Leptin Promotes cPLA2 Gene Expression through Activation of the MAPK/NF-κB/p300 Cascade
AbstractHyperplasia 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
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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.
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. International Journal of Molecular Sciences. 2015; 16(11):27640-27658.Chicago/Turabian Style
Hsu, Pei-Sung; Wu, Chi-Sheng; Chang, Jia-Feng; Lin, Wei-Ning. 2015. "Leptin Promotes cPLA2 Gene Expression through Activation of the MAPK/NF-κB/p300 Cascade." Int. J. Mol. Sci. 16, no. 11: 27640-27658.