Leptin increases TNF-α expression and production through phospholipase D1 in Raw 264.7 cells

Epidemiological evidence suggests that obesity is associated with inflammation of the respiratory tract and the pathogenesis of asthma. The purpose of this study was to examine the role of phospholipase D1 (PLD1) in leptin-induced expression of the proinflammatory cytokine, tumor necrosis factor (TN...

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Published in:PloS one 2014-07, Vol.9 (7), p.e102373-e102373
Main Authors: Lee, Se-Min, Choi, Hye-Jin, Oh, Cheong-Hae, Oh, Jae-Won, Han, Joong-Soo
Format: Article
Language:English
Subjects:
Acids
Activation
Animals
Apoptosis
Asthma
Biochemistry
Biology and Life Sciences
Biomedical research
Cell Line
Cytokines
Enzyme inhibitors
Epidemiology
Gene expression
Inflammation
Inhibition
Inhibitors
JNK protein
Kinases
Leptin
Leptin - immunology
Macrophages - immunology
Medicine
Medicine and Health Sciences
Mice
Molecular biology
Obesity
Pathogenesis
Pediatrics
Penicillin
Phospholipase
Phospholipase D - immunology
Phospholipase D1
Phosphorylation
Proteins
Research and Analysis Methods
Respiratory tract
Rodents
Signal Transduction
siRNA
Tumor Necrosis Factor-alpha - genetics
Tumor Necrosis Factor-alpha - immunology
Tumor necrosis factor-α
Up-Regulation
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creator Lee, Se-Min
Choi, Hye-Jin
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description Epidemiological evidence suggests that obesity is associated with inflammation of the respiratory tract and the pathogenesis of asthma. The purpose of this study was to examine the role of phospholipase D1 (PLD1) in leptin-induced expression of the proinflammatory cytokine, tumor necrosis factor (TNF)-α, and to suggest a molecular link between obesity and respiratory tract inflammation. We investigated whether leptin, a typical adipocytokine, plays a role in the expression of TNF-α through increased PLD1 activity in Raw 264.7. Leptin enhanced the activity of PLD1 through activation of PLCγ and Src, while PLD1 siRNA decreased the leptin-induced expression and production of TNF-α. Leptin-induced PLD activation was also inhibited by a PLCγ inhibitor (PAO) and Src kinase inhibitor (PP2), indicating that PLCγ and Src kinase are upstream activators of PLD1. Down-regulation of PLD1 also completely blocked activation of p70S6K, an activator of JNK. Leptin-induced expression of TNF-α was also prevented by inhibition of p70S6K and JNK. Taken together, these results indicate that PLD1 acts as an important regulator of leptin-induced expression of TNF-α by participating in the PLCγ/Src/PLD1/PA/p70S6K/JNK pathway.
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The purpose of this study was to examine the role of phospholipase D1 (PLD1) in leptin-induced expression of the proinflammatory cytokine, tumor necrosis factor (TNF)-α, and to suggest a molecular link between obesity and respiratory tract inflammation. We investigated whether leptin, a typical adipocytokine, plays a role in the expression of TNF-α through increased PLD1 activity in Raw 264.7. Leptin enhanced the activity of PLD1 through activation of PLCγ and Src, while PLD1 siRNA decreased the leptin-induced expression and production of TNF-α. Leptin-induced PLD activation was also inhibited by a PLCγ inhibitor (PAO) and Src kinase inhibitor (PP2), indicating that PLCγ and Src kinase are upstream activators of PLD1. Down-regulation of PLD1 also completely blocked activation of p70S6K, an activator of JNK. Leptin-induced expression of TNF-α was also prevented by inhibition of p70S6K and JNK. 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subjects Acids
Activation
Animals
Apoptosis
Asthma
Biochemistry
Biology and Life Sciences
Biomedical research
Cell Line
Cytokines
Enzyme inhibitors
Epidemiology
Gene expression
Inflammation
Inhibition
Inhibitors
JNK protein
Kinases
Leptin
Leptin - immunology
Macrophages - immunology
Medicine
Medicine and Health Sciences
Mice
Molecular biology
Obesity
Pathogenesis
Pediatrics
Penicillin
Phospholipase
Phospholipase D - immunology
Phospholipase D1
Phosphorylation
Proteins
Research and Analysis Methods
Respiratory tract
Rodents
Signal Transduction
siRNA
Tumor Necrosis Factor-alpha - genetics
Tumor Necrosis Factor-alpha - immunology
Tumor necrosis factor-α
Up-Regulation
title Leptin increases TNF-α expression and production through phospholipase D1 in Raw 264.7 cells
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