title: Exogenous melatonin inhibits neutrophil migration through suppression of ERK activation.
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 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 the epidermal growth factor 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 of 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.
authors: Chinese Academy of Sciences Key Laboratory of Brain Function and DiseaseSchool of Life Sciences, University of Science and Technology of China, No. 96 Jinzhai Road, Hefei, Anhui Province 230026, People's Republic of China.
authors: Da-Long
authors: DL
authors: Ren
authors: Chinese Academy of Sciences Key Laboratory of Brain Function and DiseaseSchool of Life Sciences, University of Science and Technology of China, No. 96 Jinzhai Road, Hefei, Anhui Province 230026, People's Republic of China.
authors: Ai-Ai
authors: AA
authors: Sun
authors: Chinese Academy of Sciences Key Laboratory of Brain Function and DiseaseSchool of Life Sciences, University of Science and Technology of China, No. 96 Jinzhai Road, Hefei, Anhui Province 230026, People's Republic of China.
authors: Ya-Juan
authors: YJ
authors: Li
authors: Chinese Academy of Sciences Key Laboratory of Brain Function and DiseaseSchool of Life Sciences, University of Science and Technology of China, No. 96 Jinzhai Road, Hefei, Anhui Province 230026, People's Republic of China.
authors: Min
authors: M
authors: Chen
authors: Chinese Academy of Sciences Key Laboratory of Brain Function and DiseaseSchool of Life Sciences, University of Science and Technology of China, No. 96 Jinzhai Road, Hefei, Anhui Province 230026, People's Republic of China.
authors: Shu-Chao
authors: SC
authors: Ge
authors: Chinese Academy of Sciences Key Laboratory of Brain Function and DiseaseSchool of Life Sciences, University of Science and Technology of China, No. 96 Jinzhai Road, Hefei, Anhui Province 230026, People's Republic of China bhu@ustc.edu.cn.
authors: Bing
authors: B
authors: Hu
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D005260:Female; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006824:Hybridization, Genetic; D007113:Immunity, Innate / Q000187:drug effects; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D008550:Melatonin / Q000378:metabolism*; D009113:Muramidase / Q000235:genetics / Q000378:metabolism; D018375:Neutrophil Activation / Q000187:drug effects; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D011401:Promoter Regions, Genetic; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D057705:Transendothelial and Transepithelial Migration / Q000187:drug effects*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics / Q000378:metabolism; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism
chemical_list: D008164:Luminescent Proteins; D047428:Protein Kinase Inhibitors; D011993:Recombinant Fusion Proteins; D029961:Zebrafish Proteins; C485184:enhanced green fluorescent protein; C413663:fluorescent protein 583; D049452:Green Fluorescent Proteins; D040301:Vascular Endothelial Growth Factor Receptor-2; C000595917:kdr protein, zebrafish; D009113:Muramidase; C466103:lyz protein, zebrafish; D008550:Melatonin
keywords: MAPK/ERK; injury; melatonin; migration; neutrophil; zebrafish