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Activation of the JAK/STAT3 and PI3K/AKT pathways are crucial for IL-6 trans-signaling-mediated pro-inflammatory response in human vascular endothelial cells
by
Ljungberg, Liza U.
, Fälker, Knut
, Paramel, Geena
, Kumawat, Ashok K.
, Zegeye, Mulugeta M.
, Grenegård, Magnus
, Lindkvist, Madelene
, Sirsjö, Allan
in
1-Phosphatidylinositol 3-kinase
/ AKT protein
/ Antibiotics
/ Atherosclerosis
/ Biomedical and Life Sciences
/ Cell Biology
/ Cytokines
/ Cytokines and Growth Factors
/ Development and progression
/ Endothelial cells
/ Endothelium
/ Enzyme-linked immunosorbent assay
/ Flow cytometry
/ Gene expression
/ Genetic aspects
/ Glycoprotein gp130
/ HUVECs
/ Idrott med inriktning mot didaktik
/ Inflammation
/ Interleukin 6
/ Interleukin 6 receptors
/ Interleukin-6 signaling
/ Life Sciences
/ Metabolic pathways
/ Monocyte chemoattractant protein
/ Monocyte chemoattractant Protein-1
/ Monocytes
/ Phosphorylation
/ Physical Education and Sport Pedagogy
/ Physiological aspects
/ Pro-inflammatory cytokines
/ Protein-Ligand Interactions
/ Proteins
/ Receptors
/ Rodents
/ Signal transduction
/ Stat3 protein
/ Tumor necrosis factor-TNF
/ Umbilical vein
2018
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Activation of the JAK/STAT3 and PI3K/AKT pathways are crucial for IL-6 trans-signaling-mediated pro-inflammatory response in human vascular endothelial cells
by
Ljungberg, Liza U.
, Fälker, Knut
, Paramel, Geena
, Kumawat, Ashok K.
, Zegeye, Mulugeta M.
, Grenegård, Magnus
, Lindkvist, Madelene
, Sirsjö, Allan
in
1-Phosphatidylinositol 3-kinase
/ AKT protein
/ Antibiotics
/ Atherosclerosis
/ Biomedical and Life Sciences
/ Cell Biology
/ Cytokines
/ Cytokines and Growth Factors
/ Development and progression
/ Endothelial cells
/ Endothelium
/ Enzyme-linked immunosorbent assay
/ Flow cytometry
/ Gene expression
/ Genetic aspects
/ Glycoprotein gp130
/ HUVECs
/ Idrott med inriktning mot didaktik
/ Inflammation
/ Interleukin 6
/ Interleukin 6 receptors
/ Interleukin-6 signaling
/ Life Sciences
/ Metabolic pathways
/ Monocyte chemoattractant protein
/ Monocyte chemoattractant Protein-1
/ Monocytes
/ Phosphorylation
/ Physical Education and Sport Pedagogy
/ Physiological aspects
/ Pro-inflammatory cytokines
/ Protein-Ligand Interactions
/ Proteins
/ Receptors
/ Rodents
/ Signal transduction
/ Stat3 protein
/ Tumor necrosis factor-TNF
/ Umbilical vein
2018
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Activation of the JAK/STAT3 and PI3K/AKT pathways are crucial for IL-6 trans-signaling-mediated pro-inflammatory response in human vascular endothelial cells
by
Ljungberg, Liza U.
, Fälker, Knut
, Paramel, Geena
, Kumawat, Ashok K.
, Zegeye, Mulugeta M.
, Grenegård, Magnus
, Lindkvist, Madelene
, Sirsjö, Allan
in
1-Phosphatidylinositol 3-kinase
/ AKT protein
/ Antibiotics
/ Atherosclerosis
/ Biomedical and Life Sciences
/ Cell Biology
/ Cytokines
/ Cytokines and Growth Factors
/ Development and progression
/ Endothelial cells
/ Endothelium
/ Enzyme-linked immunosorbent assay
/ Flow cytometry
/ Gene expression
/ Genetic aspects
/ Glycoprotein gp130
/ HUVECs
/ Idrott med inriktning mot didaktik
/ Inflammation
/ Interleukin 6
/ Interleukin 6 receptors
/ Interleukin-6 signaling
/ Life Sciences
/ Metabolic pathways
/ Monocyte chemoattractant protein
/ Monocyte chemoattractant Protein-1
/ Monocytes
/ Phosphorylation
/ Physical Education and Sport Pedagogy
/ Physiological aspects
/ Pro-inflammatory cytokines
/ Protein-Ligand Interactions
/ Proteins
/ Receptors
/ Rodents
/ Signal transduction
/ Stat3 protein
/ Tumor necrosis factor-TNF
/ Umbilical vein
2018
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Activation of the JAK/STAT3 and PI3K/AKT pathways are crucial for IL-6 trans-signaling-mediated pro-inflammatory response in human vascular endothelial cells
Journal Article
Activation of the JAK/STAT3 and PI3K/AKT pathways are crucial for IL-6 trans-signaling-mediated pro-inflammatory response in human vascular endothelial cells
2018
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Overview
Background
IL-6 classic signaling is linked to anti-inflammatory functions while the trans-signaling is associated with pro-inflammatory responses. Classic signaling is induced via membrane-bound IL-6 receptor (IL-6R) whereas trans-signaling requires prior binding of IL-6 to the soluble IL-6R. In both cases, association with the signal transducing gp130 receptor is compulsory. However, differences in the downstream signaling mechanisms of IL-6 classic- versus trans-signaling remains largely elusive.
Methods
In this study, we used flow cytometry, quantitative PCR, ELISA and immuno-blotting techniques to investigate IL-6 classic and trans-signaling mechanisms in Human Umbilical Vein Endothelial Cells (HUVECs).
Results
We show that both IL-6R and gp130 are expressed on the surface of human vascular endothelial cells, and that the expression is affected by pro-inflammatory stimuli. In contrast to IL-6 classic signaling, IL-6 trans-signaling induces the release of the pro-inflammatory chemokine Monocyte Chemoattractant Protein-1 (MCP-1) from human vascular endothelial cells. In addition, we reveal that the classic signaling induces activation of the JAK/STAT3 pathway while trans-signaling also activates the PI3K/AKT and the MEK/ERK pathways. Furthermore, we demonstrate that MCP-1 induction by IL-6 trans-signaling requires simultaneous activation of the JAK/STAT3 and PI3K/AKT pathways.
Conclusions
Collectively, our study reports molecular differences in IL-6 classic- and trans-signaling in human vascular endothelial cells; and elucidates the pathways which mediate MCP-1 induction by IL-6 trans-signaling.
Publisher
BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
Subject
1-Phosphatidylinositol 3-kinase
/ Biomedical and Life Sciences
/ Cytokines and Growth Factors
/ Enzyme-linked immunosorbent assay
/ HUVECs
/ Idrott med inriktning mot didaktik
/ Monocyte chemoattractant protein
/ Monocyte chemoattractant Protein-1
/ Physical Education and Sport Pedagogy
/ Proteins
/ Rodents
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