PUBLICATION
Exogenous melatonin inhibits neutrophil migration through suppression of ERK activation
- Authors
- Ren, D.L., Sun, A.A., Li, Y.J., Chen, M., Ge, S.C., Hu, B.
- ID
- ZDB-PUB-150826-6
- Date
- 2015
- Source
- The Journal of endocrinology 227(1): 49-60 (Journal)
- Registered Authors
- Hu, Bing
- Keywords
- melatonin, neutrophil, injury, MAPK/ERK, migration, zebrafish
- MeSH Terms
-
- MAP Kinase Signaling System*/drug effects
- Neutrophil Activation*/drug effects
- Protein Kinase Inhibitors/pharmacology
- Muramidase/genetics
- Muramidase/metabolism
- Neutrophils/drug effects
- Neutrophils/immunology
- Neutrophils/metabolism*
- Vascular Endothelial Growth Factor Receptor-2/genetics
- Vascular Endothelial Growth Factor Receptor-2/metabolism
- Green Fluorescent Proteins/genetics
- Green Fluorescent Proteins/metabolism
- Animals, Genetically Modified
- Promoter Regions, Genetic
- Protein Processing, Post-Translational/drug effects
- Recombinant Fusion Proteins/genetics
- Recombinant Fusion Proteins/metabolism
- Transendothelial and Transepithelial Migration/drug effects*
- Hybridization, Genetic
- Immunity, Innate*/drug effects
- Melatonin/metabolism*
- Phosphorylation/drug effects
- Luminescent Proteins/genetics
- Luminescent Proteins/metabolism
- Zebrafish Proteins/antagonists & inhibitors
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism
- Female
- Male
- Zebrafish
- Animals
- PubMed
- 26303298 Full text @ J. Endocrinol.
Citation
Ren, D.L., Sun, A.A., Li, Y.J., Chen, M., Ge, S.C., Hu, B. (2015) Exogenous melatonin inhibits neutrophil migration through suppression of ERK activation. The Journal of endocrinology. 227(1):49-60.
Abstract
Neutrophil migration to inflammatory sites is the fundamental process of innate immunity among organisms against pathogen invasion. As a major sleep adjusting hormone, melatonin has also been proved to be involved in various inflammatory events. This study aimed to evaluate the impact of exogenous melatonin on neutrophil migration to the injury site in live zebrafish and further investigate whether extracellular-signal-regulated kinase (ERK) signaling is involved in this process. Using the tail fin transection model, the fluorescently labeled neutrophil was in vivo visualized in transgenic Tg(lyz:EGFP), Tg(lyz:DsRed) zebrafish. We found that exogenous melatonin administration dramatically inhibited the injury-induced neutrophil migration in a dose-dependent and time-dependent manner. The inhibited effect of melatonin on neutrophil migration could be attenuated by melatonin receptor 1, 2, and 3 antagonists. The ERK phosphorylation level was significantly decreased post injury when treated with melatonin. The blocking of ERK activation with inhibitor PD0325901 suppressed the number of migrated neutrophils in response to injury. However, the activation of ERK with EGF could impair the inhibited effect of melatonin on neutrophil migration. We also detected that PD0325901 significantly suppressed the in vivo neutrophils transmigrating over the vessel endothelial cell using the transgenic Tg(flk:EGFP);(lyz:DsRed) line labeled as both vessel and neutrophil. Taking all these data together, the results indicated that exogenous melatonin had an anti-migratory effect on neutrophils by blocking the ERK phosphorylation signal, and it led to the subsequent adhesion molecule expression. Thus, the crossing of the vessel endothelial cells of neutrophils became difficult.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping