Exp Mol Med.
2013 Jun;45(6):e27.
Wnt5a stimulates chemotactic migration and chemokine production in human neutrophils
- Affiliations
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- 1Department of Biological Science, Sungkyunkwan University, Suwon, South Korea. yoesik@skku.edu
- 2Mitochondria Hub Regulation Center, Dong-A University, Busan, South Korea.
- 3Department of Hematology-Oncology, Ajou University School of Medicine, Suwon, South Korea.
- 4School of Nano-Biotechnology and Chemical Engineering, Ulsan National Institute of Science and Technology, Ulsan, South Korea.
- 5Samsung Advanced Institute for Health Sciences and Technology, Sungkyunkwan University, Seoul, South Korea.
Abstract
- Wnt5a is a ligand that activates the noncanonical Wnt signaling pathways (beta-catenin-independent pathways). Human neutrophils expressed several Wnt5a receptors, such as Frizzled 2, 5 and 8. Stimulation of human neutrophils with Wnt5a caused chemotactic migration and the production of two important chemokines, CXCL8 and CCL2. CCL2 production by Wnt5a was mediated by a pertussis toxin-sensitive G-protein-dependent pathway. Wnt5a also stimulated the phosphorylation of three mitogen-activated protein kinases (MAPKs: ERK, p38 MAPK and JNK) and Akt. Inhibition of ERK, p38 MAPK or JNK by specific inhibitors induced a dramatic reduction in Wnt5a-induced CCL2 production. Supernatant collected from lipopolysaccharide-stimulated macrophages induced neutrophil chemotaxis, which was significantly inhibited by anti-Wnt5a antibody. Our results suggested that Wnt5a may contribute to neutrophil recruitment, mediating the inflammation response.
Keyword
MeSH Terms
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Activating Transcription Factor 2/metabolism
Animals
Cell Separation
Chemokines/*biosynthesis
Chemotaxis/*drug effects
Culture Media, Conditioned/pharmacology
Extracellular Signal-Regulated MAP Kinases/metabolism
GTP-Binding Proteins/metabolism
Humans
JNK Mitogen-Activated Protein Kinases/metabolism
Lipopolysaccharides/pharmacology
Macrophages/drug effects/metabolism
Mice
NF-kappa B/metabolism
Neutrophils/*cytology/drug effects/enzymology/*metabolism
Pertussis Toxin/pharmacology
Phosphatidylinositol 3-Kinases/metabolism
Proto-Oncogene Proteins c-akt/metabolism
Receptors, Wnt/metabolism
Type C Phospholipases/metabolism
Wnt Proteins/*pharmacology
p38 Mitogen-Activated Protein Kinases/metabolism
Activating Transcription Factor 2
Chemokines
Culture Media, Conditioned
Lipopolysaccharides
NF-kappa B
Receptors, Wnt
Wnt Proteins
Pertussis Toxin
Phosphatidylinositol 3-Kinases
Proto-Oncogene Proteins c-akt
Extracellular Signal-Regulated MAP Kinases
JNK Mitogen-Activated Protein Kinases
p38 Mitogen-Activated Protein Kinases
Type C Phospholipases
GTP-Binding Proteins
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