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Int. J. Mol. Sci. 2015, 16(11), 27640-27658; doi:10.3390/ijms161126045

Leptin Promotes cPLA2 Gene Expression through Activation of the MAPK/NF-κB/p300 Cascade

1
Division of Chest Medicine, Shin Kong Wu Ho-Su Memorial Hospital, Taipei 11101, Taiwan
2
Graduate Institute of Basic Medicine, Fu Jen Catholic University, Xinzhuang 24205, Taiwan
3
Department of Internal Medicine, En-Chu-Kong Hospital, Sanxia 23702, Taiwan
4
PhD Program in Nutrition and Food Science, Fu Jen Catholic University, Xinzhuang 24205, Taiwan
*
Author to whom correspondence should be addressed.
Academic Editor: Toshiro Arai
Received: 17 September 2015 / Revised: 26 October 2015 / Accepted: 9 November 2015 / Published: 18 November 2015
(This article belongs to the Special Issue Molecular Research on Obesity and Diabetes)
View Full-Text   |   Download PDF [2858 KB, uploaded 18 November 2015]   |  

Abstract

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 A2-α (cPLA2-α) in vitro in the lung alveolar type II cells, A549, and in vivo in ICR mice. Upregulated cPLA2-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 cPLA2-α mRNA expression. Our data as a whole showed that leptin contributed to lung cPLA2-α expression through OB-R-dependent activation of the MAPKs/NF-κB/p300 cascade. View Full-Text
Keywords: leptin; inflammation; MAPK; NF-κB; p300 leptin; inflammation; MAPK; NF-κB; p300
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Hsu, P.-S.; Wu, C.-S.; Chang, J.-F.; Lin, W.-N. Leptin Promotes cPLA2 Gene Expression through Activation of the MAPK/NF-κB/p300 Cascade. Int. J. Mol. Sci. 2015, 16, 27640-27658.

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