JOURNAL ARTICLE

[Effects of rosiglitazone on peroxisome proliferator activated receptor-γ pathway in patients with chronic obstructive pulmonary disease]

Xiao-li Zeng, Xiao-ju Liu, Hai-rong Bao, Yi Zhang, En-li Tan, Jian-Min Liao
Chinese Journal of Tuberculosis and Respiratory Diseases 2011, 34 (10): 743-8
22321707

OBJECTIVE: To explore the effects of rosiglitazone on peroxisome proliferator activated receptor-γ (PPAR-γ), nuclear factor-κB and tumor necrosis factor-α (TNF-α) in patients with chronic obstructive pulmonary disease (COPD).

METHODS: From Apr. 2010 to Nov. 2010, 30 patients with acute exacerbations of COPD, 22 males and 8 females, age 54 - 87 (mean 72 ± 9) years and 24 healthy controls, 18 males and 6 females, age 52 - 80 (mean 69 ± 10) years were included. The peripheral blood mononuclear cells (PBMCs) were isolated from venous blood and then cultured. On the basis of the treatment given, the PBMCs of COPD patients were divided into 3 groups: non-treatment group, rosiglitazone treatment group (rosiglitazone group) and rosiglitazone and GW9662 treatment group (combined treatment group). Cells from the healthy controls (control group) did not receive any drug treatment. The mRNA expression of PPAR-γ and NF-κB was measured with real-time PCR. The protein expression and nuclear translocation of PPAR-γ and NF-κB were detected using immunofluorescence with laser scanning confocal microscopy. The TNF-α level in culture supernatant was measured with ELISA. One-way ANOVA and LSD-t test and the Pearson correlation coefficient were used for statistical analysis.

RESULTS: The mRNA and protein levels of PPAR-γ were lower in the non-treatment group (0.52 ± 0.10, 55 ± 11) than those in the control group (1, 85 ± 9), while the levels of NF-κB mRNA and protein were higher in the non-treatment group (1.69 ± 0.07, 145 ± 17) than those in the control group (1, 118 ± 7). The mRNA and protein levels of PPAR-γ in the rosiglitazone group (4.47 ± 0.11, 204 ± 12) were significantly increased compared with the non-treatment group, while the mRNA and protein levels of NF-κB (0.33 ± 0.04, 59 ± 14) were remarkably decreased compared with the non-treatment group. The mRNA and protein levels of PPAR-γ (2.25 ± 0.31, 142 ± 23) were significantly decreased in the combined treatment group compared to the rosiglitazone group, but higher compared with the non-treatment group, while the mRNA and protein levels of NF-κB (0.64 ± 0.02, 90 ± 10) were increased compared with the rosiglitazone group, but decreased compared to the non-treatment group (F = 29.21 - 567.42, all P < 0.01). The TNF-α level was significantly higher in the non-treatment group (96.2 ± 1.4) µg/L than that in the control group (85.3 ± 1.0) µg/L. The TNF-α level in the rosiglitazone group (63.0 ± 2.5) µg/L was remarkably decreased compared with the non-treatment group, while that in the combined treatment group (83.3 ± 1.9) µg/L was increased compared with the rosiglitazone group, but decreased compared to the non-treatment group (F = 293.72, P < 0.01). The proteins of PPAR-γ and NF-κB were respectively located in cytoplasm and in nucleus in the non-treatment group, meanwhile they were located in both cytoplasm and nucleus in the control group. PPAR-γ protein was translocated from cytoplasm into nucleus and NF-κB protein was translocated from nucleus into cytoplasm in the rosiglitazone group. In the combined treatment group, PPAR-γ protein translocated from nucleus into cytoplasm and NF-κB protein partly translocated from cytoplasm into nucleus. By linear correlation analysis, PPAR-γ protein was negatively correlated with NF-κB protein and TNF-α level (r = -0.935, -0.924, all P < 0.01), while NF-κB protein was positively correlated to TNF-α level (r = 0.846, P < 0.01).

CONCLUSIONS: The expression and activity of PPAR-γ were decreased in COPD patients. PPAR-γ agonist rosiglitazone inhibited inflammation in COPD through upregulating the expression and activity of PPAR-γ and inhibition of NF-κB and TNF-α. It suggests that PPAR-γ may play an important role in the inflammation of COPD.

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