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Increased expression of placenta growth factor in COPD.

Cheng SL, Wang HC, Yu CJ, Yang PC - Thorax (2008)

Bottom Line: Continuous concomitant treatment with PlGF, TNF-alpha and IL-8 stimulation reduced VEGF expression and induced cell death.This phenomenon was suppressed by VEGF receptor inhibitor (CBO-P11).Concomitant treatment with PlGF, TNF-alpha and IL-8 causes detrimental effects on airway epithelial cells.

View Article: PubMed Central - PubMed

Affiliation: Department of Internal Medicine, National Taiwan University Hospital, No. 7, Chung-Shan South Road, Taipei, Taiwan.

ABSTRACT

Background: Vascular endothelial growth factor (VEGF) and its receptor may have an important role in the pathogenesis of emphysema. The effect of another angiogenic factor, placenta growth factor (PlGF), in chronic obstructive pulmonary disease (COPD) is unknown.

Methods: The serum levels of VEGF and PlGF in patients with COPD (n = 184), smokers (n = 212) and non-smokers (n = 159) and the bronchoalveolar lavage (BAL) fluid levels of VEGF and PlGF in another group (20 patients with COPD, 18 controls) were measured. In vitro cell culture experiments were performed to investigate the effect of PlGF on VEGF.

Results: The mean (SE) serum levels of PlGF were significantly higher in patients with COPD than in controls (27.1 (7.4) pg/ml vs 12.3 (5.1) pg/ml in smokers and 10.8 (6.3) pg/ml in non-smokers, p = 0.005). The levels of PlGF in BAL fluid were also significantly higher in patients with COPD than in controls (45.7 (12.3) pg/ml vs 23.9 (7.6) pg/ml, p = 0.005), associated with an increase in the cytokines tumour necrosis factor-alpha (TNF-alpha) and interleukin-8 (IL-8). In patients with COPD the levels of PlGF correlated inversely with forced expiratory volume in 1 s (FEV(1)) in serum (r = -0.59, p = 0.002) and in BAL fluid (r = -0.51, p = 0.001). While the serum levels of VEGF were the same in patients with COPD and controls, the BAL fluid levels were significantly lower in patients with COPD than in controls (127.5 (30.1) pg/ml vs 237.8 (36.1) pg/ml, p = 0.002). In cultured bronchial epithelial cells, proinflammatory cytokines induced an increase in the protein expression of both PlGF and VEGF. Continuous concomitant treatment with PlGF, TNF-alpha and IL-8 stimulation reduced VEGF expression and induced cell death. This phenomenon was suppressed by VEGF receptor inhibitor (CBO-P11).

Conclusions: The serum and BAL fluid levels of PlGF are increased in patients with COPD and are inversely correlated with FEV(1). Concomitant treatment with PlGF, TNF-alpha and IL-8 causes detrimental effects on airway epithelial cells. These data suggest that bronchial epithelial cells can express PlGF, which may contribute to the pathogenesis of COPD.

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(A) Concentrations of vascular endothelial growth factor (VEGF) and placenta growth factor (PlGF) in bronchoalveolar lavage (BAL) fluid in patients with chronic obstructive pulmonary disease (COPD) and controls (*p = 0.005, **p = 0.002). Error bars are presented as standard errors. (B) Concentrations of cytokines in BAL fluid in patients with COPD and controls. IL-1β, interleukin-1β; TNF-α, tumour necrosis factor-α; TGF-β, transforming growth factor-β; EGF, epidermal growth factor; IL-8, interleukin-8. (*p = 0.003; **p = 0.001; †p = 0.005; ‡p = 0.003; ***p = 0.001). Error bars are presented as standard errors. The coefficients of variation within and between batches were 0.17 and 0.24, respectively. (C) Relationship between PlGF levels in BAL fluid and forced expiratory volume in 1 s (FEV1) percentage predicted in patients with COPD (r = −0.51, p = 0.001). Higher PlGF levels in BAL fluid correlated with worse lung function.
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THX-63-06-0500-f02: (A) Concentrations of vascular endothelial growth factor (VEGF) and placenta growth factor (PlGF) in bronchoalveolar lavage (BAL) fluid in patients with chronic obstructive pulmonary disease (COPD) and controls (*p = 0.005, **p = 0.002). Error bars are presented as standard errors. (B) Concentrations of cytokines in BAL fluid in patients with COPD and controls. IL-1β, interleukin-1β; TNF-α, tumour necrosis factor-α; TGF-β, transforming growth factor-β; EGF, epidermal growth factor; IL-8, interleukin-8. (*p = 0.003; **p = 0.001; †p = 0.005; ‡p = 0.003; ***p = 0.001). Error bars are presented as standard errors. The coefficients of variation within and between batches were 0.17 and 0.24, respectively. (C) Relationship between PlGF levels in BAL fluid and forced expiratory volume in 1 s (FEV1) percentage predicted in patients with COPD (r = −0.51, p = 0.001). Higher PlGF levels in BAL fluid correlated with worse lung function.

Mentions: The characteristics of the 38 subjects (study population 2) receiving bronchoscopic examination and BAL are presented in table 2. The serum levels of PlGF were still significantly higher in patients with COPD (22.4 (9.7) pg/ml than in controls (13.2 (7.8) pg/ml, p<0.05), but the serum concentrations of VEGF were similar in the two groups. The concentrations of VEGF and PlGF in the BAL fluid of patients with COPD and controls are shown in fig 2A. The levels of VEGF were significantly lower in patients with COPD than in normal subjects (COPD 127.5 (30.1) pg/ml vs controls 237.8 (36.1) pg/ml, p = 0.002). However, the concentrations of PlGF in patients with COPD were higher than those of controls (COPD 45.7 (12.3) pg/ml vs controls 23.9 (7.6) pg/ml, p = 0.005; table 2). The levels of proinflammatory cytokines in BAL fluid from patients with COPD (IL-1β: 143.4 (37.9), TNF-α: 205.7 (46.1), TGF-β: 89.5 (35.1), EGF:104.3 (40.7) and IL-8: 216.8 (38.9) pg/ml) were also significantly higher than those from controls (IL-1β: 29.8 (13.6), TNF-α: 30.5 (17.2), TGF-β: 17.4 (8.5), EGF: 21.3 (11.6) and IL-8: 40.2 (18.3) pg/ml; fig 2B). Moreover, higher BAL fluid levels of PlGF were significantly correlated with worse lung function represented by FEV1 (r = −0.51, p = 0.001; fig 2C). The levels of VEGF in BAL fluid did not correlate with FEV1 (r = 0.12, p = 0.51).


Increased expression of placenta growth factor in COPD.

Cheng SL, Wang HC, Yu CJ, Yang PC - Thorax (2008)

(A) Concentrations of vascular endothelial growth factor (VEGF) and placenta growth factor (PlGF) in bronchoalveolar lavage (BAL) fluid in patients with chronic obstructive pulmonary disease (COPD) and controls (*p = 0.005, **p = 0.002). Error bars are presented as standard errors. (B) Concentrations of cytokines in BAL fluid in patients with COPD and controls. IL-1β, interleukin-1β; TNF-α, tumour necrosis factor-α; TGF-β, transforming growth factor-β; EGF, epidermal growth factor; IL-8, interleukin-8. (*p = 0.003; **p = 0.001; †p = 0.005; ‡p = 0.003; ***p = 0.001). Error bars are presented as standard errors. The coefficients of variation within and between batches were 0.17 and 0.24, respectively. (C) Relationship between PlGF levels in BAL fluid and forced expiratory volume in 1 s (FEV1) percentage predicted in patients with COPD (r = −0.51, p = 0.001). Higher PlGF levels in BAL fluid correlated with worse lung function.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2571977&req=5

THX-63-06-0500-f02: (A) Concentrations of vascular endothelial growth factor (VEGF) and placenta growth factor (PlGF) in bronchoalveolar lavage (BAL) fluid in patients with chronic obstructive pulmonary disease (COPD) and controls (*p = 0.005, **p = 0.002). Error bars are presented as standard errors. (B) Concentrations of cytokines in BAL fluid in patients with COPD and controls. IL-1β, interleukin-1β; TNF-α, tumour necrosis factor-α; TGF-β, transforming growth factor-β; EGF, epidermal growth factor; IL-8, interleukin-8. (*p = 0.003; **p = 0.001; †p = 0.005; ‡p = 0.003; ***p = 0.001). Error bars are presented as standard errors. The coefficients of variation within and between batches were 0.17 and 0.24, respectively. (C) Relationship between PlGF levels in BAL fluid and forced expiratory volume in 1 s (FEV1) percentage predicted in patients with COPD (r = −0.51, p = 0.001). Higher PlGF levels in BAL fluid correlated with worse lung function.
Mentions: The characteristics of the 38 subjects (study population 2) receiving bronchoscopic examination and BAL are presented in table 2. The serum levels of PlGF were still significantly higher in patients with COPD (22.4 (9.7) pg/ml than in controls (13.2 (7.8) pg/ml, p<0.05), but the serum concentrations of VEGF were similar in the two groups. The concentrations of VEGF and PlGF in the BAL fluid of patients with COPD and controls are shown in fig 2A. The levels of VEGF were significantly lower in patients with COPD than in normal subjects (COPD 127.5 (30.1) pg/ml vs controls 237.8 (36.1) pg/ml, p = 0.002). However, the concentrations of PlGF in patients with COPD were higher than those of controls (COPD 45.7 (12.3) pg/ml vs controls 23.9 (7.6) pg/ml, p = 0.005; table 2). The levels of proinflammatory cytokines in BAL fluid from patients with COPD (IL-1β: 143.4 (37.9), TNF-α: 205.7 (46.1), TGF-β: 89.5 (35.1), EGF:104.3 (40.7) and IL-8: 216.8 (38.9) pg/ml) were also significantly higher than those from controls (IL-1β: 29.8 (13.6), TNF-α: 30.5 (17.2), TGF-β: 17.4 (8.5), EGF: 21.3 (11.6) and IL-8: 40.2 (18.3) pg/ml; fig 2B). Moreover, higher BAL fluid levels of PlGF were significantly correlated with worse lung function represented by FEV1 (r = −0.51, p = 0.001; fig 2C). The levels of VEGF in BAL fluid did not correlate with FEV1 (r = 0.12, p = 0.51).

Bottom Line: Continuous concomitant treatment with PlGF, TNF-alpha and IL-8 stimulation reduced VEGF expression and induced cell death.This phenomenon was suppressed by VEGF receptor inhibitor (CBO-P11).Concomitant treatment with PlGF, TNF-alpha and IL-8 causes detrimental effects on airway epithelial cells.

View Article: PubMed Central - PubMed

Affiliation: Department of Internal Medicine, National Taiwan University Hospital, No. 7, Chung-Shan South Road, Taipei, Taiwan.

ABSTRACT

Background: Vascular endothelial growth factor (VEGF) and its receptor may have an important role in the pathogenesis of emphysema. The effect of another angiogenic factor, placenta growth factor (PlGF), in chronic obstructive pulmonary disease (COPD) is unknown.

Methods: The serum levels of VEGF and PlGF in patients with COPD (n = 184), smokers (n = 212) and non-smokers (n = 159) and the bronchoalveolar lavage (BAL) fluid levels of VEGF and PlGF in another group (20 patients with COPD, 18 controls) were measured. In vitro cell culture experiments were performed to investigate the effect of PlGF on VEGF.

Results: The mean (SE) serum levels of PlGF were significantly higher in patients with COPD than in controls (27.1 (7.4) pg/ml vs 12.3 (5.1) pg/ml in smokers and 10.8 (6.3) pg/ml in non-smokers, p = 0.005). The levels of PlGF in BAL fluid were also significantly higher in patients with COPD than in controls (45.7 (12.3) pg/ml vs 23.9 (7.6) pg/ml, p = 0.005), associated with an increase in the cytokines tumour necrosis factor-alpha (TNF-alpha) and interleukin-8 (IL-8). In patients with COPD the levels of PlGF correlated inversely with forced expiratory volume in 1 s (FEV(1)) in serum (r = -0.59, p = 0.002) and in BAL fluid (r = -0.51, p = 0.001). While the serum levels of VEGF were the same in patients with COPD and controls, the BAL fluid levels were significantly lower in patients with COPD than in controls (127.5 (30.1) pg/ml vs 237.8 (36.1) pg/ml, p = 0.002). In cultured bronchial epithelial cells, proinflammatory cytokines induced an increase in the protein expression of both PlGF and VEGF. Continuous concomitant treatment with PlGF, TNF-alpha and IL-8 stimulation reduced VEGF expression and induced cell death. This phenomenon was suppressed by VEGF receptor inhibitor (CBO-P11).

Conclusions: The serum and BAL fluid levels of PlGF are increased in patients with COPD and are inversely correlated with FEV(1). Concomitant treatment with PlGF, TNF-alpha and IL-8 causes detrimental effects on airway epithelial cells. These data suggest that bronchial epithelial cells can express PlGF, which may contribute to the pathogenesis of COPD.

Show MeSH
Related in: MedlinePlus