PUBLICATION
Class III antiarrhythmic methanesulfonanilides inhibit leukocyte recruitment in zebrafish
- Authors
- Brown, S.B., Tucker, C.S., Ford, C., Lee, Y., Dunbar, D.R., and Mullins, J.J.
- ID
- ZDB-PUB-070427-13
- Date
- 2007
- Source
- Journal of Leukocyte Biology 82(1): 79-84 (Journal)
- Registered Authors
- Keywords
- inflammation, infection, ether-à-go-go-related gene (ERG)
- MeSH Terms
-
- Anilides/pharmacology*
- Animals
- Anti-Arrhythmia Agents/pharmacology*
- Cell Adhesion
- Chemotaxis, Leukocyte/drug effects*
- Disease Models, Animal
- Embryo, Nonmammalian
- Ether-A-Go-Go Potassium Channels/antagonists & inhibitors
- Ether-A-Go-Go Potassium Channels/genetics
- Ether-A-Go-Go Potassium Channels/physiology*
- Heart Rate
- Inflammation/drug therapy
- Inflammation/immunology*
- RNA, Antisense/pharmacology*
- RNA, Antisense/therapeutic use
- Wound Infection/immunology
- Wound Infection/pathology
- Zebrafish
- PubMed
- 17431092 Full text @ J. Leukoc. Biol.
Citation
Brown, S.B., Tucker, C.S., Ford, C., Lee, Y., Dunbar, D.R., and Mullins, J.J. (2007) Class III antiarrhythmic methanesulfonanilides inhibit leukocyte recruitment in zebrafish. Journal of Leukocyte Biology. 82(1):79-84.
Abstract
Understanding fundamental molecular mechanisms that govern the transmigration and interstitial migration of leukocytes to sites of tissue damage and infection is of potential significance in identifying novel therapeutic targets for the management of chronic inflammatory disorders. CD31 is a mammalian cell adhesion molecule that regulates the recruitment of leukocytes from the circulation. Our recent unpublished work has suggested that homophilic ligation of CD31 can negatively regulate the ether-a-go-go-related gene (ERG) current within leukocytes to regulate cell-cell adhesion. To validate and probe the functional significance of ERG in leukocytes, we developed an infected wound model of inflammation in zebrafish and assessed the efficacy of two ERG-specific inhibitors, dofetilide and E4031, as well as an ERG-specific antisense RNA morpholino on neutrophil recruitment. Our data confirm a hitherto undescribed role for ERG in leukocytes, where inhibition or translational knockdown of ERG resulted in significant attenuation of the inflammatory response to an infectious stimulus. Inhibition of ERG was verified independently by a decrease in the ventricular heart rate, where ERG also functions in the repolarization of the cardiac action potential. Our results suggest that ERG-specific Class III antiarrhythmic drugs can modulate inflammatory responses to infection.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping