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

International Journal of Molecular Sciences

Pei-Sung Hsu²  Chi-Sheng Wu³  Jia-Feng Chang¹  Wei-Ning Lin³ 

[1] Department of Internal Medicine, En-Chu-Kong Hospital, Sanxia 23702, Taiwan;Division of Chest Medicine, Shin Kong Wu Ho-Su Memorial Hospital, Taipei 11101, Taiwan;Graduate Institute of Basic Medicine, Fu Jen Catholic University, Xinzhuang 24205, Taiwan;

关键词: leptin;    inflammation;    MAPK;    NF-κB;    p300;   

DOI  :  10.3390/ijms161126045

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2015 by the authors; licensee MDPI, Basel, Switzerland.