Korean J Pediatr.  2013 Apr;56(4):151-158. 10.3345/kjp.2013.56.4.151.

Expression of peroxisome proliferator-activated receptor (PPAR)-alpha and PPAR-gamma in the lung tissue of obese mice and the effect of rosiglitazone on proinflammatory cytokine expressions in the lung tissue

• Ryu SL
• Shim JW
• Kim DS
• Jung HL
• Park MS
• Park SH
• Lee J
• Lee WY
• Shim JY

• KMID: 1427931
• DOI: http://doi.org/10.3345/kjp.2013.56.4.151

Abstract

PURPOSE
We investigated the mRNA levels of peroxisome proliferator-activated receptor (PPAR)-alpha, PPAR-gamma, adipokines, and cytokines in the lung tissue of lean and obese mice with and without ovalbumin (OVA) challenge, and the effect of rosiglitazone, a PPAR-gamma agonist.
METHODS
We developed 6 mice models: OVA-challenged lean mice with and without rosiglitazone; obese mice with and without rosiglitazone; and OVA-challenged obese mice with and without rosiglitazone. We performed real-time polymerase chain reaction for leptin, leptin receptor, adiponectin, vascular endothelial growth factor (VEGF), tumor necrosis factor (TNF)-alpha, transforming growth factor (TGF)-beta, PPAR-alpha and PPAR-gamma from the lung tissue and determined the cell counts and cytokine levels in the bronchoalveolar lavage fluid.
RESULTS
Mice with OVA challenge showed airway hyperresponsiveness. The lung mRNA levels of PPARalpha and PPAR-gamma increased significantly in obese mice with OVA challenge compared to that in other types of mice and decreased after rosiglitazone administeration. Leptin and leptin receptor expression increased in obese mice with and without OVA challenge and decreased following rosiglitazone treatment. Adiponectin mRNA level increased in lean mice with OVA challenge. Lung VEGF, TNF-alpha, and TGF-beta mRNA levels increased in obese mice with and without OVA challenge compared to that in the control mice. However, rosiglitazone reduced only TGF-beta expression in obese mice, and even augmented VEGF expression in all types of mice. Rosiglitazone treatment did not reduce airway responsiveness, but increased neutrophils and macrophages in the bronchoalveolar lavage fluid.
CONCLUSION
PPAR-alpha and PPAR-gamma expressions were upregulated in the lung tissue of OVA-challenged obese mice however, rosiglitazone treatment did not downregulate airway inflammation in these mice.

Keyword

Peroxisome proliferator-activated receptors; Obesity; Transforming growth factor-beta; Vascularendothelial growth factor; Tumor necrosis factor-alpha

MeSH Terms

Adipokines
Adiponectin
Animals
Bronchoalveolar Lavage
Cell Count
Cytokines
Inflammation
Leptin
Lung
Macrophages
Mice
Mice, Obese
Neutrophils
Obesity
Ovalbumin
Ovum
Peroxisome Proliferator-Activated Receptors
Peroxisomes
PPAR alpha
Real-Time Polymerase Chain Reaction
Receptors, Leptin
RNA, Messenger
Thiazolidinediones
Transforming Growth Factor beta
Transforming Growth Factors
Tumor Necrosis Factor-alpha
Vascular Endothelial Growth Factor A
Adipokines
Adiponectin
Cytokines
Leptin
Ovalbumin
PPAR alpha
Peroxisome Proliferator-Activated Receptors
RNA, Messenger
Receptors, Leptin
Thiazolidinediones
Transforming Growth Factor beta
Transforming Growth Factors
Tumor Necrosis Factor-alpha
Vascular Endothelial Growth Factor A