Involvement of type II pneumocytes in the pathogenesis of chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality, but the cellular and molecular mechanisms are still not fully understood. Type II pneumocytes are identified as the synthesizing cells of the alveolar surfactant, which has important properties in maintaining alveolar and airway stability. Lung surfactant can reduce the surface tension and prevent alveolar collapse and the airway walls collapse. Pulmonary surfactant components play important roles in normal lung function and inflammation in the lung. Surfactant has furthermore been shown to modulate the process of innate host defense, including suppression of cytokine secretion and transcription factor activation, in the inflammatory network of COPD. Abnormalities of lung surfactant might be one of the mechanisms leading to increased airway resistance in COPD. The increased expression of Granzyme A and B was found in lung tissues of patients with COPD and type II pneumocytes was proposed to be involved in the pathogenesis of COPD. These novel findings provide new sights into the role of the type II pneumocytes in the pathogenesis of COPD.

[Effect of QTY06 on lipopolysaccharide-induced chronic airway inflammation and MUC5ac secretion in rats].

OBJECTIVE: To investigate the effect of synthetic drug QTY06 on chronic airway inflammation and mucoprotein expression induced by intratracheal (i.t) instillation of lipopolysaccharide (LPS). METHODS: Chronic airway inflammation was induced by i.t instillation of LPS in rats. Phospholipids content and the number of leucocytes in bronchoalveolar lavage fluid (BALF), pathological and immunochemical changes were examined 3 weeks after LPS instillation. The effect of QTY06 on chronic airway inflammation was observed. RESULT: After treatment with QTY06, phospholipids in BALF was significantly increased, and the percentages of neutrophils and lymphocytes were decreased as well as the total number of leucocytes. Compared with the model group, pathological examination showed that tracheitis, bronchitis and pulmonary interstitial inflammation in QTY06 groups were significantly attenuated; epithelial damage was alleviated, infiltration of inflammatory cells reduced and the number of goblet cells decreased. QTY06 significantly decreased MUC5ac expression in trachea and bronchiole epithelium, and reduced the optical density and mucins area (%) as detected by image analysis in rats with chronic airway inflammation. CONCLUSION: QTY06 can reduce and inhibit the chronic airway inflammation induced by LPS in rats, and increase the content of phospholipids in pulmonary surfactant and inhibit the hypersecretion of airway mucins.

[Effect of Spearmint oil on inflammation, oxidative alteration and Nrf2 expression in lung tissue of COPD rats].

OBJECTIVE: To investigate the effect of Spearmint oil on inflammation, oxidative alteration and Nrf2 expression in rats with chronic obstructive pulmonary disease(COPD). METHODS: COPD model was induced by intratracheal instillation of Klebsiella pneumonia and lipopolysaccharide (LPS) for 12 weeks in rats, and COPD rats were treated with Spearmint oil for 3 weeks. After COPD was induced, the pathological changes, changes in leucocyte number in blood and bronchoalveolar lavage fluid (BALF), MDA in lung homogenate and Nrf2 expression were observed. The effects of Spearmint oil on these changes were determined. RESULT: Spearmint oil 100 mg*kg(-1)significantly reduced leucocyte numbers in BALF, and attenuated bronchiolitis, pulmonary interstitial inflammation and inflammation cell infiltration. Spearmint oil 30-300 mg*kg(-1)decreased the destruction of pulmonary alveolus and the thickness of bronchioles walls, and inhibited goblet cell proliferation. Spearmint oil significantly reduced MDA in lung homogenate, and decreased the expression of Nrf2 protein in lung tissues. CONCLUSION: Spearmint oil has protective effect on lung injury in COPD rats, since it improves pulmonary inflammation,oxidative alteration, and enhances Nrf2 protein expression.

Inhibitory effect of 1,8-cineol (eucalyptol) on Egr-1 expression in lipopolysaccharide-stimulated THP-1 cells.

AIM: To study the effects of 1,8-cineol (eucalyptol) on the expression of early growth response factor-1 (Egr-1) and NF-kappaB in the human monocyte THP-1 cell line stimulated by lipopolysaccharide (LPS). METHODS: The THP-1 cells were incubated with serial doses of 1,8-cineol (1, 10, and 100 mg/L, 30 min) before being stimulated with LPS (1 mg/L, 30 min). The localization of Egr-1 in the THP-1 cells was detected by immunofluorescence and a laser scanning confocal microscope. The expression of Egr-1 in the nuclei and whole cell, and NF-kappaB in the nuclei, were measured by Western blot analysis. RESULTS: When stimulated by LPS, the FITC-labeled Egr-1 was detected mainly in the nuclei. Moreover, the expression of Egr-1 in the whole cell increased markedly compared with the control cells. 1,8-Cineol pretreatment decreased the expression of Egr-1 in both the nuclei and whole cell of the LPS-stimulated THP-1 cells, and this effect was concentration-dependent, but there was no reaction on the expression of NF-kappaB in the nuclei protein in the LPS-stimulated THP-1 cells. CONCLUSION: In a concentration-dependent manner, 1,8-Cineol reduces LPS-induced Egr-1 expression in nuclei and in whole cell of THP-1 cells, but shows no effect on NF-kappaB expression.

[The expression of TLR4 in rat acute lung injury induced by lipopolysaccharide and the influence of Eucalyptus globulus oil].

OBJECTIVE: To observe the distribution of toll-like receptor 4 (TLR4) in rats' respiratory tract. To study the influence of LPS and Eucalyptus globulus oil on the distribution of TMR4. METHOD: The Sprague-Dawley rats were intratracheally instilled with lipopolysaccharide (LPS,2 mg x kg(-1) per day) for two days to induce acute lung injury. The rats were sacrificed at 72 hours after LPS instillation. Lung morphology was studied. Leukocytes in Bronchoalveolar lavage fluid (BALF) were measured and TLR4 were detected by immunohistochemistry. RESULT: The result of immunohistochemistry showed that TLR4 distributed widely in common rats' respiratory tract. In the group of acute lung injury, the number of leucocyte in BALF was increased apparently, the inflammation in bronchus and bronchioles was more apparently than that of the control group in morphology. And the expression of TLR4 was reinforced in main bronchus and bronchioles. In the group of E. globules oil (300 mg x kg(-1)), the leucocyte number was decreased apparently in BALF, the inflammation was lightened and the expression of TLR4 decreased as compared with the group of models. CONCLUSION: The expression of TLR4 distributes widely in rats' respiratory tract. The stimulation of LPS can reinforce the expression of TLR4. The E. globules oil can reduce the increase of TLR4 induced by LPS in bronchioles.

Effect of alpha-pinene on nuclear translocation of NF-kappa B in THP-1 cells.

AIM: To study the effects of alpha-pinene on nuclear translocation of nuclear factor-kappa B (NF-kappa B) and the expression of the inhibitor of NF-kappa B (I kappa B alpha) in human monocyte THP-1 cell line. METHODS: THP-1 cells were incubated with alpha-pinene (1, 10, and 100 mg/L, for 30 min) before being stimulated with lipopolysaccharide (LPS, 1 mg/L, 30 min). The location of NF-kappa B p65 subunit (NF-kappa B/p65) in THP-1 cells was detected by immunofluorescence and laser scanning confocal microscope (LSCM). The expression of NF-kappa B/p65 in nuclei and that of I kappa B alpha in cytoplasm were measured by Western-blot analysis. RESULTS: The majority of FITC-labelled NF-kappa B/p65 was located in the nuclei being stimulated with LPS. Whereas, no such fluorescence was seen in the nuclei of the groups pretreated with alpha-pinene or control cells. alpha-Pinene pretreatment decreased the NF-kappa B/p65 nuclear translocation in LPS-stimulated THP-1 cells, and this effect was dose-dependent, but there was no reaction in LPS-unstimulated THP-1 cells. alpha-Pinene pretreatment increased I kappa B alpha protein level in cytoplasm, compared with that in LPS-stimulated THP-1 cells. CONCLUSION: In a dose-related fashion, alpha-pinene inhibits the nuclear translocation of NF-kappa B induced by LPS in THP-1 cells, and this effect is partly due to the upregulation of I kappa B alpha expression.

[Effect of Eucalyptus globulus oil on lipopolysaccharide-induced chronic bronchitis and mucin hypersecretion in rats].

OBJECTIVE: To study the effect of Eucalyptus globulus oil on bronchiolitis and mucin hypersecretion in chronic bronchitis induced by lipopolysaccharide in rats. METHOD: Rat model was established by intratracheal instillation of lipopolysaccharide 0.2 mg. Pathological changes, alteration in bronchoalveolar lavage fluid (BALF) and immunohistochemistry characters were examined after 3 weeks and the effect of E. globulus oil was observed. RESULT: Characters of pathological manifestations of chronic bronchitis were found after instillation of LPS. Inflammatory cell infiltration and bronchiolitis severity were significantly reduced after administration of E. globulus oil. Especially in 300 mg x kg(-1) treated rats, there were significant decreases of mucin content in BALF and MUC5ac expression in trachea and bronchiole epithelium. Optical density and mucins area% detected by image analysis system were apparently lower than those in model group. CONCLUSION: E. globulus oil has the anti-inflammatory effect on chronic bronchitis induced by lipopolysaccharide in rats and the inhibitio effect on hypersecretion of airway mucins.

[Effect of eucalyptus globulus oil on activation of nuclear factor-kappaB in THP-1 cells].

OBJECTIVE: To study the effect of eucalyptus globulus oil on the activity of nuclear factor-kappaB(NF-kappaB) in THP-1 cell line. METHODS: THP-1 cells were cultured with or without eucalyptus globulus oil at different concentrations (1, 10, 100 mg x L(-1), 30 min) before being stimulated with lipopolysaccharide (LPS, 1 mg x L(-1), 30 min). The location of NF-kappaB p65 subunit (NF-kappaB/p65) in THP-1 cells was detected by indirect immunofluorescence and laser scanning confocal microscope. The expression of NF-kappaB/p65 in nuclei was measured by Western-blot analysis. RESULT: The FITC-label NF-kappaB/p65 was mainly located in the nuclei after THP-1 cells were stimulated with LPS. Whereas, no fluorescence were seen in the nuclei of cells pretreated with eucalyptus globulus oil. This effect on NF-kappaB/p65 nuclear translocation was in a concentration dependent manner. CONCLUSION: Eucalyptus globulus oil inhibits the nuclear translocation of NF-kappaB induced by LPS in THP-1 cells.

[The effect of silicon dioxide on the activation of nuclear factor-kappaB in THP-1 cells].

OBJECTIVE: To study the effect of silicon dioxide (SiO(2)) on the activation of nuclear factor-kappaB (NF-kappaB) in THP-1 cell line. METHODS: THP-1 cells were incubated with a series of doses of SiO(2) (0, 100, 200 micro g/ml). The location of NF-kappaB p65 subunit (NF-kappaB/p65) in THP-1 cells was detected by immunofluorescence and laser scanning confocal microscope (LSCM). The expression of NF-kappaB/p65 in nuclei was measured by Western blot analysis. RESULTS: The majority of fluorescein isothiocyanate (FITC)-labelled NF-kappaB/p65 located in the nuclei 30 min after stimulation by 100 micro g/ml SiO(2), whereas the FITC-labelled NF-kappaB/p65 were mainly seen in the plasma of normal control cells. The expression of NF-kappaB/p65 in THP-1 nuclear protein was low in control group (0 micro g/ml SiO(2)) while it increased after stimulation by 100 micro g/ml SiO(2) and 200 micro g/ml SiO(2) for 15 min and 30 min. The level of NF-kappaB/p65 was comparatively increased with the increasing of doses and time. Lipopolysaccharides (LPS), an activator of NF-kappaB, had similar effect as SiO(2) on the activation of NF-kappaB/p65 in THP-1 cells. CONCLUSION: SiO(2) could activate and internalize NF-kappaB in the THP-1 cell line.