Online citations, reference lists, and bibliographies.
Please confirm you are human
(Sign Up for free to never see this)
← Back to Search

Leptin Increases TNF-α Expression And Production Through Phospholipase D1 In Raw 264.7 Cells

Se-Min Lee, Hye-jin Choi, C. Oh, Jae-won Oh, J. Han
Published 2014 · Biology, Medicine

Save to my Library
Download PDF
Analyze on Scholarcy
Share
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.
This paper references
10.1074/JBC.M301364200
Activation of the p70 S6 Kinase and Phosphorylation of the 4E-BP1 Repressor of mRNA Translation by Type I Interferons*
F. Lekmine (2003)
10.1042/BJ2690281
The regulation and cellular functions of phosphatidylcholine hydrolysis.
M. Billah (1990)
10.1016/j.cub.2003.11.021
PLD1 Regulates mTOR Signaling and Mediates Cdc42 Activation of S6K1
Y. Fang (2003)
10.1152/japplphysiol.00749.2009
Obesity, airway hyperresponsiveness, and inflammation.
S. Shore (2010)
10.1016/j.molimm.2008.06.007
Bradykinin-induced IL-6 expression through bradykinin B2 receptor, phospholipase C, protein kinase Cdelta and NF-kappaB pathway in human synovial fibroblasts.
C. Lee (2008)
10.1046/j.1600-6143.2004.00716.x
Inhibition of p38 Pathway Suppresses Human Islet Production of Pro‐Inflammatory Cytokines and Improves Islet Graft Function
T. Matsuda (2005)
10.5051/jpis.2010.40.3.119
Leptin potentiates Prevotella intermedia lipopolysaccharide-induced production of TNF-α in monocyte-derived macrophages
S. Kim (2010)
10.1172/JCI117899
The expression of tumor necrosis factor in human adipose tissue. Regulation by obesity, weight loss, and relationship to lipoprotein lipase.
P. Kern (1995)
10.1126/SCIENCE.281.5383.1683
Biological action of leptin as an angiogenic factor.
M. Sierra-Honigmann (1998)
10.1182/BLOOD-2006-08-042192
mTOR-dependent synthesis of Bcl-3 controls the retraction of fibrin clots by activated human platelets.
A. Weyrich (2007)
Bradykinininduced IL-6 expression through bradykinin B2 receptor, phospholipase C, protein kinase Cdelta and NF-kappaB pathway in human synovial fibroblasts
CH Lee (2008)
10.1016/S0092-8674(01)00240-9
Obesity and the Regulation of Energy Balance
B. Spiegelman (2001)
10.4049/jimmunol.1300466
SHP-1–Pyk2–Src Protein Complex and p38 MAPK Pathways Independently Regulate IL-10 Production in Lipopolysaccharide-Stimulated Macrophages
C. Okenwa (2013)
Central nervous system control of food intake and body
GJ Morton (2006)
10.1016/j.cyto.2008.07.006
Inhibition of lipopolysaccharide-induced nitric oxide synthesis by nicotine through S6K1-p42/44 MAPK pathway and STAT3 (Ser 727) phosphorylation in Raw 264.7 cells.
Shin-Young Park (2008)
10.1016/j.molcel.2010.09.026
Regulation of the mTOR complex 1 pathway by nutrients, growth factors, and stress.
S. Sengupta (2010)
10.1016/S1388-1981(99)00097-9
Phospholipase D and membrane traffic. Potential roles in regulated exocytosis, membrane delivery and vesicle budding.
D. Jones (1999)
10.4049/jimmunol.180.8.5636
The Tyrosine Kinase Pyk2 Mediates Lipopolysaccharide-Induced IL-8 Expression in Human Endothelial Cells1
A. Anand (2008)
10.1152/AJPHEART.2000.278.5.H1537
Fluid flow activates a regulator of translation, p70/p85 S6 kinase, in human endothelial cells.
L. Kraiss (2000)
10.4049/jimmunol.174.11.6820
Leptin Promotes Differentiation and Survival of Human Dendritic Cells and Licenses Them for Th1 Priming 1
B. Mattioli (2005)
Leptin enhances TNF-alpha production via p38 and JNK MAPK in LPS-stimulated Kupffer cells.
J. Shen (2005)
10.1111/j.1476-5381.2009.00022.x
Inhibition of inducible NO synthase, cyclooxygenase‐2 and interleukin‐1β by torilin is mediated by mitogen‐activated protein kinases in microglial BV2 cells
Y. Choi (2009)
10.1074/jbc.M007383200
Leptin Induces Mitochondrial Superoxide Production and Monocyte Chemoattractant Protein-1 Expression in Aortic Endothelial Cells by Increasing Fatty Acid Oxidation via Protein Kinase A*
S. Yamagishi (2001)
10.1002/jcb.21166
Phospholipase D1 activation through Src and Ras is involved in basic fibroblast growth factor‐induced neurite outgrowth of H19‐7 cells
Doo-Yi Oh (2007)
10.1128/MCB.00199-07
Activation of the c-Jun N-Terminal Kinase Pathway by MST1 Is Essential and Sufficient for the Induction of Chromatin Condensation during Apoptosis
S. Ura (2007)
10.1006/CLIN.1995.1052
Augmented Production of Tumor Necrosis Factor-α in Obese Mice
T. Yamakawa (1995)
10.1074/jbc.M109.010017
House Dust Mite Allergen Der f 2-induced Phospholipase D1 Activation Is Critical for the Production of Interleukin-13 through Activating Transcription Factor-2 Activation in Human Bronchial Epithelial Cells*
Shin-Young Park (2009)
10.1074/jbc.M708568200
Regulation of Interleukin-6-induced Hepatic Insulin Resistance by Mammalian Target of Rapamycin through the STAT3-SOCS3 Pathway*
J. Kim (2008)
10.1096/FASEBJ.12.1.57
Leptin regulates proinflammatory immune responses.
S. Loffreda (1998)
10.1158/0008-5472.CAN-10-4158
Transcriptional control of cellular metabolism by mTOR signaling.
J. Yecies (2011)
10.1016/j.molimm.2008.11.003
Involvement of intracellular signaling cascades in inflammatory responses in human intestinal epithelial cells following Vibrio cholerae infection.
A. Bandyopadhaya (2009)
10.1146/ANNUREV.PA.36.040196.002405
Regulation of phosphoinositide phospholipases by hormones, neurotransmitters, and other agonists linked to G proteins.
J. Exton (1996)
10.1016/J.INTIMP.2004.04.001
Up-regulation of phospholipase Cgamma1 and phospholipase D during the differentiation of human monocytes to dendritic cells.
Hyun Kyu Kang (2004)
10.1152/AJPLUNG.00010.2004
Leptin augments alveolar macrophage leukotriene synthesis by increasing phospholipase activity and enhancing group IVC iPLA2 (cPLA2gamma) protein expression.
P. Mancuso (2004)
10.1016/J.YEXCR.2003.12.021
Interferon-gamma engages the p70 S6 kinase to regulate phosphorylation of the 40S S6 ribosomal protein.
F. Lekmine (2004)
10.1016/j.molimm.2010.06.006
Molecular mechanism underlying the inflammatory complication of leptin in macrophages.
Tamisha Vaughan (2010)
10.1016/S0009-3084(99)00027-4
Possible role of phospholipase D in cellular differentiation and apoptosis.
S. Nakashima (1999)
10.1038/nature05026
Central nervous system control of food intake and body weight
G. Morton (2006)
10.1002/jnr.21602
A novel role of hippocalcin in bFGF‐induced neurite outgrowth of H19‐7 cells
Doo-Yi Oh (2008)
10.1210/ENDO.142.11.8484
Leptin stimulates catecholamine synthesis in a PKC-dependent manner in cultured porcine adrenal medullary chromaffin cells.
K. Takekoshi (2001)
10.1146/ANNUREV.BIOCHEM.68.1.913
eIF4 initiation factors: effectors of mRNA recruitment to ribosomes and regulators of translation.
A. Gingras (1999)
10.4049/jimmunol.164.4.2028
Lipopolysaccharide Induces Actin Reorganization and Tyrosine Phosphorylation of Pyk2 and Paxillin in Monocytes and Macrophages1
L. Williams (2000)
Augmented production of tumor necrosis factor-alpha in obese mice.
T. Yamakawa (1995)
10.1016/j.cellsig.2008.06.008
Lysophosphatidic acid upregulates vascular endothelial growth factor-C and tube formation in human endothelial cells through LPA(1/3), COX-2, and NF-kappaB activation- and EGFR transactivation-dependent mechanisms.
Chi-Iou Lin (2008)
10.1139/O59-099
A rapid method of total lipid extraction and purification.
E. Bligh (1959)
10.1046/j.1365-2249.2003.02190.x
Role of leptin as an immunomodulator of blood mononuclear cells: mechanisms of action
V. Sánchez-Margalet (2003)
10.1242/jcs.02564
Phosphatidylinositol (3,4,5)-trisphosphate specifically interacts with the phox homology domain of phospholipase D1 and stimulates its activity
J. Lee (2005)
10.1172/JCI119532
Receptor-mediated regional sympathetic nerve activation by leptin.
W. Haynes (1997)
10.1038/sj.bjp.0706856
The effects of cardamonin on lipopolysaccharide‐induced inflammatory protein production and MAP kinase and NFκB signalling pathways in monocytes/macrophages
S. Hatziieremia (2006)
10.1016/J.JACI.2004.10.007
Effect of leptin on allergic airway responses in mice.
S. Shore (2005)
10.1074/jbc.M706706200
Leptin Induces Macrophage Lipid Body Formation by a Phosphatidylinositol 3-Kinase- and Mammalian Target of Rapamycin-dependent Mechanism*
C. Maya-Monteiro (2008)
10.1038/27376
Leptin and the regulation of body weight in mammals
J. Friedman (1998)
10.1046/j.1471-4159.2003.01562.x
Effects of phosphatidylserine on p38 mitogen activated protein kinase, cyclic AMP responding element binding protein and nuclear factor‐κB activation in resting and activated microglial cells
M. A. Ajmone-Cat (2003)
10.1016/J.LFS.2005.04.004
Leptin enhances TNF-α production via p38 and JNK MAPK in LPS-stimulated Kupffer cells
J. Shen (2005)



This paper is referenced by
10.3390/ijms21114153
The Impact of Photoperiod on the Leptin Sensitivity and Course of Inflammation in the Anterior Pituitary
M. Wójcik (2020)
Estratégias para as opções dietéticas de combate à obesidade relacionadas com a morbilidade cardiometabolica
Paulo Bispo (2017)
10.4161/21623945.2014.985020
Role of amyloid β in the induction of lipolysis and secretion of adipokines from human adipose tissue
Zhongxiao Wan (2015)
10.1016/j.freeradbiomed.2018.12.029
The triangle of death of neurons: Oxidative damage, mitochondrial dysfunction, and loss of choline-containing biomolecules in brains of mice treated with doxorubicin. Advanced insights into mechanisms of chemotherapy induced cognitive impairment ("chemobrain") involving TNF-α.
X. Ren (2019)
10.5772/INTECHOPEN.74327
The Asthma Obese Phenotype
M. Otelea (2018)
10.1016/j.jpain.2019.02.097
Regular Swimming Exercise Attenuated Neuroma Pain in Rats: Involvement of Leptin and Adiponectin.
Lingling Sun (2019)
10.1155/2020/7974537
Leptin Receptor Deficiency Protects Mice against Chronic Cerebral Hypoperfusion-Induced Neuroinflammation and White Matter Lesions
Y. Du (2020)
10.1016/j.jaci.2017.04.016
CDC42‐related genes are upregulated in helper T cells from obese asthmatic children
D. Rastogi (2018)
10.1155/2019/7129476
The Influence of Photoperiod on the Action of Exogenous Leptin on Gene Expression of Proinflammatory Cytokines and Their Receptors in the Thoracic Perivascular Adipose Tissue (PVAT) in Ewes
A. Krawczyńska (2019)
THE EFFECT OF PROPHYLACTIC INHIBITION OF INDUCIBLE NITRIC OXIDE SYNTHASE BY AMINOGUANIDINEON SERUM LEVELS OF SOME ADIPOCYTOKINES IN PRISTANE-INDUCED ARTHRITISIN RATS
S. H. Ali (2015)
10.1016/j.metabol.2014.10.017
Leptin in health and disease: facts and expectations at its twentieth anniversary.
S. Polyzos (2015)
10.1016/j.cellimm.2015.08.003
PLD1 activation mediates Amb a 1-induced Th2-associated cytokine expression via the JNK/ATF-2 pathway in BEAS-2B cells.
Joo-Hwa Kim (2015)
10.1038/s41366-018-0005-5
Targeted disruption of the iNOS gene improves adipose tissue inflammation and fibrosis in leptin-deficient ob/ob mice: role of tenascin C
S. Becerril (2018)
10.22358/JAFS/110022/2019
Photoperiodic conditions as a factor modulating leptin influenceon pro-inflammatory cytokinesand their receptors gene expression in ewe’s aorta
A. Krawczyńska (2019)
10.1152/ajpregu.00262.2014
Overnutrition, mTOR signaling, and cardiovascular diseases.
G. Jia (2014)
10.3389/fimmu.2018.00111
Leptin Mediates In Vivo Neutrophil Migration: Involvement of Tumor Necrosis Factor-Alpha and CXCL1
Glaucia Souza-Almeida (2018)
10.7730/JSCM.2016.28.2.147
A Study of the Effect on Obesity in Taeeumin Animal-experimental Model Induced Lung Fibrosis with Bleomycin
Yoonha Kim (2016)
10.1002/JLB.MR1218-478R
Leptin in the regulation of the immunometabolism of adipose tissue‐macrophages
L. Monteiro (2019)
10.1016/j.alit.2017.06.002
Obesity-related systemic oxidative stress: An important factor of poor asthma control.
Masako To (2018)
Semantic Scholar Logo Some data provided by SemanticScholar