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Leptin Promotes cPLA(2) Gene Expression through Activation of the MAPK/NF-κB/p300 Cascade

Hyperplasia or hypertrophy of adipose tissues plays a crucial role in obesity, which is accompanied by the release of leptin. Recently, obesity was determined to be associated with various pulmonary diseases including asthma, acute lung injury, and chronic obstructive pulmonary disease. However, how...

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Autores principales: Hsu, Pei-Sung, Wu, Chi-Sheng, Chang, Jia-Feng, Lin, Wei-Ning
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4661903/
https://www.ncbi.nlm.nih.gov/pubmed/26593914
http://dx.doi.org/10.3390/ijms161126045
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author Hsu, Pei-Sung
Wu, Chi-Sheng
Chang, Jia-Feng
Lin, Wei-Ning
author_facet Hsu, Pei-Sung
Wu, Chi-Sheng
Chang, Jia-Feng
Lin, Wei-Ning
author_sort Hsu, Pei-Sung
collection PubMed
description Hyperplasia or hypertrophy of adipose tissues plays a crucial role in obesity, which is accompanied by the release of leptin. Recently, obesity was determined to be associated with various pulmonary diseases including asthma, acute lung injury, and chronic obstructive pulmonary disease. However, how obesity contributes to pulmonary diseases and whether leptin directly regulates lung inflammation remains unclear. We used cell and animal models to study the mechanisms of leptin mediation of pulmonary inflammation. We found that leptin activated de novo synthesis of cytosolic phospholipase A(2)-α (cPLA(2)-α) in vitro in the lung alveolar type II cells, A549, and in vivo in ICR mice. Upregulated cPLA(2)-α protein was attenuated by pretreatment with an OB-R blocking antibody, U0126, SB202190, SP600125, Bay11-7086, garcinol, and p300 siRNA, suggesting roles of p42/p44 MAPK, p38 MAPK, JNK1/2, NF-κB, and p300 in leptin effects. Leptin enhanced the activities of p42/p44 MAPK, p38 MAPK, JNK1/2, and p65 NF-κB in a time-dependent manner. Additional studies have suggested the participation of OB-R, p42/p44 MAPK, and JNK1/2 in leptin-increased p65 phosphorylation. Furthermore, p300 phosphorylation and histone H4 acetylation were reduced by blockage of OB-R, p42/p44 MAPK, p38 MAPK, JNK1/2, and NF-κB in leptin-stimulated cells. Similarly, blockage of the MAPKs/NF-κB/p300 cascade significantly inhibited leptin-mediated cPLA(2)-α mRNA expression. Our data as a whole showed that leptin contributed to lung cPLA(2)-α expression through OB-R-dependent activation of the MAPKs/NF-κB/p300 cascade.
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spelling pubmed-46619032015-12-10 Leptin Promotes cPLA(2) Gene Expression through Activation of the MAPK/NF-κB/p300 Cascade Hsu, Pei-Sung Wu, Chi-Sheng Chang, Jia-Feng Lin, Wei-Ning Int J Mol Sci Article Hyperplasia or hypertrophy of adipose tissues plays a crucial role in obesity, which is accompanied by the release of leptin. Recently, obesity was determined to be associated with various pulmonary diseases including asthma, acute lung injury, and chronic obstructive pulmonary disease. However, how obesity contributes to pulmonary diseases and whether leptin directly regulates lung inflammation remains unclear. We used cell and animal models to study the mechanisms of leptin mediation of pulmonary inflammation. We found that leptin activated de novo synthesis of cytosolic phospholipase A(2)-α (cPLA(2)-α) in vitro in the lung alveolar type II cells, A549, and in vivo in ICR mice. Upregulated cPLA(2)-α protein was attenuated by pretreatment with an OB-R blocking antibody, U0126, SB202190, SP600125, Bay11-7086, garcinol, and p300 siRNA, suggesting roles of p42/p44 MAPK, p38 MAPK, JNK1/2, NF-κB, and p300 in leptin effects. Leptin enhanced the activities of p42/p44 MAPK, p38 MAPK, JNK1/2, and p65 NF-κB in a time-dependent manner. Additional studies have suggested the participation of OB-R, p42/p44 MAPK, and JNK1/2 in leptin-increased p65 phosphorylation. Furthermore, p300 phosphorylation and histone H4 acetylation were reduced by blockage of OB-R, p42/p44 MAPK, p38 MAPK, JNK1/2, and NF-κB in leptin-stimulated cells. Similarly, blockage of the MAPKs/NF-κB/p300 cascade significantly inhibited leptin-mediated cPLA(2)-α mRNA expression. Our data as a whole showed that leptin contributed to lung cPLA(2)-α expression through OB-R-dependent activation of the MAPKs/NF-κB/p300 cascade. MDPI 2015-11-18 /pmc/articles/PMC4661903/ /pubmed/26593914 http://dx.doi.org/10.3390/ijms161126045 Text en © 2015 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons by Attribution (CC-BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Hsu, Pei-Sung
Wu, Chi-Sheng
Chang, Jia-Feng
Lin, Wei-Ning
Leptin Promotes cPLA(2) Gene Expression through Activation of the MAPK/NF-κB/p300 Cascade
title Leptin Promotes cPLA(2) Gene Expression through Activation of the MAPK/NF-κB/p300 Cascade
title_full Leptin Promotes cPLA(2) Gene Expression through Activation of the MAPK/NF-κB/p300 Cascade
title_fullStr Leptin Promotes cPLA(2) Gene Expression through Activation of the MAPK/NF-κB/p300 Cascade
title_full_unstemmed Leptin Promotes cPLA(2) Gene Expression through Activation of the MAPK/NF-κB/p300 Cascade
title_short Leptin Promotes cPLA(2) Gene Expression through Activation of the MAPK/NF-κB/p300 Cascade
title_sort leptin promotes cpla(2) gene expression through activation of the mapk/nf-κb/p300 cascade
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4661903/
https://www.ncbi.nlm.nih.gov/pubmed/26593914
http://dx.doi.org/10.3390/ijms161126045
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