Effects Of Peroxisome Proliferator Activated Receptor-γ On The Inflammation In Chronic Obstructive Pulmonary Disease

Objective To study the effects of peroxisome proliferator activated receptor-γ(PPAR-γ) agonist rosiglitazone and PPAR-y antagonist GW9662 on PPAR-y, nuclear factor-κB (NF-κB) and tumor necrosis factor-a (TNF-a), so as to explore the effects of PPAR-y on the inflammation in chronic obstructive pulmonary disease (COPD).Methods Thirty patients of COPD and 24 healthy controls were included. The peripheral blood mononuclear cells (PBMCs) were isolated from blood of the patients with COPD and healthy controls. The PBMCs with COPD were theated with rosiglitazone and GW9662. The PBMCs were divided into 4 groups:control group (group A), COPD group (group B), COPD rosiglitazone group (group C), COPD rosiglitazone and GW9662 group (group D). The expression of PPAR-y mRNA and NF-κB mRNA was measured with Real-Time PCR. The expression of PPAR-y and NF-κB protein and nuclear translocation were detected using immunofluorescence with laser scanning confocal microscopy. The TNF-a level in cultural supernatant was measured with ELISA.Results (1) The mRNA and protein levels of PPAR-y were lower in group B (0.52±0.10, 55.12±10.38) than that in group A (1,84.66±9.48) (P all< 0.05), while the levels of NF-κB mRNA and protein were higher in group B (1.69±0.07,145.40±17.14) than that in group A (1, 117.55±6.71) (P respectively< 0.01,<0.05). TNF-a level was significantly higher in group B (96.20±1.44)μg/L than that in group A (85.33±1.03)μg/L (P< 0.01). The proteins of PPAR-y and NF-κB were respectively located in cytoplasm and in nucleus in group B, meanwhile the proteins of PPAR-y and NF-κB were located in both cytoplasm and nucleus in group A. (2) After the treatment of rosiglitazone (group C), the mRNA and protein levels of PPAR-y (4.47±0.11, 204.36±11.89) were significantly increased compared with group B (P all< 0.01), while the mRNA and protein levels of NF-κB (0.33±0.04,58.97±13.69) were remarkably decreased compared with group B (P all<0.01).TNF-αlevel (63.04±2.54)μg/L in group C was significantly lower than that in group B (P<0.01). PPAR-γprotein was translocated from cytoplasm into nucleus and NF-κB protein was translocated from nucleus into cytoplasm. (3) Before rosiglitazone treatment with GW9662 pretreated (group D), the mRNA and protein levels of PPAR-γ(2.25±0.31,141.59±23.44) were significantly decreased compared to group C (P all< 0.01), but higher compared with group B and group A (P all< 0.01). The mRNA and protein levels of NF-κB (0.64±0.02,90.06±9.65) were increased compared with group C (P respectively < 0.01,< 0.05), but decreased compared to group B and group A (P< 0.01 or< 0.05). TNF-a level in group D (82.27±1.85)μg/L was significantly increased than that in group C (P< 0.01), but decreased as compared to group B (P< 0.01). PPAR-γprotein translocated from nucleus into cytoplasm and NF-κB protein partly translocated from cytoplasm into nucleus. (4) The negative correlations were respectively existed between PPAR-γprotein and NF-κB protein, TNF-αlevel (P all< 0.01). The NF-κB protein was positively correlated to TNF-αlevel (P< 0.01).Conclusion The expression and activity of PPAR-γwere decreased in COPD patients. PPAR-γagonist, rosiglitazone, could alleviate the inflammation in COPD through upregulating the expression of PPAR-γand promoting nuclear translocation and inhibition of NF-κB and TNF-α. It was complicated that PPAR-γmaybe play an important role in the inflammation of COPD.