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ABSTRACT: To investigate the roles of Th17 lymphocytes and its inflammatory cytokines in airway inflammation exacerbation of murine asthmatic model.
Twenty mice were randomized into control group and asthma group. For the murine asthma model, the mice were sensitized and challenged with ovalbumin (OVA). The control mice were given normal saline alone under the same conditions as the asthma group. We observed the changes in cellular proportions in the bronchoalveolar lavage fluid (BALF) under a light microscope and the histological changes in lung tissue by HE staining. The levels of IL-4, IFN-γ and IL-17 were detected by ELISA. Th1, Th2 and Th17 cells in the peripheral blood were detected by flow cytometry. We did a correlation analysis between Th1, Th2 and Th17 cells in the peripheral blood and neutrophils in BALF.
The total cell number and the percentages of neutrophils, eosinophils and lymphocytes in BALF of the asthmatic mice were significantly higher than those in the control mice (P<0.05). The neutrophils and eosinophils infiltration in pulmonary tissue was also dramatically detected in asthmatic mice. The levels of IL-4 and IL-17 were significantly higher than those in the control mice (P<0.05), while the level of IFN-γ was much lower than in the control mice (P<0.05). Besides, the percentages of Th2 and Th17 cells in peripheral blood were significantly higher in the asthmatic mice than in the control mice (P<0.05). The expression of Th17 was positively correlated with the levels of neutrophils in BALF(r(Th17);=0.394, P<0.05), and the expression of Th1 was negatively correlated with the level of neutrophils in BALF (r(Th1);=-0.446, P<0.05).
Th17 cells could induce the recruitment of inflammatory cytokines and neutrophils into airways, which might aggravate the asthmatic inflammation and be related with asthma exacerbation.
Xi bao yu fen zi mian yi xue za zhi = Chinese journal of cellular and molecular immunology 11/2012; 28(11):1126-8.
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ABSTRACT: To explore the role of interleukin-25(IL-25) in the pathogenesis of eosinophilic asthma (EA) and non-eosinophilic asthma (NEA) through detecting its expression in serum, induced sputum and bronchial epithelial mucosa of asthmatic patients.
Serum and induced sputum were collected from 55 untreated asthmatic patients and 27 healthy control subjects. The asthmatic patients were divided into EA and NEA groups according to sputum eosinophils(EOS) percentage (3% as a dividing point). The level of IL-25 in serum and induced spntum was determined by ELISA; the expression of IL-25 in bronchial epithelium was quantified by immunohistochemistry in biopsied specimens from 10 cases of EA, 10 NEA and 10 controls. Basement membrane thickness as an important index of airway remodeling was detected by HE staining.
Compared with healthy control subjects, the lung function was impaired in patients with EA and NEA. ELISA results showed that the levels of IL-25 in the serum and induced sputum of asthmatic patients were significantly higher than those in healthy subjects (P<0.05). But there were no statistic differences between EA and NEA patients (P>0.05). The immunohistochemical results indicated that the expression of IL-25 was higher in asthmatic bronchial epithelium than in control ones. HE staining showed that the basement membrane thickness increased in EA and NEA patients(P<0.05). Correlation analysis showed that the levels of IL-25 in serum and induced sputum were positively correlated with the average thickness of basement membrane in asthmatic patients.
IL-25 secreted from epithelial cells has the potential to promote airway remodeling in asthma. EOS has nothing to do with the thickness of basement membrane, and it may not be necessary for airway remodeling in asthma.
Xi bao yu fen zi mian yi xue za zhi = Chinese journal of cellular and molecular immunology 06/2012; 28(6):633-6.
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ABSTRACT: Asthma is an epithelial disorder in which T helper 2 (Th2)-type inflammation has a prominent role. Recent studies indicated that a cytokine, thymic stromal lymphopoietin (TSLP), is essential for the development of antigen-induced asthma. The authors used ovalbumin (OVA) sensitization and challenge to induce a murine asthmatic model. The model was confirmed by airway hyperresponsiveness, serum levels of total and OVA-specific immunoglobulin (IgE), histological analysis of lung tissues. The authors found that expression of TSLP was significantly increased in both mRNA and protein levels in mice lungs treated with OVA. The expression of CD40, CD80, and CD86 in bronchoalveolar lavage fluid (BALF) was increased in mice with OVA. Tight correlation between TSLP mRNA and interleukin (IL)-4, IL-5, and IL-13 in BALF was identified. Furthermore, treating mice with TSLP-neutralizing antibody reduced the expression of TSLP mRNA of lungs, CD40, CD80, and CD86 on dendritic cells, and IL-4, IL-5, and IL-13 in the OVA group. This study indicates that TSLP is increased in the airway epithelium in mice treated with OVA. In the lung inflammation model, TSLP activates dendritic cells (DCs) via up-regulation of CD40, CD80, and CD86, then induces the differentiation of prime naive CD4(+) T cells to become proinflammatory Th2 cells. Blocking TSLP is capable of inhibiting the production of Th2 cytokines, thus presents a promising strategy for the treatment of asthma.
Journal of Asthma 03/2010; 47(2):117-23. · 1.52 Impact Factor
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ABSTRACT: Ethyl pyruvate (EP) was recently identified as an experimental therapeutic agent in a wide variety of model systems for inflammation-mediated tissue and cellular injury.
To evaluate the effect of ethyl EP on improving the survival in mice with LPS-induced acute lung injury (ALI).
ALI was induced by administering lipopolysaccharide (LPS) intratracheally. The mice were treated intraperitoneally (i.p.) with 100, 50 and 10 mg/kg EP immediately before intratracheal instillation of LPS, and 100 mg/kg EP was administered 0, 12, 24 and 48 hours after induction of ALI. The mortality rate was recorded and analyzed by the Kaplan-Meier method. Serum tumor necrosis factor (TNF)-alpha, interleukin (IL) -6 and IL-1 beta were measured in bronchial alveolar lavage fluid using an enzyme-linked immunosorbent assay. High-mobility group box 1 levels were measured by Western immunoblotting.
Treatment with EP significantly inhibited the release of HMGB1, TNF-alpha, IL-6 and IL-1beta into bronchoalveolar lavage (BAL) fluids of ALI mice, and reduced the permeability index of the injured lung. High EP doses reduced the mortality from ALI and the permeability index (100 mg/kg and 50 mg/kg EP versus control; P < 0.0001). Early administration of high-dose EP significantly increased survival rate (0, 12 and 24 h versus control; P < 0.0001, P < 0.0001 and P = 0.01 respectively by log-rank test). There was no survival advantage when EP was initiated at 48 h.
Ethyl pyruvate improves survival and reduces the lung permeability index in mice with LPS-induced ALI.
Respiratory research 10/2009; 10:91. · 3.36 Impact Factor
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ABSTRACT: The role of high mobility group box protein 1 (HMGB1) in non-small cell lung cancer (NSCLC) is unknown. We investigated the contributions of HMGB1 in NSCLC, and analyze the correlation between HMGB1 and clinicopathologic outcomes.
A total of 145 patients with diagnosed NSCLC, and 77 patients with diagnosed chronic obstructive pulmonary disease (COPD) (51 chronic bronchitis and 26 obstructive pulmonary emphysema), and 49 healthy volunteers were enrolled from January 2005 through July 2008. HMGB1 levels were analyzed by Western blot analysis.
The mean value of serum HMGB1 levels in 145 patients with lung cancer was 76.1+/-37.0ng/ml and was significantly higher than those in 77 COPD patients (39.8+/-10.8ng/ml), and 49 healthy control (7.7+/-6.1ng/ml, p<0.0001, respectively); The serum HMGB1 levels were 30.2+/-5.9ng/ml, 60.9+/-22.5ng/ml, 99.0+/-23.1ng/ml and 133.4+/-18.9ng/ml in patients with NSCLC of TNM stage I, II, III, and IV. There were significant differences among four groups (p<0.0001). Moreover, the significant positive correlation between the levels of serum HMGB1 and the size of tumor (r=0.799, p<0.001); The serum HMGB1 levels were 57.2+/-28.8ng/ml in patients with NSCLC before operation, and 26.5+/-14.7ng/ml one month after operation (p<0.0001).
Our study suggests that HMGB1 may be a useful clinical marker for evaluating the NSCLC progression and is of potential prognostic value.
Respiratory medicine 06/2009; 103(12):1949-53. · 2.33 Impact Factor
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ABSTRACT: Allergic asthma is a complicated genetic disorder caused by interaction of the acquired and innate immune responses. Acquired immune responses to protein antigens could induce type 2 T lymphocyte-driven responses and result in atopic asthma. Recent studies demonstrated that endotoxin, LPS and air pollution-induced innate immunity induce asthma through Toll-like receptors (TLR). However, the definite mechanism of LPS-induced asthma is still not known. Here, we investigated the effects of different doses of LPS in a mouse model of allergic asthma to define the molecular mechanism of LPS-induced asthma. We found that low doses of LPS in OVA induced significant inflammatory infiltration in lung tissue of asthmatic mice. Histologic studies demonstrated that lungs of these asthmatic mice were characterized by the recruitment of both eosinophils and neutrophils, increased airway mucus secretion and the elevated levels of Th2 cytokines. A high dose of LPS in OVA can induce a Th1 associated response, histologically characterized by neutrophil recruitment, the absence of airway mucus secretion and an increase of IFN-gamma production. Regardless of high or low dose of LPS, TLR4 in alveolar macrophages (AM) was up-regulated in lungs of asthmatic mice. Our data demonstrated that the dose of LPS exposure determines the type of inflammatory response and a low dose of LPS together with OVA augments the antigen-induced lung inflammation in asthma. This study demonstrates that the TLR4 signaling pathway plays a vital role in the development of asthma and indicates the tight connection between endotoxin exposure and asthma prevalence in the clinic.
Journal of Asthma 05/2009; 46(3):229-33. · 1.52 Impact Factor
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ABSTRACT: The aim of this study was to elucidate the role of Found in Inflammatory Zone 1 (FIZZ1, also known as RELM-alpha or resistin-like molecule-alpha) in airway remodeling in asthma. We used a rat model of ovalbumin (OVA) sensitization and challenge to induce lung inflammation and remodeling. Expression of alpha -SMA in the lungs of OVA-treated rats was significantly elevated in the peribronchial regions compared with control saline-treated animals. Expression of FIZZ1 mRNA in alveolar epithelial type II cells (AECII) isolated from OVA-treated animals was higher than in control animals. Forced expression of recombinant FIZZ1 in rat-1 lung fibroblast cell line enhanced production of collagen type I and alpha -SMA compared with control transfected cells. These results suggest that FIZZ1 can induce fibroblasts to express markers of myofibroblast differentiation such as alpha -SMA and collagen type I, which are characteristic of early stages of airway remodeling seen in asthma.
Journal of Asthma 11/2008; 45(8):648-53. · 1.52 Impact Factor
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ABSTRACT: To study the activation of macrophage and upregulation of costimulatory molecule of CD40 in lipopolysaccharide- (LPS-) induced acute lung injury (ALI) model, and to investigate the pathogenecy of ALI, mice were randomly divided into two groups. ALI model was created by injecting 0.2 mg/kg LPS in phosphate saline (PBS) in trachea. The pathologic changes of mice lungs were observed by HE staining at 24 and 48 hours after LPS treatment, then the alveolar septum damage, abnormal contraction, alveolar space hyperemia, and neutrophils or other inflammatory cells infiltration in the LPS group, but not in the control group, were observed. The expression of CD40 mRNA and CD40 protein molecules were higher in LPS group as compared to the control group by Northern blot and flow cytometry, respectively. Expression of Toll-like receptor-4 (TLR4) in activated macrophage (AMPhi) was higher in LPS group as compared to the control group by RT-PCR. The activation of NF-kappaB binding to NF-kappaB consensus oligos increased in LPS group by EMSA in macrophage. The concentrations of TNF-alpha, MIP-2, and IL-1beta cytokines from bronchoalveolar lavage fluid (BALF) were increased significantly in LPS group as compared to the control group by ELISA. The activation of AM and upregulation of costimulatory molecule CD40 induced all kinds of inflammatory cytokines releasing, then led to ALI. Therefore, both of them played vital role in the process of development of ALI.
Journal of Biomedicine and Biotechnology 02/2008; 2008:852571. · 2.44 Impact Factor
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Chinese medical journal 09/2006; 119(16):1396-9. · 0.86 Impact Factor
