Comparing the effects of fluticasone, anti-IgE and anti-TNF treatments in a chronic asthma model

BACKGROUND: Corticosteroids are used in the treatment of asthma. The aim of this study was to determine the efficacy of anti-IgE and anti-TNF alpha as asthma treatments. METHODS: A mouse model of chronic asthma was developed. The fluticasone group was exposed to fluticasone and the anti-IgE and anti-TNF groups were administered anti-IgE or anti-TNF. IL-4, and IgE levels were measured, and histological analysis, pathological analysis and miRNA-126, miRNA-133a analyses were applied. RESULTS: The cell concentration in the BAL fluid decreased in all the treatment groups. The rate of perivascular and peribronchial cell infiltration decreased in the lung in the high-dose anti-IgE and anti-TNF groups. Smooth muscle thickness decreased in the lung tissue in the low-dose anti-IgE and anti-TNF groups. Bronchial wall thickness decreased in the lung tissue in the fluticasone+anti-IgE group. The IL-4 level in BAL fluid decreased in the high-dose anti-IgE, fluticasone+anti-IgE and anti-TNF groups. IgE levels increased in the BAL fluid in the high-dose anti-IgE and anti-TNF groups. The lymphocyte level increased in the BAL fluid in the high-dose anti-IgE group. The macrophage level decreased in the BAL fluid in the anti-TNF group. The relative expression of miRNA-126 increased in all groups. The relative expression of miRNA-133a decreased in the placebo and fluticasone groups. The relative expression of miRNA-133a increased in the low-dose anti-IgE, high-dose anti-IgE, fluticasone+anti-IgE and anti-TNF groups. CONCLUSIONS: The results showed that anti-IgE is successful as a treatment. Fluticasone+anti-IgE and anti-TNF were seen to be superior to other therapeutic modalities when used for prophylaxis

No disponible

Comparing the effects of fluticasone, anti-IgE and anti-TNF treatments in a chronic asthma model.

BACKGROUND: Corticosteroids are used in the treatment of asthma. The aim of this study was to determine the efficacy of anti-IgE and anti-TNF alpha as asthma treatments. METHODS: A mouse model of chronic asthma was developed. The fluticasone group was exposed to fluticasone and the anti-IgE and anti-TNF groups were administered anti-IgE or anti-TNF. IL-4, and IgE levels were measured, and histological analysis, pathological analysis and miRNA-126, miRNA-133a analyses were applied. RESULTS: The cell concentration in the BAL fluid decreased in all the treatment groups. The rate of perivascular and peribronchial cell infiltration decreased in the lung in the high-dose anti-IgE and anti-TNF groups. Smooth muscle thickness decreased in the lung tissue in the low-dose anti-IgE and anti-TNF groups. Bronchial wall thickness decreased in the lung tissue in the fluticasone+anti-IgE group. The IL-4 level in BAL fluid decreased in the high-dose anti-IgE, fluticasone+anti-IgE and anti-TNF groups. IgE levels increased in the BAL fluid in the high-dose anti-IgE and anti-TNF groups. The lymphocyte level increased in the BAL fluid in the high-dose anti-IgE group. The macrophage level decreased in the BAL fluid in the anti-TNF group. The relative expression of miRNA-126 increased in all groups. The relative expression of miRNA-133a decreased in the placebo and fluticasone groups. The relative expression of miRNA-133a increased in the low-dose anti-IgE, high-dose anti-IgE, fluticasone+anti-IgE and anti-TNF groups. CONCLUSIONS: The results showed that anti-IgE is successful as a treatment. Fluticasone+anti-IgE and anti-TNF were seen to be superior to other therapeutic modalities when used for prophylaxis.

Comparison of inflammatory cytokine release from nasal epithelial cells of non-atopic non-rhinitic, allergic rhinitic and polyp subjects and effects of diesel exhaust particles in vitro

Background. Although studies have reported an association between air pollutants and increased allergic airway diseases, such as allergic rhinitis and nasal polyposis, the underlying mechanisms are not fully understood. A limited number of studies have suggested that diesel exhaust particles (DEP) play a role in atopy and the pathogenesis of allergic upper airway diseases. The aim of this study was to investigate the effect of DEP on inflammatory cytokine release, and mRNA expression of transcription factors such as JNK and NF-Beta in primary nasal epithelial cells (NECs), in vitro. Methods: NECs from non-atopic, non-rhinitic subjects (controls) and patients with allergic rhinitis and nasal polyps were cultured and incubated with 0-100 μg/ml DEP for 24 h. ELISA and RT-PCR were used to assess the release of IL-8, GM-CSF, and RANTES, and mRNA expression for JNK and NF-κB, respectively. Results: Compared to control cells, NECs from subjects with atopic polyps released significantly greater amounts of IL-8 (median = 887 vs. 176.6 pg/μg cellular protein; p < 0.0001) and RANTES (median = 0.191 vs. 0.02 pg/μg cellular protein; p < 0.001). While 50 μg/ml DEP induced release of RANTES in NECs from patients with allergic rhinitis, 100 μg/ml DEP decreased IL-8 levels in NECs from both control and allergic rhinitic subjects. DEP did not affect mRNA expression for JNK and NF-κB from NECs of subjects with polyps. Conclusions: NECs from subjects with various pathologies may respond differently to DEP (AU)

No disponible

Comparison of inflammatory cytokine release from nasal epithelial cells of non-atopic non-rhinitic, allergic rhinitic and polyp subjects and effects of diesel exhaust particles in vitro.

BACKGROUND: Although studies have reported an association between air pollutants and increased allergic airway diseases, such as allergic rhinitis and nasal polyposis, the underlying mechanisms are not fully understood. A limited number of studies have suggested that diesel exhaust particles (DEP) play a role in atopy and the pathogenesis of allergic upper airway diseases. The aim of this study was to investigate the effect of DEP on inflammatory cytokine release, and mRNA expression of transcription factors such as JNK and NF-ß in primary nasal epithelial cells (NECs), in vitro. METHODS: NECs from non-atopic, non-rhinitic subjects (controls) and patients with allergic rhinitis and nasal polyps were cultured and incubated with 0-100µg/ml DEP for 24h. ELISA and RT-PCR were used to assess the release of IL-8, GM-CSF, and RANTES, and mRNA expression for JNK and NF-κB, respectively. RESULTS: Compared to control cells, NECs from subjects with atopic polyps released significantly greater amounts of IL-8 (median=887 vs. 176.6pg/µg cellular protein; p<0.0001) and RANTES (median=0.191 vs. 0.02pg/µg cellular protein; p<0.001). While 50µg/ml DEP induced release of RANTES in NECs from patients with allergic rhinitis, 100µg/ml DEP decreased IL-8 levels in NECs from both control and allergic rhinitic subjects. DEP did not affect mRNA expression for JNK and NF-κB from NECs of subjects with polyps. CONCLUSIONS: NECs from subjects with various pathologies may respond differently to DEP.

The efficacy of single-high dose inhaled corticosteroid versus oral prednisone treatment on exhaled leukotriene and 8-isoprostane levels in mild to moderate asthmatic children with asthma exacerbation

BACKGROUND: The anti-inflammatory effect of high-dose inhaled corticosteroids (ICS) in children with asthma exacerbation is unknown. We aimed to investigate the efficacy of single-high dose ICS versus oral prednisone treatment followed by a course of six day high-dose ICS or oral prednisone (P) treatment on the concentrations of Cys-LTs and 8-isoprostane levels in the exhaled breath condensate (EBC) of children with asthma exacerbation. METHODS: Ninety-four children with moderate-severe asthma exacerbation were evaluated with asthma scores, peak expiratory flow rate (PEF), forced expiratory volume in first second (FEV1) and exhaled Cys-LT and 8-isoprostane levels before and after treatment. EBC was collected from 52 patients before and four hours after treatment with inhaled fluticasone propionate (FP) (4000 μg) or P and after six days of treatment with FP-1000 μg/day or P. Cys-LTs and 8-isoprostane concentrations were determined using a specific immunoassay kit. RESULTS: Both single high-dose FP (n = 59) and p (n = 35) treatment resulted in a significant improvement in asthma score (p < 0.0001), PEF (p < 0.0001), and FEV1 (p < 0.0001). Cys-LT concentration in the EBC decreased significantly both after the initial treatment (p = 0.001), and at the end of the six-day period in the FP group (p < 0.0001). 8-Isoprostane concentration was lower only after six days of treatment with FP-1000 μg/day in the FP group (p = 0.023). There was a significant decrease in exhaled Cys-LTs after four hours (p = 0.012) and six days of P treatment (p = 0.018) in children with asthma exacerbation. CONCLUSIONS: High-dose ICS treatment may be useful in the treatment of children with asthma exacerbation. The effects start as early as after four hours. The suppression of Cys-LTs production contributes to the early effects. Suppression of both Cys-LTs and oxidants may favourably contribute to the effects observed later

No disponible

The efficacy of single-high dose inhaled corticosteroid versus oral prednisone treatment on exhaled leukotriene and 8-isoprostane levels in mild to moderate asthmatic children with asthma exacerbation.

BACKGROUND: The anti-inflammatory effect of high-dose inhaled corticosteroids (ICS) in children with asthma exacerbation is unknown. We aimed to investigate the efficacy of single-high dose ICS versus oral prednisone treatment followed by a course of six day high-dose ICS or oral prednisone (P) treatment on the concentrations of Cys-LTs and 8-isoprostane levels in the exhaled breath condensate (EBC) of children with asthma exacerbation. METHODS: Ninety-four children with moderate-severe asthma exacerbation were evaluated with asthma scores, peak expiratory flow rate (PEF), forced expiratory volume in first second (FEV1) and exhaled Cys-LT and 8-isoprostane levels before and after treatment. EBC was collected from 52 patients before and four hours after treatment with inhaled fluticasone propionate (FP) (4000 µg) or P and after six days of treatment with FP-1000 µg/day or P. Cys-LTs and 8-isoprostane concentrations were determined using a specific immunoassay kit. RESULTS: Both single high-dose FP (n=59) and p (n=35) treatment resulted in a significant improvement in asthma score (p<0.0001), PEF (p<0.0001), and FEV1 (p<0.0001). Cys-LT concentration in the EBC decreased significantly both after the initial treatment (p=0.001), and at the end of the six-day period in the FP group (p<0.0001). 8-Isoprostane concentration was lower only after six days of treatment with FP-1000 µg/day in the FP group (p=0.023). There was a significant decrease in exhaled Cys-LTs after four hours (p=0.012) and six days of P treatment (p=0.018) in children with asthma exacerbation. CONCLUSIONS: High-dose ICS treatment may be useful in the treatment of children with asthma exacerbation. The effects start as early as after four hours. The suppression of Cys-LTs production contributes to the early effects. Suppression of both Cys-LTs and oxidants may favourably contribute to the effects observed later.

Reduced gene expression of bikunin as a prognostic marker for renal cell carcinoma.

AIM: Experimental and clinical studies showed that bikunin, a Kunitz-type protease inhibitor, found in urine and amniotic fluid has a role in spread of tumor cells by providing a significant reduction in the levels of urokinase-type plasminogen activator (uPA) and its specific receptor urokinase-type plasminogen activator receptor (uPAR). The aim of this study was to investigate expression of bikunin at the mRNA level and screen for mutations in exon sequence in renal cell carcinoma (RCC) tissues. MATERIALS AND METHODS: Total RNA and DNA were extracted from paired normal and tumor tissues of total 50 RCC (11 papillary, 8 chromophobe, 26 clear cell, and 5 other types) patients (23 females, mean age: 53.55 ± 14.17; 27 males mean age: 62.1 ± 7.92). Bikunin mRNA levels were detected using semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR). Mutational screening was performed by using single strand conformation polymorphism (SSCP) method and nucleotide sequence analysis. RESULTS: There was a statistically significant decrease in the 25 (50%) of tumor tissues comparing to normal tissues in terms of mRNA levels of bikunin (Wilcoxon signed rank test, p = 0.0337). According to the classification based on subtypes of RCC; clear cell RCC samples displayed a reduced gene expression (p = 0.0148). Additionally, the patients with the age above 50 had low bikunin expression. The SNP rs80057939 spanning 4(th) exon of bikunin was detected in 13 tumor tissues. However, it was not statistically significant (p > 0.05). CONCLUSION: Decreased bikunin mRNA level in renal cells might be associated with poor prognosis of renal carcinoma. Therefore, gene constructs or exogenous administration of bikunin might be a potential adjuvant therapy for RCC treatment.

Relationship between exhaled leukotriene and 8-isoprostane levels and asthma severity, asthma control level, and asthma control test score

OBJECTIVE: Exhaled breath condensate (EBC) is a completely non-invasive method for the collection of airway secretions to measure intense inflammation in the airways of asthmatics. It has been shown that the childhood asthma control test (c-ACT) is a good tool for use in the evaluation of asthmatics. Whether the c-ACT score and asthma control level correlate with the airway inflammation is not well known. We aimed to evaluate the relationship between exhaled cysteinyl leukotrienes (Cys-LTs) and 8-isoprostane levels and asthma severity, asthma control level and c-ACT score in asthmatic children. METHODS: Thirty asthmatic children were evaluated with c-ACT score and pulmonary function tests. Asthma severity and asthma control level were assessed according to GINA. EBC was collected and Cys-LTs and 8-isoprostane concentrations were determined using a specific immunoassay kit. RESULTS: Exhaled 8-isoprostane level in patients with moderate persistent asthma [114 (55-146) pg/ml] was higher than in the mild persistent group [52 (21-91) pg/ml] (p = 0.05, Mann-Whitney U [MWU]). EBC 8-isoprostane in children with 1-4 asthma exacerbations/year [52 (16-80) pg/ml] was significantly lower than in children with > 4 asthma exacerbations/year [114 (57-129) pg/ml] (p < 0.05, MWU). No significant relation was determined between exhaled 8-isoprostane and Cys-LTs levels and c-ACT score and asthma control level. Exhaled 8-isoprostane correlated negatively with bronchodilator response (p = 0.015, r = −0.45). CONCLUSIONS: Exhaled 8-isoprostane, as an oxidative stress specifier, was found to be increased in relation with asthma exacerbation frequency and oxidative stress increases with the severity of asthma. In contrast to asthma severity level, c-ACT score and asthma control level may not reflect airway inflammation

No disponible

The role of bronchial epithelial cell apoptosis in the pathogenesis of COPD.

There is an increased airway inflammation in the pathogenesis of chronic obstructive pulmonary disease (COPD), and it has been suggested that there may also be problem in the apoptosis and renewal of cells. However, there are limited human airway cell studies, in particular those from larger airways such as bronchi. We cultured primary human bronchial epithelial cells (HBECs) from bronchial explants of smokers (n = 6) without COPD and smokers with COPD (n = 8). Apoptosis was studied by fluorescence activated cell sorting. qRT-PCR was used to assess mRNA expression for proteins involving apoptosis including p21(CIP1/WAF1), p53, caspase-8 and caspase-9. Although there was no difference in the rate of viable cells between cells from smokers and COPDs, the level of early apoptotic cells was significantly increased in COPD cells [mean ± standard error of mean (SEM) = 4.86 ± 3.2 %, p = 0.015] as compared to smokers (mean ± SEM = 2.71 ± 1.62 %). In contrast, the rate of late apoptotic cells was significantly decreased in COPD cells (mean ± SEM = 9.82 ± 5.71 %) comparing to smokers (mean ± SEM = 15.21 ± 5.08 %, p = 0.003). Although expression of mRNA for p21(CIP1/WAF1) and caspase-9 was similar in both groups, p53 and caspase-8 mRNA expression was significantly greater in COPD cells. These findings suggest that HBEC apoptosis is increased in COPD, and that this involves p53 and caspase-8 pathways.

Relationship between exhaled leukotriene and 8-isoprostane levels and asthma severity, asthma control level, and asthma control test score.

OBJECTIVE: Exhaled breath condensate (EBC) is a completely non-invasive method for the collection of airway secretions to measure intense inflammation in the airways of asthmatics. It has been shown that the childhood asthma control test (c-ACT) is a good tool for use in the evaluation of asthmatics. Whether the c-ACT score and asthma control level correlate with the airway inflammation is not well known. We aimed to evaluate the relationship between exhaled cysteinyl leukotrienes (Cys-LTs) and 8-isoprostane levels and asthma severity, asthma control level and c-ACT score in asthmatic children. METHODS: Thirty asthmatic children were evaluated with c-ACT score and pulmonary function tests. Asthma severity and asthma control level were assessed according to GINA. EBC was collected and Cys-LTs and 8-isoprostane concentrations were determined using a specific immunoassay kit. RESULTS: Exhaled 8-isoprostane level in patients with moderate persistent asthma [114 (55-146)pg/ml] was higher than in the mild persistent group [52 (21-91)pg/ml] (p=0.05, Mann-Whitney U [MWU]). EBC 8-isoprostane in children with 1-4 asthma exacerbations/year [52 (16-80)pg/ml] was significantly lower than in children with >4 asthma exacerbations/year [114 (57-129)pg/ml] (p<0.05, MWU). No significant relation was determined between exhaled 8-isoprostane and Cys-LTs levels and c-ACT score and asthma control level. Exhaled 8-isoprostane correlated negatively with bronchodilator response (p=0.015, r=-0.45). CONCLUSIONS: Exhaled 8-isoprostane, as an oxidative stress specifier, was found to be increased in relation with asthma exacerbation frequency and oxidative stress increases with the severity of asthma. In contrast to asthma severity level, c-ACT score and asthma control level may not reflect airway inflammation.