia model in zebra fish by injecting a single dose of LPS directly into the circulation. Hallmarks of human acute endotoxemia, including systemic inflammation, extensive tissue damage, circulation blockade, immune cell mobilization, and emergency hematopoiesis, were recapitulated in this model. Knocking out the adaptor protein Myd88 inhibited systemic inflammation and improved zebra fish survival. In addition, similar alternations of pathways with human acute endotoxemia were detected using global proteomic profiling and MetaCore™ pathway enrichment analysis. Furthermore, treating zebra fish with a protein tyrosine phosphatase nonreceptor type 11 (Shp2) inhibitor decreased systemic inflammation, immune mobilization, tissue damage, and improved survival in the endotoxemia model. Together, we have established and characterized the phenotypic and gene expression changes of a zebra fish endotoxemia model, which is amenable to genetic and pharmacological discoveries that can ultimately lead to a better mechanistic understanding of the dynamics and interplay of the innate immune system.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping