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Sample records for bronchial epithelium induced

  1. Mechanisms of aldehyde-induced bronchial reactivity: role of airway epithelium

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    Leikauf, G.D. (Department of Environmental Health, University of Cincinnati Medical Center, OH (United States))

    1992-02-01

    To investigate the relative irritant potencies of inhaled aldehydes, guinea pigs were exposed to formaldehyde or acrolein and specific total pulmonary resistance and bronchial reactivity to intravenous acetylcholine were assessed. The mechanisms associated with these responses were investigated by analyzing morphologic and biochemical changes in airway epithelial cells after in vivo and in vitro exposures. Immediately after exposure to formaldehyde or acrolein, specific resistance increased transiently and returned to control values within 30 to 60 minutes. Bronchial hyperreactivity, assessed by the acetylcholine dose necessary to double resistance, increased and became maximal two to six hours after exposure to at least 9 parts per million2 (ppm) formaldehyde or at least 1 ppm acrolein for two hours. The effect of exposure to 3 ppm formaldehyde for two hours was less than the effect of exposure to 1 ppm formaldehyde for eight hours; thus, extended exposures produced a disproportionate heightening of bronchial reactivity. Bronchial hyperreactivity often persisted for longer than 24 hours. Increases in three bronchoconstrictive eicosanoids, prostaglandin F2 alpha, thromboxane B2, and leukotriene C4, occurred immediately after exposure, whereas an influx of neutrophils into lavage fluid occurred 24 hours later. Histological examination of the tracheal epithelium and lamina propria also demonstrated a lack of inflammatory cell infiltration. Treatment with leukotriene synthesis inhibitors and receptor antagonists inhibited acrolein-induced hyperreactivity, supporting a causal role for these compounds in this response. Acrolein also stimulated eicosanoid release from bovine epithelial cells in culture. However, the profile of metabolites formed differed from that found in lavage fluid after in vivo exposure.

  2. Circular flow patterns induced by ciliary activity in reconstituted human bronchial epithelium

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    Viallat, Annie; Khelloufi, Kamel; Gras, Delphine; Chanez, Pascal; Aix Marseille Univ., CNRS, CINaM, Marseille, France Team; Aix Marseille Univ., CNRS, Inserm, LAI, Marseille, France Team

    2016-11-01

    Mucociliary clearance is the transport at the surface of airways of a complex fluid layer, the mucus, moved by the beats of microscopic cilia present on epithelial ciliated cells. We explored the coupling between the spatial organisation and the activity of cilia and the transport of surface fluids on reconstituted cultures of human bronchial epithelium at air-liquid interface, obtained by human biopsies. We reveal the existence of stable local circular surface flow patterns of mucus or Newtonian fluid at the epithelium surface. We find a power law over more than 3 orders of magnitude showing that the average ciliated cell density controls the size of these flow patterns, and, therefore the distance over which mucus can be transported. We show that these circular flow patterns result from the radial linear increase of the local propelling forces (due to ciliary beats) on each flow domain. This linear increase of local forces is induced by a fine self-regulation of both cilia density and orientation of ciliary beats. Local flow domains grow and merge during ciliogenesis to provide macroscopic mucus transport. This is possible only when the viscoelastic mucus continuously exerts a shear stress on beating cilia, revealing a mechanosensitive function of cilia. M. K. Khelloufi thanks the society MedBioMed for financial support. This work was supported by the ANR MUCOCIL project, Grant ANR-13-BSV5-0015 of the French Agence Nationale de la Recherche.

  3. Radon induced hyperplasia: effective adaptation reducing the local doses in the bronchial epithelium.

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    Madas, Balázs G

    2016-09-01

    There is experimental and histological evidence that chronic irritation and cell death may cause hyperplasia in the exposed tissue. As the heterogeneous deposition of inhaled radon progeny results in high local doses at the peak of the bronchial bifurcations, it was proposed earlier that hyperplasia occurs in these deposition hot spots upon chronic radon exposure. The objective of the present study is to quantify how the induction of basal cell hyperplasia modulates the microdosimetric consequences of a given radon exposure. For this purpose, computational epithelium models were constructed with spherical cell nuclei of six different cell types based on histological data. Basal cell hyperplasia was modelled by epithelium models with additional basal cells and increased epithelium thickness. Microdosimetry for alpha-particles was performed by an own-developed Monte-Carlo code. Results show that the average tissue dose, and the average hit number and dose of basal cells decrease by the increase of the measure of hyperplasia. Hit and dose distribution reveal that the induction of hyperplasia may result in a basal cell pool which is shielded from alpha-radiation. It highlights that the exposure history affects the microdosimetric consequences of a present exposure, while the biological and health effects may also depend on previous exposures. The induction of hyperplasia can be considered as a radioadaptive response at the tissue level. Such an adaptation of the tissue challenges the validity of the application of the dose and dose rate effectiveness factor from a mechanistic point of view. As the location of radiosensitive target cells may change due to previous exposures, dosimetry models considering the tissue geometry characteristic of normal conditions may be inappropriate for dose estimation in case of protracted exposures. As internal exposures are frequently chronic, such changes in tissue geometry may be highly relevant for other incorporated radionuclides.

  4. Bronchial epithelial spheroids: an alternative culture model to investigate epithelium inflammation-mediated COPD

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    Gangloff Sophie C

    2007-11-01

    Full Text Available Abstract Background Chronic obstructive pulmonary disease (COPD is characterized by abnormal lung inflammation that exceeds the protective response. Various culture models using epithelial cell lines or primary cells have been used to investigate the contribution of bronchial epithelium in the exaggerated inflammation of COPD. However, these models do not mimic in vivo situations for several reasons (e.g, transformed epithelial cells, protease-mediated dissociation of primary cells, etc.. To circumvent these concerns, we developed a new epithelial cell culture model. Methods Using non transformed non dissociated bronchial epithelium obtained by bronchial brushings from COPD and non-COPD smokers, we developed a 3-dimensional culture model, bronchial epithelial spheroids (BES. BES were analyzed by videomicroscopy, light microscopy, immunofluorescence, and transmission electron microscopy. We also compared the inflammatory responses of COPD and non-COPD BES. In our study, we chose to stimulate BES with lipopolycaccharide (LPS and measured the release of the pro-inflammatory mediators interleukin-8 (IL-8 and leukotriene B4 (LTB4 and the anti-inflammatory mediator prostaglandin E2 (PGE2. Results BES obtained from both COPD and non-COPD patients were characterized by a polarized bronchial epithelium with tight junctions and ciliary beating, composed of basal cells, secretory cells and ciliated cells. The ciliary beat frequency of ciliated cells was not significantly different between the two groups. Of interest, BES retained their characteristic features in culture up to 8 days. BES released the inflammatory mediators IL-8, PGE2 and LTB4 constitutively and following exposure to LPS. Interestingly, LPS induced a higher release of IL-8, but not PGE2 and LTB4 in COPD BES (p Conclusion This study provides for the first time a compelling evidence that the BES model provides an unaltered bronchial surface epithelium. More importantly, BES represent an

  5. Keratinocyte growth factor improves alterations of lung permeability and bronchial epithelium in allergic rats.

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    Tillie-Leblond, I; Gosset, P; Le Berre, R; Janin, A; Prangère, T; Tonnel, A B; Guery, B P H

    2007-07-01

    Chronic allergic asthma is associated with marked inflammatory reaction, microvascular leakage and epithelium injury. As previously shown in a rat model of chronic asthma, these alterations increase lung permeability and distal airway fluid clearance. Keratinocyte growth factor (KGF) has been shown to induce epithelial cell proliferation and to protect from acute lung injuries. Therefore, the current authors evaluated the potential role of KGF treatment on lung permeability and airway inflammation in rats with chronic asthma. KGF (1 mg x kg(-1)) was administered intravenously before the last ovalbumin (OVA) challenge in sensitised rats. Permeability was assessed by the leak of radiolabelled albumin from the alveolar and systemic compartments. Histopathological analysis was also performed. Treatment with KGF decreased the leak of both markers and decreased the level of extravascular lung water in sensitised rats challenged with OVA. KGF treatment also reduced the inflammatory cell number in bronchoalveolar lavage fluid but not in bronchial mucosa. KGF markedly limited the allergen-induced alterations in epithelium integrity and the expression of the intercellular junction proteins beta-catenin and zonula occludens protein-1. In conclusion, keratinocyte growth factor administration markedly limits lung permeability and airway inflammation, an effect associated with a decrease in epithelium alterations during chronic allergic asthma. These data open new prospects in the therapeutic strategy of asthma.

  6. Early suppression of NFkappaB and IL-8 in bronchial epithelium after ozone exposure in healthy human subjects.

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    Bosson, Jenny; Blomberg, Anders; Pourazar, Jamshid; Mudway, Ian S; Frew, Anthony J; Kelly, Frank J; Sandström, Thomas

    2009-09-01

    Exposure to elevated concentrations of ozone, a common air pollutant, has been associated with numerous adverse health effects. We have previously reported the time-course of ozone-induced airway inflammation, demonstrating an early up-regulation of vascular endothelial adhesion molecules in bronchial mucosa at 1.5 hours, followed by a neutrophilic infiltration 6 hours after exposure to 0.2 ppm ozone. We hypothesized that the neutrophilic infiltration in the bronchial mucosa would reflect an early increase in bronchial epithelial expression of redox-sensitive transcription factors and kinases regulating neutrophil chemoattractant expression. To test this hypothesis, endobronchial biopsies were obtained from healthy human subjects (n = 11) 1.5 hours after 0.2 ppm of ozone and filtered air exposures (lasting for 2 hours) and stained for mitogen-activated protein kinases (MAPKs), transcription factors, and neutrophil chemoattractants. Total epithelial staining was quantified, as well as the extent of nuclear translocation. Contrary to expectation, ozone significantly suppressed total and nuclear expression of nuclear factor kappaB (NFkappaB) in bronchial epithelial cells (p = 0.02 and p = 0.003 respectively). Similarly, the total staining for phosphorylated C-jun was suppressed (p = 0.021). Expression of interleukin 8 (IL-8) in the bronchial epithelium was likewise decreased after ozone (p = 0.018), while GRO-alpha, ENA-78, C-fos, p-p38, p-JNK, and p-ERK stainings were unchanged. These data suggest that the redox-sensitive NFkappaB and activator protein 1 (AP-1) pathways within the human bronchial epithelium do not seem to be involved in the early inflammatory cell recruitment pathways in healthy subjects exposed to ozone.

  7. [Quantitative image analysis in pulmonary pathology - digitalization of preneoplastic lesions in human bronchial epithelium (author's transl)].

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    Steinbach, T; Müller, K M; Kämper, H

    1979-01-01

    The report concerns the first phase of a quantitative study of normal and abnormal bronchial epithelium with the objective of establishing the digitalization of histologic patterns. Preparative methods, data collecting and handling, and further mathematical analysis are described. In cluster and discriminatory analysis the digitalized histologic features can be used to separate and classify the individual cases into the respective diagnostic groups.

  8. Cavitary Lung Cancer Lined with Normal Bronchial Epithelium and Cancer Cells

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    Goto, Taichiro; Maeshima, Arafumi; Oyamada, Yoshitaka; Kato, Ryoichi

    2011-01-01

    Reports of cavitary lung cancer are not uncommon, and the cavity generally contains either dilated bronchi or cancer cells. Recently, we encountered a surgical case of cavitary lung cancer whose cavity tended to enlarge during long-term follow-up, and was found to be lined with normal bronchial epithelium and adenocarcinoma cells.

  9. Apoptosis in normal bronchial respiratory epithelium between certainties and uncertainties

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    Adriana Grigoras

    2010-02-01

    Full Text Available The respiratory epithelium lines the conducting airways and functions as a selective barrier interposed between external environment and human body. It is exposed to various aggressive factors such as viral and bacterial microorganisms, or cigarette smoke and other inhaled noxious substances. The normal airway epithelium has its own mechanisms that maintain the integrity of the epithelial barrier and it is relatively refractory to a number of apoptotic stimuli. The up to date data about apoptosis in normal airway epithelium are limited, especially regarding the regulatory factors of this process. The current knowledge concerning the airway epithelium apoptosis regulation needs to be further studied by exploring the Bcl-2 superfamily members, Zn, p21, or peroxiredoxine V and pirine.

  10. Discrepancy between mRNA and Protein Expression of Neutrophil Gelatinase-Associated Lipocalin in Bronchial Epithelium Induced by Sulfur Mustard

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    Majid Ebrahimi

    2010-01-01

    Full Text Available Sulfur mustard (SM is a potent vesicant that has been employed as a chemical weapon in various conflicts during the 20th century. More recently, mustard was used in the Iraq conflict against Iranian troops and civilians. At the present time there are more than 40.000 people suffering from pulmonary lesions special bronchiolitis obliterans (BOs due to mustard gas. SM increases the endogenous production of reactive oxygen species (ROS. Neutrophil Gelatinase-associated Lipocalin 2 (Lcn2, NGAL is a member of the lipocalin superfamily for which a variety of functions such as cellular protection against oxidative stress have been reported. Ten normal and Twenty SM-induced COPD patient individuals were studied. Assessment of NGAL expressions in healthy and the patients endobrinchial biopsies were performed by semiquantitative RT-PCR, real-time RT-PCR, and Immunohistochemistry analysis. While Normal control samples expressed same level of mRNA NGAL, expression level of mRNA-NGAL was upregulated about 1.4- to 9.8-folds compared to normal samples. No significant immunoreactivity was revealed in both samples. As we are aware this is the first report of induction of NGAL in patients exposed to SM. NGAL may play an important role in cellular protection against oxidative stress toxicity induced by mustard gas in airway wall of patients.

  11. HIV Infects Bronchial Epithelium and Suppresses Components of the Mucociliary Clearance Apparatus

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    Chinnapaiyan, S.; Parira, T.; Dutta, R.; Agudelo, M.; Morris, A.; Nair, M.; Unwalla, H. J.

    2017-01-01

    Recurrent lung infections and pneumonia are emerging as significant comorbidities in the HIV-infected population in the era of combination antiretroviral therapy (cART). HIV infection has been reported to suppress nasal mucociliary clearance (MCC). Since the primary components driving nasal MCC and bronchial MCC are identical, it is possible that bronchial MCC is affected as well. Effective MCC requires optimal ciliary beating which depends on the maintenance of the airway surface liquid (ASL), a function of cystic fibrosis transmembrane conductance regulator (CFTR) activity and the integrity of the signaling mechanism that regulates ciliary beating and fluid secretion. Impairment of either component of the MCC apparatus can compromise its efficacy and promote microbial colonization. We demonstrate that primary bronchial epithelium expresses HIV receptor CD4 and co-receptors CCR5 and CXCR4 and can be infected by both R5 and X4 tropic strains of HIV. We show that HIV Tat suppresses CFTR biogenesis and function in primary bronchial epithelial cells by a pathway involving TGF-β signaling. HIV infection also interferes with bronchial epithelial cell differentiation and suppresses ciliogenesis. These findings suggest that HIV infection suppresses tracheobronchial mucociliary clearance and this may predispose HIV-infected patients to recurrent lung infections, pneumonia and chronic bronchitis. PMID:28060951

  12. Study of the Changes on Tree Shrew Bronchial Epithelium Induced by Xuanwei Bituminous Coal Dust%宣威烟煤粉尘诱发树鼩支气管粘膜上皮改变的研究

    Institute of Scientific and Technical Information of China (English)

    陈小波; 贺猛; 李光剑; 周永春; 赵光强; 雷玉洁; 杨凯云; 田琳玮; 黄云超

    2015-01-01

    背景与目的肺癌在许多国家和地区已成为发病率和死亡率最高的恶性肿瘤,建立科学合适的肺癌动物模型,用以模拟出与人类肺癌的病因、发病机制、发展过程相似的动物模型是亟待解决的问题。通过宣威烟煤粉尘PM10(particulate matter with diameters of 10μm or less, PM10)对树鼩支气管上皮的影响,探索建立宣威烟煤粉尘致肺癌模型的可行性。方法健康成年树鼩,切开颈部皮肤,充分暴露甲状软骨,于甲状软骨上方薄弱处,采用特制灌注针行穿刺的方法进行气管内试剂灌注。定期行X线检查,观察肺部影像学改变,处死动物行肺组织病理检查,观察灌注后支气管上皮改变情况。结果烟尘处理组树鼩灌注药物后1周内开始死亡,空白对照组、溶剂对照组树鼩灌注后至实验结束无异常死亡。定期处死树鼩行肺组织HE染色切片病理检查,空白对照组及溶剂对照组无明显病理改变,烟尘处理组树鼩肺组织可见支气管粘膜上皮过度增生-鳞状化生-不典型增生-早期浸润癌的病理变化过程。结论宣威烟煤粉尘可以导致树鼩支气管上皮出现支气管粘膜上皮过度增生-鳞状化生-不典型增生-早期浸润癌的病理变化,应用宣威烟煤粉尘PM10行气管内灌注可以诱发树鼩肺癌。可以建立肺癌模型。%Background and objective Lung cancer is the type of cancer with the highest incidence and mortality in numerous countries and regions. Establishing an appropriate animal model that can be used to simulate lung cancer etiology, pathogenesis, and similar processes, is urgent. We explore the feasibility of establishing a lung cancer model induced by Xuan-wei bituminous coal dust PM10 (particulate matter with diameters of 10 μm or less), which affects bronchial epithelium of tree shrews.Methods hTe neck skin of adult tree shrews is dissected, and the thyroid cartilage is fully

  13. Role of aberrant metalloproteinase activity in the pro-inflammatory phenotype of bronchial epithelium in COPD

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    Postma Dirkje S

    2011-08-01

    Full Text Available Abstract Background Cigarette smoke, the major risk factor for COPD, is known to activate matrix metalloproteinases in airway epithelium. We investigated whether metalloproteinases, particularly A Disintegrin and Metalloproteinase (ADAM17, contribute to increased pro-inflammatory epithelial responses with respect to the release of IL-8 and TGF-α, cytokines implicated in COPD pathogenesis. Methods We studied the effects of cigarette smoke extract (CSE and metalloproteinase inhibitors on TGF-α and IL-8 release in primary bronchial epithelial cells (PBECs from COPD patients, healthy smokers and non-smokers. Results We observed that TGF-α was mainly shed by ADAM17 in PBECs from all groups. Interestingly, IL-8 production occurred independently from ADAM17 and TGF-α shedding, but was significantly inhibited by broad-spectrum metalloproteinase inhibitor TAPI-2. CSE did not induce ADAM17-dependent TGF-α shedding, while it slightly augmented the production of IL-8. This was accompanied by reduced endogenous inhibitor of metalloproteinase (TIMP-3 levels, suggesting that CSE does not directly but rather indirectly alter activity of ADAM17 through the regulation of its endogenous inhibitor. Furthermore, whereas baseline TGF-α shedding was lower in COPD PBECs, the early release of IL-8 (likely due to its shedding was higher in PBECs from COPD than healthy smokers. Importantly, this was accompanied by lower TIMP-2 levels in COPD PBECs, while baseline TIMP-3 levels were similar between groups. Conclusions Our data indicate that IL-8 secretion is regulated independently from ADAM17 activity and TGF-α shedding and that particularly its early release is differentially regulated in PBECs from COPD and healthy smokers. Since TIMP-2-sensitive metalloproteinases could potentially contribute to IL-8 release, these may be interesting targets to further investigate novel therapeutic strategies in COPD.

  14. Modulating Effect of Peptide Therapy on the Morphofunctional State of Bronchial Epithelium in Rats with Obstructive Lung Pathology.

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    Kuzubova, N A; Lebedeva, E S; Dvorakovskaya, I V; Surkova, E A; Platonova, I S; Titova, O N

    2015-09-01

    On the model of chronic obstructive pulmonary disease, the effect of therapy with low-molecular-weight peptides on restructuring and functional activity of bronchial epithelium for restoring the immune and barrier function of the lungs and prevention of inflammatory process progression was studied. Chronic obstructive pulmonary disease was modeled in rats by 60-day intermittent exposure to NO2. Administration of tetrapeptide Bronchogen for 1 month eliminates symptoms of remodeling of the bronchial epithelium and lung tissue typical of chronic obstructive pulmonary disease (goblet cell hyperplasia, squamous metaplasia, lymphocytic infiltration and emphysema, and restoration of ciliated cells). Enhanced production of secretory IgA, a local immunity marker, attested to normalization of functional activity of bronchial epithelium, while normalization of cell composition and profile of proinflammatory cytokines in the bronchoalveolar space reflected reduction of neutrophilic inflammation.

  15. Increased polysomy of chromosome 7 in bronchial epithelium from patients at high risk for lung cancer

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    Belinsky, S.A.; Neft, R.E.; Lechner, J.F. [and others

    1995-12-01

    Current models of carcinogenesis suggest that tissues progress through multiple genetic and epigenetic changes which ultimately lead to development of invasive cancer. Epidemiologic studies of Peto, R.R. and J.A. Doll indicate that the accumulation of these genetic changes over time, rather than any single unique genetic change, is probably responsible for development of the malignant phenotype. The bronchial epithelium of cigarette smokers is diffusely exposed to a broad spectrum of carcinogens, toxicants, and tumor promoters contained in tobacco smoke. This exposure increases the risk of developing multiple, independent premalignant foci throughout the lower respiratory tract that may contain independent gene aberrations. This {open_quotes}field cancerization{close_quotes} theory is supported by studies that have demonstrated progressive histologic changes distributed throughout the lower respiratory tract of smokers. A series of autopsy studies demonstrated that cigarette smokers exhibit premalignant histologic changes ranging from hyperplasia and metaplasia to severe dysplasia and carcinoma in situ diffusely throughout the bronchial mucosa. The proximal bronchi appear to exhibit the greatest number of changes, particularly at bifurcations. The results described are the first to quantitate the frequency for a chromosome aberration in {open_quotes}normal{close_quotes} bronchial epithelial cells.

  16. Increased cytochrome P450 and aryl hydrocarbon receptor in bronchial epithelium of heavy smokers with non-small cell lung carcinoma carries a poor prognosis.

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    Oyama, Tsunehiro; Sugio, Kenji; Uramoto, Hidetaka; Iwata, Teruo; Onitsuka, Takamitsu; Isse, Toyohi; Nozoe, Tadahiro; Kagawa, Norio; Yasumoto, Kosei; Kawamoto, Toshihiro

    2007-05-01

    Smoking induces mutations via the formation of DNA-adducts in the bronchial and alveolar epithelium and contributes to the development of lung cancer. Benz(a)pyrene and nitrosamine, typical carcinogens in cigarette smoke, undergo metabolic activation by the phase I enzymes, such as cytochrome P450 (CYP) 1A1, CYP2A6 and CYP2E1. The transcriptional regulation of these phase I enzymes is regulated by arylhydrocarbon receptor (AH-R) which binds many well-known carcinogens. To identify a cause and effect relationship, the expression of cytochrome CYP and AH-R in the bronchial epithelium was correlated with the history of cigarette smoking in patients with non-small cell lung carcinoma (NSCLC). Although CYP3A+ cells were absent in the bronchial epithelium of all patients, there were many CYP2E1+ cells in heavy (>1000 cigarette/day x year) smokers (38.5%). In contra-distinction, there was significantly less number of CYP2E1+ cells in light (less than 1000 cigarette/day x year) smokers (15.6%) or non-smokers (10.0%). Similarly, there were more CYP1A1+ (19.2%) and CYP2A6+ cells in heavy (65.4%) smokers as compared to non-smokers. The number of AH-R+ cells was also significantly higher in cases with p53 mutation (62.5%) than those without (12.2%) mutation. Since in patients with early NSCLC, CYP positivity showed a close correlation with a poor survival (p less than 0.01), expression of CYP in bronchial epithelium has a prognostic potential.

  17. Current smoking-specific gene expression signature in normal bronchial epithelium is enhanced in squamous cell lung cancer

    NARCIS (Netherlands)

    Boelens, Mirjam C.; van den Berg, Anke; Fehrmann, Rudolf S. N.; Geerlings, Marie; de Jong, Wouter K.; te Meerman, Gerard J; Sietsma, Hannie; Timens, Winn; Postma, Dirkje S.; Groen, Harry J. M.

    2009-01-01

    Cigarette smoking is the main risk factor for the development of squamous cell lung carcinoma (SCC). However, the smoking-related molecular changes in SCC have not been studied. Gene expression studies in both histologically normal bronchial epithelium and SCC epithelial samples identified genes dif

  18. Barrier disrupting effects of alternaria alternata extract on bronchial epithelium from asthmatic donors.

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    Marina S Leino

    Full Text Available Sensitization and exposure to the allergenic fungus Alternaria alternata has been associated with increased risk of asthma and asthma exacerbations. The first cells to encounter inhaled allergens are epithelial cells at the airway mucosal surface. Epithelial barrier function has previously been reported to be defective in asthma. This study investigated the contribution of proteases from Alternaria alternata on epithelial barrier function and inflammatory responses and compared responses of in vitro cultures of differentiated bronchial epithelial cells derived from severely asthmatic donors with those from non-asthmatic controls. Polarised 16HBE cells or air-liquid interface (ALI bronchial epithelial cultures from non-asthmatic or severe asthmatic donors were challenged apically with extracts of Alternaria and changes in inflammatory cytokine release and transepithelial electrical resistance (TER were measured. Protease activity in Alternaria extracts was characterised and the effect of selectively inhibiting protease activity on epithelial responses was examined using protease inhibitors and heat-treatment. In 16HBE cells, Alternaria extracts stimulated release of IL-8 and TNFα, with concomitant reduction in TER; these effects were prevented by heat-treatment of the extracts. Examination of the effects of protease inhibitors suggested that serine proteases were the predominant class of proteases mediating these effects. ALI cultures from asthmatic donors exhibited a reduced IL-8 response to Alternaria relative to those from healthy controls, while neither responded with increased thymic stromal lymphopoietin (TSLP release. Only cultures from asthmatic donors were susceptible to the barrier-weakening effects of Alternaria. Therefore, the bronchial epithelium of severely asthmatic individuals may be more susceptible to the deleterious effects of Alternaria.

  19. MicroRNA-221 modulates RSV replication in human bronchial epithelium by targeting NGF expression.

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    Sreekumar Othumpangat

    Full Text Available BACKGROUND: Early-life infection by respiratory syncytial virus (RSV is associated with aberrant expression of the prototypical neurotrophin nerve growth factor (NGF and its cognate receptors in human bronchial epithelium. However, the chain of events leading to this outcome, and its functional implications for the progression of the viral infection, has not been elucidated. This study sought to test the hypothesis that RSV infection modulates neurotrophic pathways in human airways by silencing the expression of specific microRNAs (miRNAs, and that this effect favors viral growth by interfering with programmed death of infected cells. METHODOLOGY: Human bronchial epithelial cells infected with green fluorescent protein-expressing RSV (rgRSV were screened with multiplex qPCR arrays, and miRNAs significantly affected by the virus were analyzed for homology with mRNAs encoding neurotrophic factors or receptors. Mimic sequences of selected miRNAs were transfected into non-infected bronchial cells to confirm the role of each of them in regulating neurotrophins expression at the gene and protein level, and to study their influence on cell cycle and viral replication. PRINCIPAL FINDINGS: RSV caused downregulation of 24 miRNAs and upregulation of 2 (p<0.01. Homology analysis of microarray data revealed that 6 of those miRNAs exhibited a high degree of complementarity to NGF and/or one of its cognate receptors TrKA and p75(NTR. Among the selected miRNAs, miR-221 was significantly downregulated by RSV and its transfection in bronchial epithelial cells maximally inhibited gene and protein expression of NGF and TrKA, increased apoptotic cell death, and reduced viral replication and infectivity. CONCLUSIONS/SIGNIFICANCE: Our data suggest that RSV upregulates the NGF-TrKA axis in human airways by silencing miR-221 expression, and this favors viral replication by interfering with the apoptotic death of infected cells. Consequently, the targeted delivery of

  20. Correspondence regarding "Effect of active smoking on the human bronchial epithelium transcriptome"

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    Zuyderduyn Scott D

    2009-02-01

    Full Text Available Abstract Background In the work of Chari et al. entitled "Effect of active smoking on the human bronchial epithelium transcriptome" the authors use SAGE to identify candidate gene expression changes in bronchial brushings from never, former, and current smokers. These gene expression changes are categorized into those that are reversible or irreversible upon smoking cessation. A subset of these identified genes is validated on an independent cohort using RT-PCR. The authors conclude that their results support the notion of gene expression changes in the lungs of smokers which persist even after an individual has quit. Results This correspondence raises questions about the validity of the approach used by the authors to analyze their data. The majority of the reported results suffer deficiencies due to the methods used. The most fundamental of these are explained in detail: biases introduced during data processing, lack of correction for multiple testing, and an incorrect use of clustering for gene discovery. A randomly generated "null" dataset is used to show the consequences of these shortcomings. Conclusion Most of Chari et al.'s findings are consistent with what would be expected by chance alone. Although there is clear evidence of reversible changes in gene expression, the majority of those identified appear to be false positives. However, contrary to the authors' claims, no irreversible changes were identified. There is a broad consensus that genetic change due to smoking persists once an individual has quit smoking; unfortunately, this study lacks sufficient scientific rigour to support or refute this hypothesis or identify any specific candidate genes. The pitfalls of large-scale analysis, as exemplified here, may not be unique to Chari et al.

  1. Absence of Fungal Spore Internalization by Bronchial Epithelium in Mouse Models Evidenced by a New Bioimaging Approach and Transmission Electronic Microscopy.

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    Rammaert, Blandine; Jouvion, Grégory; de Chaumont, Fabrice; Garcia-Hermoso, Dea; Szczepaniak, Claire; Renaudat, Charlotte; Olivo-Marin, Jean-Christophe; Chrétien, Fabrice; Dromer, Françoise; Bretagne, Stéphane

    2015-09-01

    Clinical data and experimental studies suggest that bronchial epithelium could serve as a portal of entry for invasive fungal infections. We therefore analyzed the interactions between molds and the bronchial/bronchiolar epithelium at the early steps after inhalation. We developed invasive aspergillosis (Aspergillus fumigatus) and mucormycosis (Lichtheimia corymbifera) murine models that mimic the main clinical risk factors for these infections. Histopathology studies were completed with a specific computer-assisted morphometric method to quantify bronchial and alveolar spores and with transmission electron microscopy. Morphometric analysis revealed a higher number of bronchial/bronchiolar spores for A. fumigatus than L. corymbifera. The bronchial/bronchiolar spores decreased between 1 and 18 hours after inoculation for both fungi, except in corticosteroid-treated mice infected with A. fumigatus, suggesting an effect of cortisone on bronchial spore clearance. No increase in the number of spores of any species was observed over time at the basal pole of the epithelium, suggesting the lack of transepithelial crossing. Transmission electron microscopy did not show spore internalization by bronchial epithelial cells. Instead, spores were phagocytized by mononuclear cells on the apical pole of epithelial cells. Early epithelial internalization of fungal spores in vivo cannot explain the bronchial/bronchiolar epithelium invasion observed in some invasive mold infections. The bioimaging approach provides a useful means to accurately enumerate and localize the fungal spores in the pulmonary tissues.

  2. Tracheal dysplasia precedes bronchial dysplasia in mouse model of N-nitroso trischloroethylurea induced squamous cell lung cancer.

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    Moumita Ghosh

    Full Text Available Squamous cell lung cancer (SCC is the second leading cause of lung cancer death in the US and has a 5-year survival rate of only 16%. Histological changes in the bronchial epithelium termed dysplasia are precursors to invasive SCC. However, the cellular mechanisms that cause dysplasia are unknown. To fill this knowledge gap, we used topical application of N-nitroso-tris chloroethylurea (NTCU for 32 weeks to induce squamous dysplasia and SCC in mice. At 32 weeks the predominant cell type in the dysplastic airways was Keratin (K 5 and K14 expressing basal cells. Notably, basal cells are extremely rare in the normal mouse bronchial epithelium but are abundant in the trachea. We therefore evaluated time-dependent changes in tracheal and bronchial histopathology after NTCU exposure (4, 8, 12, 16, 25 and 32 weeks. We show that tracheal dysplasia occurs significantly earlier than that of the bronchial epithelium (12 weeks vs. 25 weeks. This was associated with increased numbers of K5+/K14+ tracheal basal cells and a complete loss of secretory (Club cell secretory protein expressing CCSP+ and ciliated cells. TUNEL staining of NTCU treated tissues confirmed that the loss of CCSP+ and ciliated cells was not due to apoptosis. However, mitotic index (measured by bromodeoxyuridine incorporation showed that NTCU treatment increased proliferation of K5+ basal cells in the trachea, and altered bronchial mitotic population from CCSP+ to K5+ basal cells. Thus, we demonstrate that NTCU-induced lung epithelial dysplasia starts in the tracheal epithelium, and is followed by basal cell metaplasia of the bronchial epithelium. This analysis extends our knowledge of the NTCU-SCC model by defining the early changes in epithelial cell phenotypes in distinct airway locations, and this may assist in identifying new targets for future chemoprevention studies.

  3. Rhinovirus infection induces cytotoxicity and delays wound healing in bronchial epithelial cells

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    Constantopoulos Andreas G

    2005-10-01

    Full Text Available Abstract Background Human rhinoviruses (RV, the most common triggers of acute asthma exacerbations, are considered not cytotoxic to the bronchial epithelium. Recent observations, however, have questioned this knowledge. The aim of this study was to evaluate the ability of RV to induce epithelial cytotoxicity and affect epithelial repair in-vitro. Methods Monolayers of BEAS-2B bronchial epithelial cells, seeded at different densities were exposed to RV serotypes 1b, 5, 7, 9, 14, 16. Cytotoxicity was assessed chromatometrically. Epithelial monolayers were mechanically wounded, exposed or not to RV and the repopulation of the damaged area was assessed by image analysis. Finally epithelial cell proliferation was assessed by quantitation of proliferating cell nuclear antigen (PCNA by flow cytometry. Results RV1b, RV5, RV7, RV14 and RV16 were able to induce considerable epithelial cytotoxicity, more pronounced in less dense cultures, in a cell-density and dose-dependent manner. RV9 was not cytotoxic. Furthermore, RV infection diminished the self-repair capacity of bronchial epithelial cells and reduced cell proliferation. Conclusion RV-induced epithelial cytotoxicity may become considerable in already compromised epithelium, such as in the case of asthma. The RV-induced impairment on epithelial proliferation and self-repair capacity may contribute to the development of airway remodeling.

  4. Virus Infection-Induced Bronchial Asthma Exacerbation

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    Mutsuo Yamaya

    2012-01-01

    Full Text Available Infection with respiratory viruses, including rhinoviruses, influenza virus, and respiratory syncytial virus, exacerbates asthma, which is associated with processes such as airway inflammation, airway hyperresponsiveness, and mucus hypersecretion. In patients with viral infections and with infection-induced asthma exacerbation, inflammatory mediators and substances, including interleukins (ILs, leukotrienes and histamine, have been identified in the airway secretions, serum, plasma, and urine. Viral infections induce an accumulation of inflammatory cells in the airway mucosa and submucosa, including neutrophils, lymphocytes and eosinophils. Viral infections also enhance the production of inflammatory mediators and substances in airway epithelial cells, mast cells, and other inflammatory cells, such as IL-1, IL-6, IL-8, GM-CSF, RANTES, histamine, and intercellular adhesion molecule-1. Viral infections affect the barrier function of the airway epithelial cells and vascular endothelial cells. Recent reports have demonstrated augmented viral production mediated by an impaired interferon response in the airway epithelial cells of asthma patients. Several drugs used for the treatment of bronchial asthma reduce viral and pro-inflammatory cytokine release from airway epithelial cells infected with viruses. Here, I review the literature on the pathogenesis of the viral infection-induced exacerbation of asthma and on the modulation of viral infection-induced airway inflammation.

  5. Effects of irritant gas induced damage of bronchial epithelium (SO sub 2 , NO sub 2 , ozone, cigarette smoke) on sensitization by inhaled allergens. Lokale bronchiale Sensibilisierung mit inhalativen Antigenen nach vorausgegangener Schaedigung durch Reizgasinhalation (SO sub 2 , NO sub 2 , Ozon und Tabakrauch)

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    Riedel, F.; Rieger, C.H.L. (Marburg Univ. (Germany, F.R.). Zentrum fuer Kinderheilkunde)

    1989-04-01

    This report concerns results of ozone- and tobacco smoke exposure: 5 days of exposure (6 hours per day) with 1.0 ppm O{sub 3}, but not with 0.5 ppm O{sub 3}, enhance bronchial sensitization compared to an air-exposed control group. The combination of 1.0 ppm SO{sub 2} (not effective on its own) with 0.5 ppm O{sub 3} has the same effect. Exposure with tobacco smoke (mixture of main- and sidestream smoke), leading to serum Cotinine levels of 87 ng/ml in the mean at the end of the 5th exposure day, enhances sensitization to inhaled Ovalbumin as well. During a 5-day exposure with 5 ppm SO{sub 2} groups of 6 animals were treated prophylactically with anti-inflammatory drugs and the influence on the sensitization by inhaled Ovalbumin was studied. Inhalation of Nedocromil-Sodium and high-dose oral Methylprednisolone (8 mg/kg/d) could completely inhibit inhalative sensitization. Indomethacin was only partly effective, whereas no effect was seen on treatment with low-dose steroids and PAF-antagonist WEB 2170 BS. Inflammatory reactions as the leading pathogenetic mechanism of air pollution induced inhalative sensitization is discussed. (orig./MG).

  6. IL-13 induces a bronchial epithelial phenotype that is profibrotic

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    Dinh Bao T

    2008-03-01

    Full Text Available Abstract Background Inflammatory cytokines (e.g. IL-13 and mechanical perturbations (e.g. scrape injury to the epithelium release profibrotic factors such as TGF-β2, which may, in turn, stimulate subepithelial fibrosis in asthma. We hypothesized that prolonged IL-13 exposure creates a plastic epithelial phenotype that is profibrotic through continuous secretion of soluble mediators at levels that stimulate subepithelial fibrosis. Methods Normal human bronchial epithelial cells (NHBE were treated with IL-13 (0, 0.1, 1, or 10 ng/ml for 14 days (day 7 to day 21 following seeding at an air-liquid interface during differentiation, and then withdrawn for 1 or 7 days. Pre-treated and untreated NHBE were co-cultured for 3 days with normal human lung fibroblasts (NHLF embedded in rat-tail collagen gels during days 22–25 or days 28–31. Results IL-13 induced increasing levels of MUC5AC protein, and TGF-β2, while decreasing β-Tubulin IV at day 22 and 28 in the NHBE. TGF-β2, soluble collagen in the media, salt soluble collagen in the matrix, and second harmonic generation (SHG signal from fibrillar collagen in the matrix were elevated in the IL-13 pre-treated NHBE co-cultures at day 25, but not at day 31. A TGF-β2 neutralizing antibody reversed the increase in collagen content and SHG signal. Conclusion Prolonged IL-13 exposure followed by withdrawal creates an epithelial phenotype, which continuously secretes TGF-β2 at levels that increase collagen secretion and alters the bulk optical properties of an underlying fibroblast-embedded collagen matrix. Extended withdrawal of IL-13 from the epithelium followed by co-culture does not stimulate fibrosis, indicating plasticity of the cultured airway epithelium and an ability to return to a baseline. Hence, IL-13 may contribute to subepithelial fibrosis in asthma by stimulating biologically significant TGF-β2 secretion from the airway epithelium.

  7. Epithelium

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    The term "epithelium" refers to layers of cells that line hollow organs and glands. It is also those cells that make ... Epithelium. In: Kierszenbaum AL, Tres LL. Histology and Cell Biology - An Introduction to Pathology , 3rd ed. Philadelphia, ...

  8. Benzalkonium Chloride Induced Bronchoconstriction in Patients with Stable Bronchial Asthma

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    Lee, Byoung Hoon

    2007-01-01

    Background Although benzalkonium chloride (BAC)-induced bronchoconstriction occurs in patients with bronchial asthma, BAC-containing nebulizer solutions are still being used in daily practice in Korea. The aim of this study was to evaluate the effects of inhaled aqueous solutions containing BAC. Methods Thirty subjects with bronchial asthma and 10 normal controls inhaled up to three 600 µg nebulized doses of BAC using a jet nebulizer. FEV1 (forced expiratory volume at one second) was measured 15 minutes after each dose. Inhalations were repeated every 20 minutes until FEV1 decreased by 15% or more (defined as BAC-induced bronchoconstriction) or the 3 doses were administered. Results The percent fall in FEV1 in response to BAC inhalation was significantly higher in asthmatics than in normal subjects (p<0.05). BAC administration in subjects with asthma reached a plateau (maximal effect). BAC-induced bronchoconstriction was found in 6 asthmatics (20%), with two responders after the 2nd inhalation and after the 3rd inhalation. The percent fall in FEV1 in response to the 1st inhalation of BAC was significantly higher in asthmatics with higher bronchial hyperresponsiveness (BHR) than in those with lower BHR. Conclusions This study suggests that the available multi-dose nebulized solution is generally safe. However, significant bronchoconstriction can occur at a relatively low BAC dose in asthmatics with severe airway responsiveness. PMID:18309682

  9. Activation of MTOR in pulmonary epithelium promotes LPS-induced acute lung injury.

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    Hu, Yue; Lou, Jian; Mao, Yuan-Yuan; Lai, Tian-Wen; Liu, Li-Yao; Zhu, Chen; Zhang, Chao; Liu, Juan; Li, Yu-Yan; Zhang, Fan; Li, Wen; Ying, Song-Min; Chen, Zhi-Hua; Shen, Hua-Hao

    2016-12-01

    MTOR (mechanistic target of rapamycin [serine/threonine kinase]) plays a crucial role in many major cellular processes including metabolism, proliferation and macroautophagy/autophagy induction, and is also implicated in a growing number of proliferative and metabolic diseases. Both MTOR and autophagy have been suggested to be involved in lung disorders, however, little is known about the role of MTOR and autophagy in pulmonary epithelium in the context of acute lung injury (ALI). In the present study, we observed that lipopolysaccharide (LPS) stimulation induced MTOR phosphorylation and decreased the expression of MAP1LC3B/LC3B (microtubule-associated protein 1 light chain 3 β)-II, a hallmark of autophagy, in mouse lung epithelium and in human bronchial epithelial (HBE) cells. The activation of MTOR in HBE cells was mediated by TLR4 (toll-like receptor 4) signaling. Genetic knockdown of MTOR or overexpression of autophagy-related proteins significantly attenuated, whereas inhibition of autophagy further augmented, LPS-induced expression of IL6 (interleukin 6) and IL8, through NFKB signaling in HBE cells. Mice with specific knockdown of Mtor in bronchial or alveolar epithelial cells exhibited significantly attenuated airway inflammation, barrier disruption, and lung edema, and displayed prolonged survival in response to LPS exposure. Taken together, our results demonstrate that activation of MTOR in the epithelium promotes LPS-induced ALI, likely through downregulation of autophagy and the subsequent activation of NFKB. Thus, inhibition of MTOR in pulmonary epithelial cells may represent a novel therapeutic strategy for preventing ALI induced by certain bacteria.

  10. Asthma Bronchiale and Exercise-Induced Bronchoconstriction.

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    Jayasinghe, Harshani; Kopsaftis, Zoe; Carson, Kristin

    2015-01-01

    Exercising regularly has a wide range of beneficial health effects; in particular, it has been well documented to help in the management of chronic illnesses including asthma. However, in some individuals, exertion can also trigger an exacerbation of asthmatic episodes and subsequent acute attacks of breathlessness, coughing, tightness of the chest and wheezing. This physiological process is called exercise-induced bronchoconstriction (EIB) whereby post-exercise forced expiratory volume in 1 s is reduced by 10-15% from baseline. While EIB is highly prevalent in asthmatics and presents with similar respiratory symptoms, asthma and EIB are not mutually exclusive. The aim of this review is to present a broad overview of both conditions in order to enhance the understanding of the similarities and differences distinguishing them as two separate entities. The pathophysiology and mechanisms underlying asthma are well described with research now focussing on defining phenotypes for targeted management strategies. Conversely, the mechanistic understanding of EIB remains largely under-described. Diagnostic pathways for both are established and similar, as are pharmacologic and non-pharmacologic treatments and management approaches, which have enhanced success with early detection. Given the potential for exacerbation of asthma, exercise avoidance is common but counterproductive as current evidence indicates that it is well tolerated and improves quality of life. Literature supporting the benefit of exercise for EIB sufferers is at present favourable, yet extremely limited; therefore, future research should be directed in this area as well as towards further developing the understanding of the pathophysiology and mechanisms underpinning both EIB and asthma.

  11. 中药火把花根对油酸致急性肺损伤大鼠 气道紧密连接蛋白表达的影响%Effects of traditional Chinese medicine colquhounia root tablet on the expression of tight junction protein ;claudin-2 and ZO-1 in bronchial epithelium tissue of rats with acute lung injury induced by oleic acid

    Institute of Scientific and Technical Information of China (English)

    邵萍; 李学莉; 朱金源; 丁欢; 马希刚; 曹相原

    2016-01-01

    including cellular edema and structural disorder of intercellular connection by optical microscope, and LIS, W/D ratio, and LPI were significantly increased (LIS: 3.81±0.42 vs. 0.40±0.08, W/D: 7.68±0.64 vs. 4.44±0.39, LPI: 0.89±0.15 vs. 0.38±0.05, all P < 0.01). Claudin-2 and ZO-1 were mainly expressed in the bronchial epithelium cell, and the expression degrees were significantly weakened in ALI group as compared with control group. It was shown by Western Blot results that compared with control group, the protein expressions of claudin-2 and ZO-1 were significantly down-regulated in ALI group [claudin-2 protein (gray value): 0.43±0.31 vs. 2.16±1.33, ZO-1 protein (gray value): 1.25±0.41 vs. 2.82±0.76, both P < 0.01]. Compared with ALI group, colquhounia root pretreatment could effectively diminish the degree of ALI (LIS: 1.22±0.39 vs. 3.81±0.42, W/D: 4.62±0.84 vs. 7.68±0.64, LPI: 0.46±0.07 vs. 0.89±0.15, all P < 0.01), and the protein expressions of claudin-2 and ZO-1 were significantly up-regulated [claudin-2 protein (gray value): 2.98±0.91 vs. 0.43±0.31, ZO-1 protein (gray value): 2.35±0.51 vs. 1.25±0.41, both P < 0.01]. Conclusion Administration of colquhounia root table could attenuate lung injury induced by oleic acid with improving epithelial barrier function via up-regulate the expression claudin-2 and ZO-1, which play a protective effect on the lung of rats with ALI.

  12. Tungsten-induced carcinogenesis in human bronchial epithelial cells

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    Laulicht, Freda; Brocato, Jason; Cartularo, Laura; Vaughan, Joshua; Wu, Feng; Kluz, Thomas; Sun, Hong; Oksuz, Betul Akgol; Shen, Steven; Paena, Massimilano; Medici, Serenella; Zoroddu, Maria Antonietta; Costa, Max

    2015-01-01

    Metals such as arsenic, cadmium, beryllium, and nickel are known human carcinogens; however, other transition metals, such as tungsten (W), remain relatively uninvestigated with regard to their potential carcinogenic activity. Tungsten production for industrial and military applications has almost doubled over the past decade and continues to increase. Here, for the first time, we demonstrate tungsten’s ability to induce carcinogenic related endpoints including cell transformation, increased migration, xenograft growth in nude mice, and the activation of multiple cancer related pathways in transformed clones as determined by RNA seq. Human bronchial epithelial cell line (Beas-2B) exposed to tungsten developed carcinogenic properties. In a soft agar assay, tungsten-treated cells formed more colonies than controls and the tungsten-transformed clones formed tumors in nude mice. RNA-sequencing data revealed that the tungsten-transformed clones altered the expression of many cancer-associated genes when compared to control clones. Genes involved in lung cancer, leukemia, and general cancer genes were deregulated by tungsten. Taken together, our data shows the carcinogenic potential of tungsten. Further tests are needed, including in vivo and human studies, in order to validate tungsten as a carcinogen to humans. PMID:26164860

  13. Captopril augments acetylcholine-induced bronchial smooth muscle contractions in vitro via kinin-dependent mechanisms.

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    Agrawal, Naman; Akella, Aparna; Deshpande, Shripad B

    2016-06-01

    Angiotensin converting enzyme (ACE) inhibitors therapy is aassociated with bothersome dry cough as an adverse effect. The mechanisms underlying this adverse effect are not clear. Therefore, influence of captopril (an ACE inhibitor) on acetylcholine (ACh)-induced bronchial smooth muscle contractions was investigated. Further, the mechanisms underlying the captopril-induced changes were also explored. In vitro contractions of rat bronchial smooth muscle to cumulative concentrations of ACh were recorded before and after exposure to captopril. Further, the involvement of kinin and inositol triphosphate (IP₃) pathways for captopril-induced alterations were explored. ACh produced concentration-dependent (5-500 µM) increase in bronchial smooth muscle contractions. Pre-treatment with captopril augmented the ACh-induced contractions at each concentration significantly. Pre-treatment with aprotinin (kinin synthesis inhibitor) or heparin (inositol triphosphate, IP₃-inhibitor), blocked the captopril-induced augmentation of bronchial smooth muscle contractions evoked by ACh. Further, captopril-induced augmentation was absent in calcium-free medium. These results suggest that captopril sensitizes bronchial smooth muscles to ACh-induced contractions. This sensitization may be responsible for dry cough associated with captopril therapy.

  14. On the value of certain genotypic properties for forming exercise-induced bronchial asthma in children

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    Лорина Алімівна Іванова

    2015-10-01

    Full Text Available Introduction. Exercise-induced bronchial asthma is a separate phenotype of bronchial asthma (BA that defines an exercise-associated transitory obstruction of bronchial tubes, especially decrease of the forced expiration volume for 1 sec. (FEV1 by 10 % and more of an output quantity after the relevant bronchial provocation test. At the same time there is not sufficient elucidation of the role of genetic component especially GSTT1 і GSTM1 gene deletions and\\or mutational polymorphism of еNOS gene in development of exercise-induced bronchial asthma in children.Aim. To study the value of deletion (GSTT1 and GSTM1 genes and mutational (еNOS gene polymorphism in formation of bronchial tubes lability in children with exercise-induced bronchial asthma to optimize individual medioprophylactic recommendations.Materials and methods. During the study there were examined 102 school-aged children with BA in pulmo-allergology department of RSCH in Chernovtsy. To verify the exercise-induced bronchial asthma (EIBA there was studied an exercise tolerance of patients and their bronchial tubes lability in the response to the dosed run and bronchomotor test with inhalation with 200 mkg of salbutamol. And the received results were represented as a bronchial tubes lability indicator (BTLI, % and its components – bronchospasm index (BSI, % and bronchodilation index (BDI, %. 2 clinical groups were formed in examination of children. The first (I, main included 50 schoolchildren with EIBA and the comparative one (II group – 52 children with BA without the signs of exercise-induced bronchospasm (EIBS. Results of research. There was established that the “null” genotype of aforesaid genes is three times more often (10,0 % against 3,85 %, P<0,05in children with exercise-induced bronchial asthma and mutations of еNOS gene ( GT, ТТ genotype take place in every second children. There was detected that the highest bronchospasm indicators are in patients with GSTT1

  15. Protective effect of sodium cromoglycate on lipopolysaccharide-induced bronchial obstruction in asthmatics.

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    Michel, O; Ginanni, R; Sergysels, R

    1995-11-01

    Lipopolysaccharides (LPS, the major part of endotoxins) are bacterial proinflammatory substances which can induce in asthmatic patients after inhalation a bronchial obstruction with an increase in both histamine bronchial hyperresponsiveness and blood inflammatory markers. The aim of the present study was to evaluate whether an acute inhalation of sodium cromoglycate, an anti-inflammatory and membrane-stabilizating agent, can block the LPS-induced lung function response. Using a double-blind placebo-controlled crossover method, 7 asthmatic subjects were submitted, at 4 days' interval, to a bronchial challenge test with either solvent solution or LPS (20 micrograms) preceded by inhalation of sodium cromoglycate (10 mg) or placebo. Compared to the solvent reaction, LPS induced a significant bronchial obstruction [measured by both the forced expiratory volume in 1 s (FEV1) and the airway resistances] beginning at the 60th minute and lasting more than 300 min (p sodium cromoglycate significantly inhibited the LPS-induced bronchial obstruction. The total lung capacity did not change significantly after LPS inhalation. Thus, this study showed that in asthmatics the LPS-induced FEV1 response is blocked by acute treatment with sodium cromoglycate. Sodium cromoglycate could be an active treatment in asthmatics exposed to house dust containing endotoxin.

  16. The Effect of Therapeutic Blockades of Dust Particles-Induced Ca2+ Signaling and Proinflammatory Cytokine IL-8 in Human Bronchial Epithelial Cells

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    Ju Hee Yoon

    2015-01-01

    Full Text Available Bronchial epithelial cells are the first barrier of defense against respiratory pathogens. Dust particles as extracellular stimuli are associated with inflammatory reactions after inhalation. It has been reported that dust particles induce intracellular Ca2+ signal, which subsequently increases cytokines production such as interleukin- (IL- 8. However, the study of therapeutic blockades of Ca2+ signaling induced by dust particles in human bronchial epithelial cells is poorly understood. We investigated how to modulate dust particles-induced Ca2+ signaling and proinflammatory cytokine IL-8 expression. Bronchial epithelial BEAS-2B cells were exposed to PM10 dust particles and subsequent mediated intracellular Ca2+ signaling and reactive oxygen species signal. Our results show that exposure to several inhibitors of Ca2+ pathway attenuated the PM10-induced Ca2+ response and subsequent IL-8 mRNA expression. PM10-mediated Ca2+ signal and IL-8 expression were attenuated by several pharmacological blockades such as antioxidants, IP3-PLC blockers, and TRPM2 inhibitors. Our results show that blockades of PLC or TRPM2 reduced both of PM10-mediated Ca2+ signal and IL-8 expression, suggesting that treatment with these blockades should be considered for potential therapeutic trials in pulmonary epithelium for inflammation caused by environmental events such as seasonal dust storm.

  17. Exercise-induced bronchoconstriction and non-specific airway hyperreactivity in patients suffering from bronchial asthma

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    Novković Dobrivoje

    2014-01-01

    Full Text Available Background/Aim. Physical activity is a common stimulus of asthmatic symptoms manifestation. Airway hyperreactivity is a predisposing cause of exercise induced bronchial obstruction, diagnosed by histamine inhalation. The aim of this study was to determine the relation between the amounts of histamine needed to induce non-specific airway hyperreactivity and exercise-induced bronchial obstruction. Methods. This randomized cross-over study included 160 male patients (age 19-27 years suffering from bronchial asthma who showed positive results as the reaction after the histamine bronchial provocation test. Histamine concentrations were in a range of 0.03 to 4 mg/mL. Each patient participated in the exercise stress test conducted on a conveyor belt. The results of the exercise stress test were considered positive if the FEV1 level dropped by at least 15% from its initial value, 5-10 minutes after the test. Results. All the patients showed positive results as the reaction after the histamine bronchial provocation test, while 50 of them showed positive results after the exercise-induced stress test. There was a statistically highly significant difference in administrated histamine concentrations between the group of patients that had positive results on exercise stress test and those who did not (1mg/mL vs 0.5mg/mL; U = 1678; p < 0.01. Also, there was a statistically significant difference concerning the frequency of the positive results regarding histamine concentration after induced stress test (χ2 = 10.885; p = 0.001. Among the patients with positive results, there was a statistically highly significant number of patients with bronchial obstruction induced by less than 2 mg/mL of histamine (p < 0.01. A statistically significant relation between the amount of histamine needed to induce bronchial obstruction and the results of the exercise stress test (p < 0.01 was also observed after the testing. Conclusion. In the group of patients with positive

  18. Prevention of Antigen-Induced Bronchial Hyperreactivity and Airway Inflammation in Sensitized Guinea-Pigs by Tacrolimus

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    J. R. Lapa e Silva

    1999-01-01

    Full Text Available We examined the effect of the immunosuppressive agent, tacrolimus (FK506, on antigen-induced bronchial hyperreactivity to acetylcholine and leukocyte infiltration into the airways of ovalbumin-challenged guinea-pigs. Subcutaneous injection of 0.5 mg/kg of FK506, 1 h before and 5 h after intra-nasal antigen challenge prevented bronchial hyperreactivity to aerosolized acetylcholine, eosinophilia in bronchoalveolar lavage (BAL fluid and bronchial tissue and the invasion of the bronchial wall by CD4+ T-lymphocytes. FK506 also suppressed ovalbumininduced increase in the number of leukocytes adhering to the pulmonary vascular endothelium and expressing α4-integrins. Inhibition by FK506 of antigen-induced bronchial hyperreactivity in sensitized guinea-pigs may thus relate to its ability to prevent the emergence of important inflammatory components of airway inflammation, such as eosinophil accumulation, as well as CD4+ T-lymphocyte infiltration into the bronchial tissue.

  19. Pathogenesis and management of virus infection-induced exacerbation of senile bronchial asthma and chronic pulmonary emphysema.

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    Yamaya, Metstuo

    2002-06-01

    The number of senile patients with therapy resistant bronchial asthma, chronic pulmonary emphysema increases due to the habit of smoking and increased number of older people, and these inflammatory pulmonary diseases are the leading causes of death worldwide. Rhinoviruses cause the majority of common colds, and provoke exacerbations of bronchial asthma and chronic pulmonary emphysema. Here, I review the pathogenesis and management of rhinovirus infection-induced exacerbation of senile bronchial asthma and chronic pulmonary emphysema.

  20. Intestinal ischemia/reperfusion induces bronchial hyperreactivity and increases serum TNF-alpha in rats

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    Arruda Marcio Jose Cristiano de

    2006-01-01

    Full Text Available INTRODUCTION: Intestinal or hepatic ischemia/reperfusion induces acute lung injury in animal models of multiple organ failure. Tumor necrosis factor (TNF- alpha is involved in the underlying inflammatory mechanism of acute respiratory distress syndrome. Although the inflammatory cascade leading to acute respiratory distress syndrome has been extensively investigated, the mechanical components of acute respiratory distress syndrome are not fully understood. Our hypothesis is that splanchnic ischemia/reperfusion increases airway reactivity and serum TNF-alpha levels. OBJECTIVE: To assess bronchial smooth muscle reactivity under methacholine stimulation, and to measure serum TNF-alpha levels following intestinal and/or hepatic ischemia/reperfusion in rats. METHOD: Rats were subjected to 45 minutes of intestinal ischemia, or 20 minutes of hepatic ischemia, or to both (double ischemia, or sham procedures (control, followed by 120 minutes of reperfusion. The animals were then sacrificed, and the bronchial response to increasing methacholine molar concentrations (10-7 to 3 x 10-4 was evaluated in an ex-vivo bronchial muscle preparation. Serum TNF-alpha was determined by the L929-cell bioassay. RESULTS: Bronchial response (g/100 mg tissue showed increased reactivity to increasing methacholine concentrations in the intestinal ischemia and double ischemia groups, but not in the hepatic ischemia group. Similarly, serum TNF-alpha (pg/mL concentration was increased in the intestinal ischemia and double ischemia groups, but not in the hepatic ischemia group. CONCLUSION: Intestinal ischemia, either isolated or associated with hepatic ischemia, increased bronchial smooth muscle reactivity, suggesting a possible role for bronchial constriction in respiratory dysfunction following splanchnic ischemia/reperfusion. This increase occurred in concomitance with serum TNF-alpha increase, but whether the increase in TNF-alpha caused this bronchial contractility remains

  1. Oxidative stress induced Interleukin-32 mRNA expression in human bronchial epithelial cells

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    Kudo Megumi

    2012-03-01

    Full Text Available Abstract Background Chronic obstructive pulmonary disease (COPD is characterized by airflow obstruction and persistent inflammation in the airways and lung parenchyma. Oxidative stress contributes to the pathogenesis of COPD. Interleukin (IL-32 expression has been reported to increase in the lung tissue of patients with COPD. Here, we show that IFNγ upregulated IL-32 expression and that oxidative stress augmented IFNγ-induced-IL-32 expression in airway epithelial cells. We further investigated transcriptional regulation responsible for IFNγ induced IL-32 expression in human airway epithelial cells. Methods Human bronchial epithelial (HBE cells were stimulated with H2O2 and IFNγ, and IL-32 expression was evaluated. The cell viability was confirmed by MTT assay. The intracellular signaling pathways regulating IL-32 expression were investigated by examining the regulatory effects of MAPK inhibitors and JAK inhibitor after treatment with H2O2 and IFNγ, and by using a ChIP assay to identify transcription factors (i.e. c-Jun, CREB binding to the IL-32 promoter. Promoter activity assays were conducted after mutations were introduced into binding sites of c-Jun and CREB in the IL-32 promoter. IL-32 expression was also examined in HBE cells in which the expression of either c-Jun or CREB was knocked out by siRNA of indicated transcription factors. Results There were no significant differences of cell viability among groups. After stimulation with H2O2 or IFNγ for 48 hours, IL-32 expression in HBE cells was increased by IFNγ and synergistically upregulated by the addition of H2O2. The H2O2 augmented IFNγ induced IL-32 mRNA expression was suppressed by a JNK inhibitor, but not by MEK inhibitor, p38 inhibitor, and JAK inhibitor I. Significant binding of c-Jun and CREB to the IL-32 promoter was observed in the IFNγ + H2O2 stimulated HBE cells. Introducing mutations into the c-Jun/CREB binding sites in the IL-32 promoter prominently suppressed its

  2. Enhancement of Methacholine-Evoked Tracheal Contraction Induced by Bacterial Lipopolysaccharides Depends on Epithelium and Tumor Necrosis Factor

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    T. Secher

    2012-01-01

    Full Text Available Inhaled bacterial lipopolysaccharides (LPSs induce an acute tumour necrosis factor-alpha (TNF-α- dependent inflammatory response in the murine airways mediated by Toll-like receptor 4 (TLR4 via the myeloid differentiation MyD88 adaptor protein pathway. However, the contractile response of the bronchial smooth muscle and the role of endogenous TNFα in this process have been elusive. We determined the in vivo respiratory pattern of C57BL/6 mice after intranasal LPS administration with or without the presence of increasing doses of methacholine (MCh. We found that LPS administration altered the basal and MCh-evoked respiratory pattern that peaked at 90 min and decreased thereafter in the next 48 h, reaching basal levels 7 days later. We investigated in controlled ex vivo condition the isometric contraction of isolated tracheal rings in response to MCh cholinergic stimulation. We observed that preincubation of the tracheal rings with LPS for 90 min enhanced the subsequent MCh-induced contractile response (hyperreactivity, which was prevented by prior neutralization of TNFα with a specific antibody. Furthermore, hyperreactivity induced by LPS depended on an intact epithelium, whereas hyperreactivity induced by TNFα was well maintained in the absence of epithelium. Finally, the enhanced contractile response to MCh induced by LPS when compared with control mice was not observed in tracheal rings from TLR4- or TNF- or TNF-receptor-deficient mice. We conclude that bacterial endotoxin-mediated hyperreactivity of isolated tracheal rings to MCh depends upon TLR4 integrity that signals the activation of epithelium, which release endogenous TNFα.

  3. Recurrence of squamous cell lung carcinoma is associated with the co-presence of reactive lesions in tumor-adjacent bronchial epithelium.

    Science.gov (United States)

    Pankova, Olga V; Denisov, Evgeny V; Ponomaryova, Anastasia A; Gerashchenko, Tatiana S; Tuzikov, Sergey A; Perelmuter, Vladimir M

    2016-03-01

    Recurrences occur in 30 % of lung cancer patients after radical therapy; however, known prognostic factors are not always effective. In this study, we investigated whether the frequency of squamous non-small cell lung cancer (NSCLC) recurrence depends on the presence of reactive lesions in tumor-adjacent bronchial epithelium. Specimens of adjacent lung tissue from 104 patients with squamous NSCLC were used for the determination of basal cell hyperplasia (BCH) and squamous metaplasia (SM) and for the analysis of the expression of Ki-67, p53, Bcl-2, and CD138. We found that recurrence was observed in 36.7 % of patients with BCH combined with SM (BCH + SM+) in the same bronchus, compared with 1.8 % in patients with isolated BCH (BCH + SM-; odds ratio (OR) 31.26, 95 % confidence interval (CI) 3.77-258.60; p = 0.00002). The percentage of Ki-67-positive cells was significantly higher in BCH + SM+ than in BCH + SM- (34.9 vs. 18.3 %; effect size 2.86, 95 % CI 2.23-3.47; p = 0.003). P53 expression was also more significant in BCH + SM+ than in BCH + SM- (14.4 vs. 9.6 %; effect size 1.22, 95 % CI 0.69-1.76; p = 0.0008). In contrast, CD138 expression was lower in BCH + SM+ than in BCH + SM- (21.8 vs. 38.5 %; effect size -6.26, 95 % CI -7.31 to -5.22; p = 0.003). Based on our results, we concluded that the co-presence of reactive bronchial lesions is associated with the development of recurrent squamous NSCLC and may be a negative prognostic indicator. In addition, significant differences in Ki-67, p53, and CD138 expression exist between isolated BCH and BCH combined with SM that probably reflect part of biological differences, which could relate to the mechanism of lung cancer recurrence.

  4. Effects of budesonide on P38 MAPK activation, apoptosis and IL-8 secretion, induced by TNF-alpha and Haemophilus influenzae in human bronchial epithelial cells.

    Science.gov (United States)

    Gallelli, L; Pelaia, G; Fratto, D; Muto, V; Falcone, D; Vatrella, A; Curto, L S; Renda, T; Busceti, M T; Liberto, M C; Savino, R; Cazzola, M; Marsico, S A; Maselli, R

    2010-01-01

    Non-typeable Haemophilus influenzae (NTHi) is one of the most frequently involved pathogens in bacterial exacerbations of chronic obstructive pulmonary disease (COPD). In the airways, the main tissue target of NTHi is bronchial epithelium, where this pathogen can further amplify the inflammatory and structural changes induced by proinflammatory cytokines such as tumour necrosis factor-alpha (TNF-alpha). Therefore, the aim of this study is to investigate, in primary cultures of human bronchial epithelial cells, the effects of NTHi on signal transduction pathways, apoptotic events and chemokine production activated by TNF-alpha. Moreover, we also evaluated the effects exerted on such cellular and molecular phenomena by a corticosteroid drug. p38 mitogen-activated protein kinase (MAPK) phosphorylation was analyzed by Western blotting, using an anti-phospho-p38 MAPK monoclonal antibody. Apoptosis was assayed by active caspase-3 expression. Interleukin-8 (IL-8/CXCL8) was detected in cell-free culture supernatants by ELISA. TNF-alpha induced a significant increase in p38 MAPK phosphorylation. NTHi was able to potentiate the stimulatory actions of TNF-alpha on caspase-3 expression and, to a lesser extent, on IL-8 secretion. These effects were significantly (P less than 0.01) inhibited by a pharmacological pre-treatment with budesonide. These results suggest that TNF-alpha is able to stimulate, via activation of p38 MAPK signalling pathway, IL-8 release and airway epithelial cell apoptosis; the latter effect can be markedly potentiated by NTHi. Furthermore, budesonide can be very effective in preventing, through inhibition of p38 MAPK phosphorylation, both structural and proinflammatory changes elicited in bronchial epithelium by TNF-alpha and NTHi.

  5. KRAS mutation-positive bronchial surface epithelium (BSE)-type lung adenocarcinoma with strong expression of TTF-1: a case providing a further insight as for the role of TTF-1 in the oncogenesis.

    Science.gov (United States)

    Takanashi, Yusuke; Tajima, Shogo; Hayakawa, Takamitsu; Neyatani, Hiroshi; Funai, Kazuhito

    2015-01-01

    Bronchial surface epithelium (BSE)-type lung adenocarcinoma is a subtype of non-terminal respiratory unit (TRU)-type lung adenocarcinoma originating in the bronchial surface epithelium. However, there are few known cases of BSE-type adenocarcinoma with marked expression of thyroid transcription factor-1 (TTF-1). This paper describes a very rare case of KRAS mutation-positive BSE-type adenocarcinoma that exhibited strong expression of TTF-1 that was putatively involved in oncogenesis. An 84-year-old woman, a never smoker, was referred to our hospital because of an abnormal chest radiograph. Chest computed tomography (CT) showed a solid mass lesion, 15 mm × 10 mm, with a relatively smooth margin in the left upper lobe. The patient underwent partial resection of the left upper lobe for strongly suspected lung cancer with a clinical stage of cT1aN0M0. Histopathological findings showed continuous migration of papillary, hyperplastic, atypical columnar tumor cells originating from normal bronchial surface epithelium, leading to a diagnosis of BSE-type adenocarcinoma. TTF-1 was strongly expressed in almost 100% of the tumor cells, which tested positive for the KRAS mutation. TTF-1 has recently attracted attention as an oncogene, and it is purportedly involved in the carcinogenesis and survival of lung adenocarcinoma cells. There is typically an inverse correlation between the respective expressions of KRAS and TTF-1, but in the present study, they appeared simultaneously and were both putatively involved as oncogenic driver alterations. This case is important in that it sheds some light on the largely unknown pathogenic mechanism of BSE-type adenocarcinoma.

  6. XB130 translocation to microfilamentous structures mediates NNK-induced migration of human bronchial epithelial cells.

    Science.gov (United States)

    Wu, Qifei; Nadesalingam, Jeya; Moodley, Serisha; Bai, Xiaohui; Liu, Mingyao

    2015-07-20

    Cigarette smoking contributes to the pathogenesis of chronic obstructive pulmonary disease and lung cancer. Nicotine-derived nitrosamine ketone (NNK) is the most potent carcinogen among cigarette smoking components, and is known to enhance migration of cancer cells. However, the effect of NNK on normal human bronchial epithelial cells is not well studied. XB130 is a member of actin filament associated protein family and is involved in cell morphology changes, cytoskeletal rearrangement and outgrowth formation, as well as cell migration. We hypothesized that XB130 mediates NNK-induced migration of normal human bronchial epithelial cells. Our results showed that, after NNK stimulation, XB130 was translocated to the cell periphery and enriched in cell motility-associated structures, such as lamellipodia, in normal human bronchial epithelial BEAS2B cells. Moreover, overexpression of XB130 significantly enhanced NNK-induced migration, which requires both the N- and C-termini of XB130. Overexpression of XB130 enhanced NNK-induced protein tyrosine phosphorylation and promoted matrix metalloproteinase-14 translocation to cell motility-associated cellular structures after NNK stimulation. XB130-mediated NNK-induced cell migration may contribute to airway epithelial repair; however, it may also be involved in cigarette smoking-related chronic obstructive pulmonary disease and lung cancer.

  7. Rhinovirus-induced calcium flux triggers NLRP3 and NLRC5 activation in bronchial cells.

    Science.gov (United States)

    Triantafilou, Kathy; Kar, Satwik; van Kuppeveld, Frank J M; Triantafilou, Martha

    2013-12-01

    Human rhinoviruses have been linked with underlying lung disorders, such as asthma and chronic obstructive pulmonary disease, in children and adults. However, the mechanism of virus-induced airway inflammation is poorly understood. In this study, using virus deletion mutants and silencing for nucleotide-binding oligomerization domain-like receptors (NLRs), we show that the rhinovirus ion channel protein 2B triggers NLRP3 and NLRC5 inflammasome activation and IL-1β secretion in bronchial cells. 2B protein targets the endoplasmic reticulum and Golgi and induces Ca(2+) reduction in these organelles, thereby disturbing the intracellular calcium homeostasis. NLRP3 and NLRC5 act in a cooperative manner during the inflammasome assembly by sensing intracellular Ca(2+) fluxes and trigger IL-1β secretion. These results reveal for the first time that human rhinovirus infection in primary bronchial cells triggers inflammasome activation.

  8. deltaNp63 has a role in maintaining epithelial integrity in airway epithelium.

    Science.gov (United States)

    Arason, Ari Jon; Jonsdottir, Hulda R; Halldorsson, Skarphedinn; Benediktsdottir, Berglind Eva; Bergthorsson, Jon Thor; Ingthorsson, Saevar; Baldursson, Olafur; Sinha, Satrajit; Gudjonsson, Thorarinn; Magnusson, Magnus K

    2014-01-01

    The upper airways are lined with a pseudostratified bronchial epithelium that forms a barrier against unwanted substances in breathing air. The transcription factor p63, which is important for stratification of skin epithelium, has been shown to be expressed in basal cells of the lungs and its ΔN isoform is recognized as a key player in squamous cell lung cancer. However, the role of p63 in formation and maintenance of bronchial epithelia is largely unknown. The objective of the current study was to determine the expression pattern of the ΔN and TA isoforms of p63 and the role of p63 in the development and maintenance of pseudostratified lung epithelium in situ and in culture. We used a human bronchial epithelial cell line with basal cell characteristics (VA10) to model bronchial epithelium in an air-liquid interface culture (ALI) and performed a lentiviral-based silencing of p63 to characterize the functional and phenotypic consequences of p63 loss. We demonstrate that ΔNp63 is the major isoform in the human lung and its expression was exclusively found in the basal cells lining the basement membrane of the bronchial epithelium. Knockdown of p63 affected proliferation and migration of VA10 cells and facilitated cellular senescence. Expression of p63 is critical for epithelial repair as demonstrated by wound healing assays. Importantly, generation of pseudostratified VA10 epithelium in the ALI setup depended on p63 expression and goblet cell differentiation, which can be induced by IL-13 stimulation, was abolished by the p63 knockdown. After knockdown of p63 in primary bronchial epithelial cells they did not proliferate and showed marked senescence. We conclude that these results strongly implicate p63 in the formation and maintenance of differentiated pseudostratified bronchial epithelium.

  9. Oxidant-induced corticosteroid unresponsiveness in human bronchial epithelial cells

    NARCIS (Netherlands)

    Heijink, Irene; van Oosterhout, Antoon; Kliphuis, Nathalie; Jonker, Marnix; Hoffmann, Roland; Telenga, Eef; Klooster, Karin; Slebos, Dirk-Jan; ten Hacken, Nick; Postma, Dirkje; van den Berge, Maarten

    2014-01-01

    Background We hypothesised that increased oxidative stress, as present in the airways of asthma and chronic obstructive pulmonary disease (COPD) patients, induces epithelial damage and reduces epithelial responsiveness to suppressive effects of corticosteroids on proinflammatory cytokine production

  10. Ozone-induced injury and oxidative stress in bronchiolar epithelium are associated with altered pulmonary mechanics.

    Science.gov (United States)

    Sunil, Vasanthi R; Vayas, Kinal N; Massa, Christopher B; Gow, Andrew J; Laskin, Jeffrey D; Laskin, Debra L

    2013-06-01

    In these studies, we analyzed the effects of ozone on bronchiolar epithelium. Exposure of rats to ozone (2 ppm, 3 h) resulted in rapid (within 3 h) and persistent (up to 72 h) histological changes in the bronchiolar epithelium, including hypercellularity, loss of cilia, and necrotizing bronchiolitis. Perivascular edema and vascular congestion were also evident, along with a decrease in Clara cell secretory protein in bronchoalveolar lavage, which was maximal 24 h post-exposure. Ozone also induced the appearance of 8-hydroxy-2'-deoxyguanosine, Ym1, and heme oxygenase-1 in the bronchiolar epithelium. This was associated with increased expression of cleaved caspase-9 and beclin-1, indicating initiation of apoptosis and autophagy. A rapid and persistent increase in galectin-3, a regulator of epithelial cell apoptosis, was also observed. Following ozone exposure (3-24 h), increased expression of cyclooxygenase-2, inducible nitric oxide synthase, and arginase-1 was noted in bronchiolar epithelium. Ozone-induced injury and oxidative stress in bronchiolar epithelium were linked to methacholine-induced alterations in pulmonary mechanics. Thus, significant increases in lung resistance and elastance, along with decreases in lung compliance and end tidal volume, were observed at higher doses of methacholine. This indicates that ozone causes an increase in effective stiffness of the lung as a consequence of changes in the conducting airways. Collectively, these studies demonstrate that bronchiolar epithelium is highly susceptible to injury and oxidative stress induced by acute exposure to ozone; moreover, this is accompanied by altered lung functioning.

  11. MUC1 contributes to BPDE-induced human bronchial epithelial cell transformation through facilitating EGFR activation.

    Directory of Open Access Journals (Sweden)

    Xiuling Xu

    Full Text Available Although it is well known that epidermal growth factor receptor (EGFR is involved in lung cancer progression, whether EGFR contributes to lung epithelial cell transformation is less clear. Mucin 1 (MUC1 in human and Muc1 in animals, a glycoprotein component of airway mucus, is overexpressed in lung tumors; however, its role and underlying mechanisms in early stage lung carcinogenesis is still elusive. This study provides strong evidence demonstrating that EGFR and MUC1 are involved in bronchial epithelial cell transformation. Knockdown of MUC1 expression significantly reduced transformation of immortalized human bronchial epithelial cells induced by benzo[a]pyrene diol epoxide (BPDE, the active form of the cigarette smoke (CS carcinogen benzo(apyrene (BaPs. BPDE exposure robustly activated a pathway consisting of EGFR, Akt and ERK, and blocking this pathway significantly increased BPDE-induced cell death and inhibited cell transformation. Suppression of MUC1 expression resulted in EGFR destabilization and inhibition of the BPDE-induced activation of Akt and ERK and increase of cytotoxicity. These results strongly suggest an important role for EGFR in BPDE-induced transformation, and substantiate that MUC1 is involved in lung cancer development, at least partly through mediating carcinogen-induced activation of the EGFR-mediated cell survival pathway that facilitates cell transformation.

  12. Inhibitory effect of hydrogen sulfide on ozone-induced airway inflammation, oxidative stress, and bronchial hyperresponsiveness.

    Science.gov (United States)

    Zhang, Pengyu; Li, Feng; Wiegman, Coen H; Zhang, Min; Hong, Yan; Gong, Jicheng; Chang, Yan; Zhang, Junfeng Jim; Adcock, Ian; Chung, Kian Fan; Zhou, Xin

    2015-01-01

    Exposure to ozone has been associated with airway inflammation, oxidative stress, and bronchial hyperresponsiveness. The goal of this study was to examine whether these adverse effects of ozone could be prevented or reversed by hydrogen sulfide (H2S) as a reducing agent. The H2S donor sodium (NaHS) (2 mg/kg) or vehicle (PBS) was intraperitoneally injected into mice 1 hour before and after 3-hour ozone (2.5 ppm) or air exposure, and the mice were studied 24 hours later. Preventive and therapeutic treatment with NaHS reduced the ozone-induced increases in the total cells, including neutrophils and macrophages; this treatment also reduced levels of cytokines, including TNF-α, chemokine (C-X-C motif) ligand 1, IL-6, and IL-1β levels in bronchial alveolar lavage fluid; inhibited bronchial hyperresponsiveness; and attenuated ozone-induced increases in total malondialdehyde in bronchoalveolar lavage fluid and decreases in the ratio of reduced glutathione/oxidized glutathione in the lung. Ozone exposure led to decreases in the H2S production rate and in mRNA and protein levels of cystathionine-β-synthetase and cystathionine-γ-lyase in the lung. These effects were prevented and reversed by NaHS treatment. Furthermore, NaHS prevented and reversed the phosphorylation of p38 mitogen-activated protein kinase and heat shock protein 27. H2S may have preventive and therapeutic value in the treatment of airway diseases that have an oxidative stress basis.

  13. Molecular alterations in tumorigenic human bronchial and breast epithelial cells induced by high let radiation

    Science.gov (United States)

    Hei, T. K.; Zhao, Y. L.; Roy, D.; Piao, C. Q.; Calaf, G.; Hall, E. J.

    Carcinogenesis is a multi-stage process with sequence of genetic events governing the phenotypic expression of a series of transformation steps leading to the development of metastatic cancer. In the present study, immortalized human bronchial (BEP2D) and breast (MCF-10F) cells were irradiated with graded doses of either 150 keV/μm alpha particles or 1 GeV/nucleon 56Fe ions. Transformed cells developed through a series of successive steps before becoming tumorigenic in nude mice. Cell fusion studies indicated that radiation-induced tumorigenic phenotype in BEP2D cells could be completely suppressed by fusion with non-tumorigenic BEP2D cells. The differential expressions of known genes between tumorigenic bronchial and breast cells induced by alpha particles and their respective control cultures were compared using cDNA expression array. Among the 11 genes identified to be differentially expressed in BEP2D cells, three ( DCC, DNA-PK and p21 CIPI) were shown to be consistently down-regulated by 2 to 4 fold in all the 5 tumor cell lines examined. In contrast, their expressions in the fusion cell lines were comparable to control BEP2D cells. Similarly, expression levels of a series of genes were found to be altered in a step-wise manner among tumorigenic MCF-10F cells. The results are highly suggestive that functional alterations of these genes may be causally related to the carcinogenic process.

  14. Druse-Induced Morphology Evolution in Retinal Pigment Epithelium

    CERN Document Server

    Mazzitello, K I; Chrenek, M A; Family, F; Grossniklaus, H E; Nickerson, J M; Jiang, Y

    2016-01-01

    The retinal pigment epithelium (RPE) is a key site of pathogenesis for many retina diseases. The formation of drusen in the retina is characteristic of retinal degeneration. We investigate morphological changes in the RPE in the presence of soft drusen using an integrated experimental and modeling approach. We collect RPE flat mount images from donated human eyes and develop 1) statistical tools to quantify the images and 2) a cell-based model to simulate the morphology evolution. We compare three different mechanisms of RPE repair evolution, cell apoptosis, cell fusion, and expansion, and Simulations of our RPE morphogenesis model quantitatively reproduce deformations of human RPE morphology due to drusen, suggesting that a purse-string mechanism is sufficient to explain how RPE heals cell loss caused by drusen-damage. We found that drusen beneath tissue promote cell death in a number that far exceeds the cell numbers covering the drusen. Tissue deformations are studied using area distributions, Voronoi doma...

  15. Fetal-juvenile origins of point mutations in the adult human tracheal-bronchial epithelium: Absence of detectable effects of age, gender or smoking status

    Energy Technology Data Exchange (ETDEWEB)

    Sudo, Hiroko [Massachusetts Institute of Technology, Department of Biological Engineering, 21 Ames St., 16-743 Cambridge, MA 02139 (United States); Toray Industries, Inc., New Frontiers Research Laboratories 10-1, Tebiro 6-chome, Kamakura, Kanagawa 248-8555 (Japan); Li-Sucholeiki, Xiao-Cheng [Massachusetts Institute of Technology, Department of Biological Engineering, 21 Ames St., 16-743 Cambridge, MA 02139 (United States); Agencourt Bioscience Corp., 500 Cummings Center, Suite 2450, Beverly, MA 01915 (United States); Marcelino, Luisa A. [Massachusetts Institute of Technology, Department of Biological Engineering, 21 Ames St., 16-743 Cambridge, MA 02139 (United States); Biomedical Engineering Department, Northwestern University, 633 Clark Street, Evanston, IL 60208 (United States); Gruhl, Amanda N. [Massachusetts Institute of Technology, Department of Biological Engineering, 21 Ames St., 16-743 Cambridge, MA 02139 (United States); Herrero-Jimenez, Pablo [Massachusetts Institute of Technology, Department of Biological Engineering, 21 Ames St., 16-743 Cambridge, MA 02139 (United States); SLC Ontario, 690 Dorval Drive, Suite 200, Oakville, Ontario L6K 3W7 Canada (Canada); Zarbl, Helmut [UMDNJ-Robert Wood Johnson Medical School, Environmental and Occupational Health Sciences Institute, 170 Freylinghuysen Road, Room 426, Piscataway, NJ 08854 (United States); Willey, James C. [Medical College of Ohio, 3120 Glendale Avenue, Room 12, Toledo, OH 43614 (United States); Furth, Emma E. [University of Pennsylvania Medical Center, Department of Pathology, 3400 Spruce Street, 6 Founders Building, Philadelphia, PA 19104 (United States); Morgenthaler, Stephan [Institute of Applied Mathematics, Swiss Federal Institute of Technology (EPFL), SB/IMA, 1015 Lausanne (Switzerland)] (and others)

    2008-11-10

    Allele-specific mismatch amplification mutation assays (MAMA) of anatomically distinct sectors of the upper bronchial tracts of nine nonsmokers revealed many numerically dispersed clusters of the point mutations C742T, G746T, G747T of the TP53 gene, G35T of the KRAS gene and G508A of the HPRT1 gene. Assays of these five mutations in six smokers have yielded quantitatively similar results. One hundred and eighty four micro-anatomical sectors of 0.5-6 x 10{sup 6} tracheal-bronchial epithelial cells represented en toto the equivalent of approximately 1.7 human smokers' bronchial trees to the fifth bifurcation. Statistically significant mutant copy numbers above the 95% upper confidence limits of historical background controls were found in 198 of 425 sector assays. No significant differences (P = 0.1) for negative sector fractions, mutant fractions, distributions of mutant cluster size or anatomical positions were observed for smoking status, gender or age (38-76 year). Based on the modal cluster size of mitochondrial point mutants, the size of the adult bronchial epithelial maintenance turnover unit was estimated to be about 32 cells. When data from all 15 lungs were combined the log 2 of nuclear mutant cluster size plotted against log 2 of the number of clusters of a given cluster size displayed a slope of {approx}1.1 over a range of cluster sizes from {approx}2{sup 6} to 2{sup 15} mutant copies. A parsimonious interpretation of these nuclear and previously reported data for lung epithelial mitochondrial point mutant clusters is that they arose from mutations in stem cells at a high but constant rate per stem cell doubling during at least ten stem cell doublings of the later fetal-juvenile period. The upper and lower decile range of summed point mutant fractions among lungs was about 7.5-fold, suggesting an important source of stratification in the population with regard to risk of tumor initiation.

  16. Bronchial provocation testing does not detect exercise-induced laryngeal obstruction

    DEFF Research Database (Denmark)

    Walsted, Emil Schwarz; Hull, James H; Sverrild, Asger;

    2016-01-01

    and possible asthma referred over 6 months. All subjects received comprehensive assessment including a detailed clinical evaluation; pulmonary function testing, indirect and direct bronchial provocation testing, and CLE testing. Results Out of 37 subjects, moderate or severe EILO was diagnosed in 8 subjects......Introduction Exercise-induced laryngeal obstruction (EILO) is a key differential diagnosis for asthma in the presence of exertional respiratory symptoms. Continuous laryngoscopy during exercise (CLE), the current gold standard diagnostic test for EILO, has practical limitations. We aimed...... to establish if inspiratory flow data obtained during standard bronchoprovocation testing, to establish the presence of extra-thoracic hyper-responsiveness, may prove diagnostic for EILO and thus preclude requirement for CLE testing. Methods We consecutively evaluated 37 adult subjects with exertional dyspnoea...

  17. Neutrophil and asbestos fiber-induced cytotoxicity in cultured human mesothelial and bronchial epithelial cells.

    Science.gov (United States)

    Kinnula, V L; Raivio, K O; Linnainmaa, K; Ekman, A; Klockars, M

    1995-03-01

    This study investigates reactive oxygen species generation and oxidant-related cytotoxicity induced by amosite asbestos fibers and polymorphonuclear leucocytes (PMNs) in human mesothelial cells and human bronchial epithelial cells in vitro. Transformed human pleural mesothelial cells (MET 5A) and bronchial epithelial cells (BEAS 2B) were treated with amosite (2 micrograms/cm2) for 48 h. After 24 h of incubation, the cells were exposed for 1 h to nonactivated or amosite (50 micrograms) activated PMNs, washed, and incubated for another 23 h. Reactive oxygen species generation by the PMNs and the target cells was measured by chemiluminescence. Cell injury was assessed by cellular adenine nucleotide depletion, extracellular release of nucleotides, and lactate dehydrogenase (LDH). Amosite-activated (but also to a lesser degree nonactivated) PMNs released substantial amounts of reactive oxygen metabolites, whereas the chemiluminescence of amosite-exposed mesothelial cells and epithelial cells did not differ from the background. Amosite treatment (48 h) of the target cells did not change intracellular adenine nucleotides (ATP, ADP, AMP) or nucleotide catabolite products (xanthine, hypoxanthine, and uric acid). When the target cells were exposed to nonactivated PMNs, significant adenine nucleotide depletion and nucleotide catabolite accumulation was observed in mesothelial cells only. In separate experiments, when the target cells were exposed to amosite-activated PMNs, the target cell injury was further potentiated compared with the amosite treatment alone or exposure to nonactivated PMNs. In conclusion, this study suggests the importance of inflammatory cell-derived free radicals in the development of amosite-induced mesothelial cell injury.

  18. BRONCHIAL LAVAGE AND BRONCHOALVEOLAR LAVAGE IN ALLERGEN-INDUCED SINGLE EARLY AND DUAL ASTHMATIC RESPONDERS

    NARCIS (Netherlands)

    AALBERS, R; KAUFFMAN, HF; VRUGT, B; SMITH, M; KOETER, GH; TIMENS, W; DEMONCHY, JGR

    1993-01-01

    The phenotypic cellular profile of bronchial lavage (BL) and bronchoalveolar lavage (BAL) was studied in 7 single early (SR) and 10 dual asthmatic responders (DR). Lavage was performed, after previously having determined bronchial hyperresponsiveness to histamine and the response to house dust mite

  19. Sesame Oil Attenuates Ovalbumin-Induced Pulmonary Edema and Bronchial Neutrophilic Inflammation in Mice

    Directory of Open Access Journals (Sweden)

    Dur-Zong Hsu

    2013-01-01

    Full Text Available Background. Allergic asthma is one of the most common chronic inflammatory diseases of airways. Severe asthma may lead to hospitalization and death. Sesame oil is a natural product with anti-inflammatory property. However, the effect of sesame oil on allergic asthma has never been studied. Objective. We investigate the effect of sesame oil on pulmonary inflammation in allergic asthma model. Methods. Allergic airway inflammation was induced by sensitizing with two doses of 10 mg ovalbumin (OVA and then challenged with 1% OVA nebulizer exposure (1 h/day for 3 days. Sesame oil (0.25, 0.5, or 1 mL/kg/day was given orally 30 min before each challenge. Samples were collected 24 h after the last challenge. Results. Data showed that sesame oil inhibited pulmonary edema and decreased interleukin (IL-1β and IL-6 levels in bronchoalveolar lavage fluid in OVA-treated mice. Sesame oil also decreased pulmonary nitrite level, inducible nitric oxide synthase expression, and neutrophil infiltration induced by OVA. Further, sesame oil decreased serum IgE level in OVA-treated mice. Conclusion. Sesame oil may attenuate pulmonary edema and bronchial neutrophilic inflammation by inhibiting systemic IgE level in allergic asthma.

  20. Montelukast prevents microparticle-induced inflammatory and functional alterations in human bronchial smooth muscle cells.

    Science.gov (United States)

    Fogli, Stefano; Stefanelli, Fabio; Neri, Tommaso; Bardelli, Claudio; Amoruso, Angela; Brunelleschi, Sandra; Celi, Alessandro; Breschi, Maria Cristina

    2013-10-01

    Microparticles (MPs) are membrane fragments that may play a role in the pathogenesis of chronic respiratory diseases. We aimed to investigate whether human monocytes/macrophage-derived MPs could induce a pro-inflammatory phenotype in human bronchial smooth muscle cells (BSMC) and the effect of montelukast in this setting. Experimental methods included isolation of human monocytes/macrophages and generation of monocyte-derived MPs, RT-PCR analysis of gene expression, immunoenzymatic determination of pro-inflammatory factor release, bioluminescent assay of intracellular cAMP levels and electromobility shift assay analysis of NF-κB nuclear translocation. Stimulation of human BSMC with monocyte-derived MPs induced a pro-inflammatory switch in human BSMC by inducing gene expression (COX-2 and IL-8), protein release in the supernatant (PGE2 and IL-8), and heterologous β2-adrenoceptor desensitization. The latter effect was most likely related to autocrine PGE2 since pre-treatment with COX inhibitors restored the ability of salbutamol to induce cAMP synthesis in desensitized cells. Challenge with MPs induced nuclear translocation of NF-κB and selective NF-κB inhibition decreased MP-induced cytokine release in the supernatant. Montelukast treatment prevented IL-8 release and heterologous β2-adrenoceptor desensitization in human BSMC exposed to monocyte-derived MPs by blocking NF-κB nuclear translocation. These findings provide evidence on the role of human monocyte-derived MPs in the airway smooth muscle phenotype switch as a novel potential mechanism in the progression of chronic respiratory diseases and on the protective effects by montelukast in this setting.

  1. Interleukin-13-induced mucous metaplasia increases susceptibility of human airway epithelium to rhinovirus infection.

    Science.gov (United States)

    Lachowicz-Scroggins, Marrah E; Boushey, Homer A; Finkbeiner, Walter E; Widdicombe, Jonathan H

    2010-12-01

    Infection of airway epithelium by rhinovirus is the most common cause of asthma exacerbations. Even in mild asthma, airway epithelium exhibits mucous metaplasia, which increases with increasing severity of the disease. We previously showed that squamous cultures of human airway epithelium manifest rhinoviral infection at levels many times higher than in well-differentiated cultures of a mucociliary phenotype. Here we tested the hypothesis that mucous metaplasia is also associated with increased levels of rhinoviral infection. Mucous metaplasia was induced with IL-13, which doubled the numbers of goblet cells. In both control (mucociliary) and IL-13- treated (mucous metaplastic) cultures, goblet cells were preferentially infected by rhinovirus. IL-13 doubled the numbers of infected cells by increasing the numbers of infected goblet cells. Furthermore, IL-13 increased both the maturity of goblet cells and the probability that a goblet cell would be infected. The infection of cells other than goblet cells was unaltered by IL-13. Treatment with IL-13 did not alter the levels of rhinovirus receptor ICAM-1, nor did the proliferative effects of IL-13 enhance infection, because rhinovirus did not colocalize with dividing cells. However, the induction of mucous metaplasia caused changes in the apical membrane structure, notably a marked decrease in overall ciliation, and an increase in the overall flatness of the apical surface. We conclude that mucous metaplasia in asthma increases the susceptibility of airway epithelium to infection by rhinovirus because of changes in the overall architecture of the apical surface.

  2. PKC activation induces inflammatory response and cell death in human bronchial epithelial cells.

    Directory of Open Access Journals (Sweden)

    Hyunhee Kim

    Full Text Available A variety of airborne pathogens can induce inflammatory responses in airway epithelial cells, which is a crucial component of host defence. However, excessive inflammatory responses and chronic inflammation also contribute to different diseases of the respiratory system. We hypothesized that the activation of protein kinase C (PKC is one of the essential mechanisms of inflammatory response in airway epithelial cells. In the present study, we stimulated human bronchial lung epithelial (BEAS-2B cells with the phorbol ester Phorbol 12, 13-dibutyrate (PDBu, and examined gene expression profile using microarrays. Microarray analysis suggests that PKC activation induced dramatic changes in gene expression related to multiple cellular functions. The top two interaction networks generated from these changes were centered on NFκB and TNF-α, which are two commonly known pathways for cell death and inflammation. Subsequent tests confirmed the decrease in cell viability and an increase in the production of various cytokines. Interestingly, each of the increased cytokines was differentially regulated at mRNA and/or protein levels by different sub-classes of PKC isozymes. We conclude that pathological cell death and cytokine production in airway epithelial cells in various situations may be mediated through PKC related signaling pathways. These findings suggest that PKCs can be new targets for treatment of lung diseases.

  3. Retinoic acid from retinal pigment epithelium induces T regulatory cells.

    Science.gov (United States)

    Kawazoe, Yuko; Sugita, Sunao; Keino, Hiroshi; Yamada, Yukiko; Imai, Ayano; Horie, Shintaro; Mochizuki, Manabu

    2012-01-01

    Primary cultured retinal pigment epithelial (RPE) cells can convert T cells into T regulatory cells (Tregs) through inhibitory factor(s) including transforming growth factor β (TGFβ) in vitro. Retinoic acid (RA) enhances induction of CD4(+) Tregs in the presence of TGFβ. We investigated whether RA produced by RPE cells can promote generation of Tregs. We found that in vitro, RA-treated T cells expressed high levels of Foxp3 in the presence of recombinant TGFβ. In GeneChip analysis, cultured RPE cells constitutively expressed RA-associated molecules such as RA-binding proteins, enzymes, and receptors. RPE from normal mice, but not vitamin A-deficient mice, contained significant levels of TGFβ. RPE-induced Tregs from vitamin A-deficient mice failed to suppress activation of target T cells. Only a few Foxp3(+) T cells were found in intraocular cells from vitamin A-deficient experimental autoimmune uveitis (EAU) mice, whereas expression was higher in cells from normal EAU mice. RA receptor antagonist-pretreated or RA-binding protein-siRNA-transfected RPE cells failed to convert CD4(+) T cells into Tregs. Our data support the hypothesis that RPE cells produce RA, thereby enabling bystander T cells to be converted into Tregs through TGFβ promotion, which can then participate in the establishment of immune tolerance in the eye.

  4. Lithium Attenuates TGF-β1-Induced Fibroblasts to Myofibroblasts Transition in Bronchial Fibroblasts Derived from Asthmatic Patients

    Directory of Open Access Journals (Sweden)

    Marta Michalik

    2012-01-01

    Full Text Available Bronchial asthma is a chronic disorder accompanied by phenotypic transitions of bronchial epithelial cells, smooth muscle cells, and fibroblasts. Human bronchial fibroblasts (HBFs derived from patients with diagnosed asthma display predestination towards TGF-β-induced phenotypic switches. Since the interference between TGF-β and GSK-3β signaling contributes to pathophysiology of chronic lung diseases, we investigated the effect of lithium, a nonspecific GSK-3β inhibitor, on TGF-β1-induced fibroblast to myofibroblast transition (FMT in HBF and found that the inhibition of GSK-3β attenuates TGF-β1-induced FMT in HBF populations derived from asthmatic but not healthy donors. Cytoplasmically sequestrated β-catenin, abundant in TGF-β1/LiCl-stimulated asthmatic HBFs, most likely interacts with and inhibits the nuclear accumulation and signal transduction of Smad proteins. These data indicate that the specific cellular context determines FMT-related responses of HBFs to factors interfering with the TGF-β signaling pathway. They may also provide a mechanistic explanation for epidemiological data revealing coincidental remission of asthmatic syndromes and their recurrence upon the discontinuation of lithium therapy in certain psychiatric diseases.

  5. ALLERGEN-INDUCED CHANGES IN ADENOSINE 5'-MONOPHOSPHATE BRONCHIAL RESPONSIVENESS - EFFECT OF NEDOCROMIL SODIUM

    NARCIS (Netherlands)

    AALBERS, R; KAUFMAN, HF; GROEN, H; KOETER, GH; DEMONCHY, JGR

    1992-01-01

    Bronchial hyperresponsiveness to adenosine 5'-monophosphate (AMP) was studied after allergen challenge in allergic asthmatic patients. Measurements were made with and without nedocromil sodium pretreatment. Nedocromil sodium inhibited both the early and late asthmatic reactions (P <.01). After aller

  6. Diesel exhaust particle-induced cell death of cultured normal human bronchial epithelial cells.

    Science.gov (United States)

    Matsuo, Mitsuyoshi; Shimada, Toshio; Uenishi, Rie; Sasaki, Naoko; Sagai, Masaru

    2003-04-01

    We investigated the effect of diesel exhaust particles (DEPs) on normal human bronchial epithelial (NHBE) cells. Inclusion of DEPs in culture media was lethal to NHBE cells. NHBE cells are more susceptible to DEPs than other normal human lung cells, normal human pulmonary artery endothelial cells and normal human embryonic lung fibroblasts. DEP-induced cell death was mainly due to necrosis. Using the fluorescence probes diacetoxymethyl 6-carboxy-3',6'-diacetoxy-2',7'-dichloro-3',6'-dideoxydihydrofluorescinate and 4,5-diaminofluorescein diacetate, it was observed that hydrogen peroxide and nitrogen monoxide, respectively, were generated within DEP-exposed NHBE cells. DEP cytotoxicity increased or decreased with an increase or decrease in the cellular level of reduced glutathione (GSH) by treatment with L-buthionine-(R,S)-sulfoximine or ethyl reduced glutathionate, respectively. In addition, DEPs themselves decreased the cellular level of GSH in a dose-dependent manner. Upon exposure of NHBE cells to high concentrations of DEPs, their cellular GSH was depleted almost throughout. Further, the following agents decreased DEP cytotoxicity: 1) antioxidants 2,2,5,7,8-pentamethylchroman-6-ol, ebselen, and N,N'-bis(salicylidene)ethylenediaminomanganese(II) dihydrate (EUK-8); 2) iron ion-chelating agents disodium bathophenanthrolinedisulfonate and desferrioxamine mesylate; 3) nitrogen monoxide synthase inhibitors N(G)-nitro-L-arginine methyl ester hydrochloride and N(G)-methyl-L-arginine acetate salt; and 4) an endocytosis inhibitor quinacrine. On the basis of these observations, the mechanism of DEP cytotoxicity toward NHBE cells is discussed.

  7. Bronchial hyperresponsiveness and analysis of induced sputum cells in Crohn's disease

    Directory of Open Access Journals (Sweden)

    R.M. Bartholo

    2005-02-01

    Full Text Available With the aim of investigating the presence of latent inflammatory process in the lungs of patients with Crohn's disease, 15 patients with Crohn's disease were evaluated by spirometry, the methacholine challenge test, induced sputum, and skin tests for inhaled antigens. Serum IgE, erythrocyte sedimentation rate and hematocrit were also determined. The patients were compared with 20 healthy controls by the Mann-Whitney and Fisher exact tests. Their respiratory physical examination was normal. None had a personal or family history of clinical atopy. None had a previous history of pulmonary disease, smoking or toxic bronchopulmonary exposure. None had sinusitis, migraine, diabetes mellitus, or cardiac failure. Four (26.6% of the patients with Crohn's disease had a positive methacholine challenge test whereas none of the 20 controls had a positive methacholine test (P = 0.026, Fisher exact test. Patients with Crohn's disease had a higher level of lymphocytes in induced sputum than controls (mean 14.59%, range 3.2-50 vs 5.46%, 0-26.92%, respectively; P = 0.011, Mann-Whitney test. Patients with Crohn's disease and a positive methacholine challenge test had an even higher percentage of lymphocytes in induced sputum compared with patients with Crohn's disease and a negative methacholine test (mean 24.88%, range 12.87-50 vs 10.48%, 3.2-21.69%; P = 0.047, Mann-Whitney test. The simultaneous findings of bronchopulmonary lymphocytosis and bronchial hyperresponsiveness in patients with Crohn's disease were not reported up to now. These results suggest that patients with Crohn's disease present a subclinical inflammatory process despite the absence of pulmonary symptoms.

  8. Puerarin protects human bronchial epithelial cells from apoptosis induced by gunpowder smog

    Directory of Open Access Journals (Sweden)

    Yun-xia CHEN

    2016-03-01

    Full Text Available Objective  To investigate protective effects of puerarin on the human bronchial epithelial (BEAS-2B cell line against apoptosis caused by gunpowder smog and its mechanisms. Methods  BEAS-2B cells cultured in vitro were randomly divided into control group, smog group (the group treated with 4g gunpowder smog for 10min, and smog + puerarin group [puerarin group, the cells were pre-incubated with various concentrations of puerarin (12.5, 25.0, 50.0, 100.0µg/ml and then exposed to smoke]. Puerarin was added into the cells after innoculation for 12h and then the cells were sequentially cultured for 24h and followed by exposure to smoke for 10min. After being cultured again for 2h, the smoked cells were examined for cell viability using Cell Counting Kit-8(CCK-8, cell apoptosis was observed using Hoechst33258 nucleus staining, and positive rates of Annexin V-PI staining cells and caspase-3 were determined with flow cytometer. Resu lts  Compared with control, treatment of BEAS-2B cells with 4g gunpowder smog induced a characteristic apoptotic cell death (P<0.01. Pretreatment with various concentrations of puerarin antagonized the action of gunpowder smog in different degrees. The 25µg/ml was determined as the optimal effective concentration of puerarin. Compared with smog group, the apoptosis rate of BEAS-2B cells and positive rates of Annexin V-PI staining cells and caspase-3 were decreased significantly in smog + puerarin group (P<0.05, P<0.01. Conclusion  Gunpowder smog can induce apoptosis of BEAS-2B cells in vitro, while pretreatment with puerarin could protect BEAS-2B cells against apoptosis induced by gunpowder smog. DOI: 10.11855/j.issn.0577-7402.2016.01.16

  9. HAIR CELL-LIKE CELL GENERATION INDUCED BY NATURE CULTURE OF ADULT RAT AUDITORY EPITHELIUM

    Institute of Scientific and Technical Information of China (English)

    Liu Hui; Zhu Hongliang; Li Shengli; Yao Xiaobao; Wang Xiaoxia

    2006-01-01

    Objective To establish adult rat auditory epithelial cell culture and try to find precursor cells of auditory hair cells in vitro. Methods With refinement of culture media and techniques, cochlear sensory epithelial cells of adult rat were cultured. Immunocytochemistry and Bromodeoxyuridine (BrdU)labeling were used to detect properties and mitotic status of cultured cells. Results The cultured auditory epithelial cells showed a large, flat epithelial morphotype and expressed F-actin and cytokeratin, a subset of cells generated from auditory epithelium were labeled by calretinin, a specific marker of early hair cell. Conclusion Adult rat auditory epithelium can be induced to generate hair cell-like cells by nature culture, this phenomenon suggests that progenitor cells may exist in rat cochlea and they may give birth to new hair cells. Whether these progenitor cells are tissue specific stem cells is still need more study.

  10. Pulmonary proteases in the cystic fibrosis lung induce interleukin 8 expression from bronchial epithelial cells via a heme/meprin/epidermal growth factor receptor/Toll-like receptor pathway.

    LENUS (Irish Health Repository)

    Cosgrove, Sonya

    2012-02-01

    A high intrapulmonary protease burden is characteristic of cystic fibrosis (CF), and the resulting dysregulation of the protease\\/anti-protease balance has serious implications for inflammation in the CF lung. Because of this inflammation, micro-bleeds can occur releasing hemoglobin into the lung. The aim of this study was to investigate the effect of the protease-rich environment of the CF lung on human hemoglobin and to assess the proinflammatory effect of heme on CF bronchial epithelium. Here, we show that the Pseudomonas proteases (Pseudomonas elastase and alkaline protease) and the neutrophil proteases (neutrophil elastase (NE) and proteinase-3) are capable of almost complete degradation of hemoglobin in vitro but that NE is the predominant protease that cleaves hemoglobin in vivo in CF bronchoalveolar lavage fluid. One of the effects of this is the release of heme, and in this study we show that heme stimulates IL-8 and IL-10 protein production from DeltaF508 CFBE41o(-) bronchial epithelial cells. In addition, heme-induced IL-8 expression utilizes a novel pathway involving meprin, EGF receptor, and MyD88. Meprin levels are elevated in CF cell lines and bronchial brushings, thus adding to the proinflammatory milieu. Interestingly, alpha(1)-antitrypsin, in addition to its ability to neutralize NE and protease-3, can also bind heme and neutralize heme-induced IL-8 from CFBE41o(-) cells. This study illustrates the proinflammatory effects of micro-bleeds in the CF lung, the process by which this occurs, and a potential therapeutic intervention.

  11. Pulmonary Proteases in the Cystic Fibrosis Lung Induce Interleukin 8 Expression from Bronchial Epithelial Cells via a Heme/Meprin/Epidermal Growth Factor Receptor/Toll-like Receptor Pathway.

    LENUS (Irish Health Repository)

    Cosgrove, Sonya

    2011-03-04

    A high intrapulmonary protease burden is characteristic of cystic fibrosis (CF), and the resulting dysregulation of the protease\\/anti-protease balance has serious implications for inflammation in the CF lung. Because of this inflammation, micro-bleeds can occur releasing hemoglobin into the lung. The aim of this study was to investigate the effect of the protease-rich environment of the CF lung on human hemoglobin and to assess the proinflammatory effect of heme on CF bronchial epithelium. Here, we show that the Pseudomonas proteases (Pseudomonas elastase and alkaline protease) and the neutrophil proteases (neutrophil elastase (NE) and proteinase-3) are capable of almost complete degradation of hemoglobin in vitro but that NE is the predominant protease that cleaves hemoglobin in vivo in CF bronchoalveolar lavage fluid. One of the effects of this is the release of heme, and in this study we show that heme stimulates IL-8 and IL-10 protein production from ΔF508 CFBE41o(-) bronchial epithelial cells. In addition, heme-induced IL-8 expression utilizes a novel pathway involving meprin, EGF receptor, and MyD88. Meprin levels are elevated in CF cell lines and bronchial brushings, thus adding to the proinflammatory milieu. Interestingly, α(1)-antitrypsin, in addition to its ability to neutralize NE and protease-3, can also bind heme and neutralize heme-induced IL-8 from CFBE41o(-) cells. This study illustrates the proinflammatory effects of micro-bleeds in the CF lung, the process by which this occurs, and a potential therapeutic intervention.

  12. TGFβ signaling in lung epithelium regulates bleomycin-induced alveolar injury and fibroblast recruitment.

    Science.gov (United States)

    Degryse, Amber L; Tanjore, Harikrishna; Xu, Xiaochuan C; Polosukhin, Vasiliy V; Jones, Brittany R; Boomershine, Chad S; Ortiz, Camila; Sherrill, Taylor P; McMahon, Frank B; Gleaves, Linda A; Blackwell, Timothy S; Lawson, William E

    2011-06-01

    The response of alveolar epithelial cells (AECs) to lung injury plays a central role in the pathogenesis of pulmonary fibrosis, but the mechanisms by which AECs regulate fibrotic processes are not well defined. We aimed to elucidate how transforming growth factor-β (TGFβ) signaling in lung epithelium impacts lung fibrosis in the intratracheal bleomycin model. Mice with selective deficiency of TGFβ receptor 2 (TGFβR2) in lung epithelium were generated and crossed to cell fate reporter mice that express β-galactosidase (β-gal) in cells of lung epithelial lineage. Mice were given intratracheal bleomycin (0.08 U), and the following parameters were assessed: AEC death by terminal deoxynucleotidyl transferase dUTP-mediated nick-end labeling assay, inflammation by total and differential cell counts from bronchoalveolar lavage, fibrosis by scoring of trichrome-stained lung sections, and total lung collagen content. Mice with lung epithelial deficiency of TGFβR2 had improved AEC survival, despite greater lung inflammation, after bleomycin administration. At 3 wk after bleomycin administration, mice with epithelial TGFβR2 deficiency showed a significantly attenuated fibrotic response in the lungs, as determined by semiquantitatve scoring and total collagen content. The reduction in lung fibrosis in these mice was associated with a marked decrease in the lung fibroblast population, both total lung fibroblasts and epithelial-to-mesenchymal transition-derived (S100A4(+)/β-gal(+)) fibroblasts. Attenuation of TGFβ signaling in lung epithelium provides protection from bleomycin-induced fibrosis, indicating a critical role for the epithelium in transducing the profibrotic effects of this cytokine.

  13. The inhibitory mechanism of Cordyceps sinensis on cigarette smoke extract-induced senescence in human bronchial epithelial cells

    Directory of Open Access Journals (Sweden)

    Liu AL

    2016-07-01

    Full Text Available Ailing Liu,1,2,* Jinxiang Wu,1,* Aijun Li,2 Wenxiang Bi,3 Tian Liu,1 Liuzhao Cao,1 Yahui Liu,1 Liang Dong1 1Department of Pulmonary Diseases, Qilu Hospital, Shandong University, Jinan, Shandong, People’s Republic of China; 2Department of Pulmonary Diseases, Weihai Municipal Hospital, Weihai, Shandong, People’s Republic of China; 3Institute of Biochemistry and Molecular Biology, School of Medicine, Shandong University, Jinan, Shandong, People’s Republic of China *These authors contributed equally to this work Objectives: Cellular senescence is a state of irreversible growth arrest induced either by telomere shortening (replicative senescence or stress. The bronchial epithelial cell is often injured by inhaled toxic substances, such as cigarette smoke. In the present study, we investigated whether exposure to cigarette smoke extract (CSE induces senescence of bronchial epithelial cells; and Cordyceps sinensis mechanism of inhibition of CSE-induced cellular senescence.Methods: Human bronchial epithelial cells (16HBE cells cultured in vitro were treated with CSE and/or C. sinensis. p16, p21, and senescence-associated-galactosidase activity were used to detect cellular senescence with immunofluorescence, quantitative polymerase chain reaction, and Western blotting. Reactive oxygen species (ROS, PI3K/AKT/mTOR and their phosphorylated proteins were examined to testify the activation of signaling pathway by ROS fluorescent staining and Western blotting. Then, inhibitors of ROS and PI3K were used to further confirm the function of this pathway.Results: Cellular senescence was upregulated by CSE treatment, and C. sinensis can decrease CSE-induced cellular senescence. Activation of ROS/PI3K/AKT/mTOR signaling pathway was enhanced by CSE treatment, and decreased when C. sinensis was added. Blocking ROS/PI3K/AKT/mTOR signaling pathway can attenuate CSE-induced cellular senescence.Conclusion: CSE can induce cellular senescence in human bronchial

  14. NiO nanoparticles induce apoptosis through repressing SIRT1 in human bronchial epithelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Duan, Wei-Xia; He, Min-Di; Mao, Lin [Department of Occupational Health, Third Military Medical University, Chongqing 400038 (China); Qian, Feng-Hua [Department of Hematology, Southwest Hospital, Third Military Medical University, Chongqing 400038 (China); Li, Yu-Ming [Institute of Hepatobiliary Surgery, XinQiao Hospital, Third Military Medical University, Chongqing 400038 (China); Pi, Hui-Feng; Liu, Chuan; Chen, Chun-Hai; Lu, Yong-Hui; Cao, Zheng-Wang; Zhang, Lei; Yu, Zheng-Ping [Department of Occupational Health, Third Military Medical University, Chongqing 400038 (China); Zhou, Zhou, E-mail: lunazhou00@163.com [Department of Occupational Health, Third Military Medical University, Chongqing 400038 (China)

    2015-07-15

    With application of nano-sized nickel-containing particles (Nano-Ni) expanding, the health concerns about their adverse effects on the pulmonary system are increasing. However, the mechanisms for the pulmonary toxicity of these materials remain unclear. In the present study, we focused on the impacts of NiO nanoparticles (NiONPs) on sirtuin1 (SIRT1), a NAD-dependent deacetylase, and investigated whether SIRT1 was involved in NiONPs-induced apoptosis. Although the NiONPs tended to agglomerate in fluid medium, they still entered into the human bronchial epithelial cells (BEAS-2B) and released Ni{sup 2+} inside the cells. NiONPs at doses of 5, 10, and 20 μg/cm{sup 2} inhibited the cell viability. NiONPs' produced cytotoxicity was demonstrated through an apoptotic process, indicated by increased numbers of Annexin V positive cells and caspase-3 activation. The expression of SIRT1 was markedly down-regulated by the NiONPs, accompanied by the hyperacetylation of p53 (tumor protein 53) and overexpression of Bax (Bcl-2-associated X protein). However, overexpression of SIRT1 through resveratrol treatment or transfection clearly attenuated the NiONPs-induced apoptosis and activation of p53 and Bax. Our results suggest that the repression of SIRT1 may underlie the NiONPs-induced apoptosis via p53 hyperacetylation and subsequent Bax activation. Because SIRT1 participates in multiple biologic processes by deacetylation of dozens of substrates, this knowledge of the impact of NiONPs on SIRT1 may lead to an improved understanding of the toxic mechanisms of Nano-Ni and provide a molecular target to antagonize Nano-Ni toxicity. - Highlights: • NiONPs were taken up by BEAS-2B cells and released Ni{sup 2+}. • NiONPs produced cytotoxicity was demonstrated through an apoptotic process. • NiONPs repressed SIRT1 expression and activated p53 and Bax. • Overexpression of SIRT1 attenuated NiONPs-induced apoptosis via deacetylation p53.

  15. Autophagy is essential for ultrafine particle-induced inflammation and mucus hyperproduction in airway epithelium.

    Science.gov (United States)

    Chen, Zhi-Hua; Wu, Yin-Fang; Wang, Ping-Li; Wu, Yan-Ping; Li, Zhou-Yang; Zhao, Yun; Zhou, Jie-Sen; Zhu, Chen; Cao, Chao; Mao, Yuan-Yuan; Xu, Feng; Wang, Bei-Bei; Cormier, Stephania A; Ying, Song-Min; Li, Wen; Shen, Hua-Hao

    2016-01-01

    Environmental ultrafine particulate matter (PM) is capable of inducing airway injury, while the detailed molecular mechanisms remain largely unclear. Here, we demonstrate pivotal roles of autophagy in regulation of inflammation and mucus hyperproduction induced by PM containing environmentally persistent free radicals in human bronchial epithelial (HBE) cells and in mouse airways. PM was endocytosed by HBE cells and simultaneously triggered autophagosomes, which then engulfed the invading particles to form amphisomes and subsequent autolysosomes. Genetic blockage of autophagy markedly reduced PM-induced expression of inflammatory cytokines, e.g. IL8 and IL6, and MUC5AC in HBE cells. Mice with impaired autophagy due to knockdown of autophagy-related gene Becn1 or Lc3b displayed significantly reduced airway inflammation and mucus hyperproduction in response to PM exposure in vivo. Interference of the autophagic flux by lysosomal inhibition resulted in accumulated autophagosomes/amphisomes, and intriguingly, this process significantly aggravated the IL8 production through NFKB1, and markedly attenuated MUC5AC expression via activator protein 1. These data indicate that autophagy is required for PM-induced airway epithelial injury, and that inhibition of autophagy exerts therapeutic benefits for PM-induced airway inflammation and mucus hyperproduction, although they are differentially orchestrated by the autophagic flux.

  16. Oestrus synchronization treatment induces histomorphological changes on the uterine tube epithelium of the gilt.

    Science.gov (United States)

    Juárez-Mosqueda, M L; Anzaldúa Arce, S R; Palma Lara, I; García Dalmán, C; Cornejo Cortés, M A; Córdova Izquierdo, A; Villaseñor Gaona, H; Trujillo Ortega, M E

    2015-12-01

    The aim of this study was to determine the histomorphological changes that occurred in response to two treatments for oestrus synchronization in three different regions of the gilt's uterine tubes epithelium: the ampulla (AMP), ampulla-isthmic junction (AIJ) and isthmus (IST). Nine prepuberal gilts were divided into three groups (n = 3): (1) eCG 400 IU and hCG 200 IU (eCG/hCG), (2) progesterone agonist (P4) and (3) control group. The number of secretory cells (stained with periodic acid-Schiff reaction or PAS-positive cells) decreased in the AMP in the P4 treated group when compared to the control group, whereas, no difference was observed in the number of PAS-negative cells in the AMP of the three groups. A significant decrease in the number of PAS-positive cells was observed in the AIJ and IST of the P4 treated group when compared to the eCG/hCG and control groups. An increase in the number of PAS-negative cells was observed in the AIJ and IST in the P4 treated group. The epithelium height in the AMP and AIJ was increased in the eCG/hCG group when compared to the control and P4 groups. In this last group, we observed a reduced height compared with the other two groups for the AIJ. In the IST, there were no significant changes in the epithelium height of the control or the other two groups (eCG/hCG and P4). The epithelial cells of the P4 treated group had the least amount of cytoplasmic granules and the lowest intensity of PAS staining in the AMP, AIJ and IST. Animals treated with eCG/hCG showed an intermediate number of cytoplasmic granules and intensity in all regions evaluated. These data show that P4 treatment for synchronization induces a significant (P epithelium. Moreover, eCG/hCG treatment increased the height of the epithelium in the AMP and AIJ, while in this last region, the P4 treatment decreased the epithelium height. These results show that synchronization treatments with P4 and in a smaller proportion with eCG/hCG can modify the amount of PAS

  17. The function and significance of SELENBP1 downregulation in human bronchial epithelial carcinogenic process.

    Directory of Open Access Journals (Sweden)

    Gu-Qing Zeng

    Full Text Available BACKGROUND: Our quantitative proteomic study showed that selenium-binding protein 1 (SELENBP1 was progressively decreased in human bronchial epithelial carcinogenic process. However, there is little information on expression and function of SELENBP1 during human lung squamous cell cancer (LSCC carcinogenesis. METHODS: iTRAQ-tagging combined with 2D LC-MS/MS analysis was used to identify differentially expressed proteins in the human bronchial epithelial carcinogenic process. SELENBP1, member of selenoproteins family and progressively downregulated in this process, was selected to further study. Both Western blotting and immunohistochemistry were performed to detect SELENBP1 expression in independent sets of tissues of bronchial epithelial carcinogenesis, and ability of SELENBP1 for discriminating NBE (normal bronchial epithelium from preneoplastic lesions from invasive LSCC was evaluated. The effects of SELENBP1 downregulation on the susceptibility of benzo(apyrene (B[a]P-induced human bronchial epithelial cell transformation were determined. RESULTS: 102 differentially expressed proteins were identified by quantitative proteomics, and SELENBP1 was found and confirmed being progressively decreased in the human bronchial epithelial carcinogenic process. The sensitivity and specificity of SELENBP1 were 80% and 79% in discriminating NBE from preneoplastic lesions, 79% and 82% in discriminating NBE from invasive LSCC, and 77% and 71% in discriminating preneoplastic lesions from invasive LSCC, respectively. Furthermore, knockdown of SELENBP1 in immortalized human bronchial epithelial cell line 16HBE cells significantly increased the efficiency of B[a]P-induced cell transformation. CONCLUSIONS: The present data shows for the first time that decreased SELENBP1 is an early event in LSCC, increases B[a]P-induced human bronchial epithelial cell transformation, and might serve as a novel potential biomarker for early detection of LSCC.

  18. High Fructose Diet inducing diabetes rapidly impacts olfactory epithelium and behavior in mice

    Science.gov (United States)

    Rivière, Sébastien; Soubeyre, Vanessa; Jarriault, David; Molinas, Adrien; Léger-Charnay, Elise; Desmoulins, Lucie; Grebert, Denise; Meunier, Nicolas; Grosmaitre, Xavier

    2016-01-01

    Type 2 Diabetes (T2D), a major public health issue reaching worldwide epidemic, has been correlated with lower olfactory abilities in humans. As olfaction represents a major component of feeding behavior, its alteration may have drastic consequences on feeding behaviors that may in turn aggravates T2D. In order to decipher the impact of T2D on the olfactory epithelium, we fed mice with a high fructose diet (HFruD) inducing early diabetic state in 4 to 8 weeks. After only 4 weeks of this diet, mice exhibited a dramatic decrease in olfactory behavioral capacities. Consistently, this decline in olfactory behavior was correlated to decreased electrophysiological responses of olfactory neurons recorded as a population and individually. Our results demonstrate that, in rodents, olfaction is modified by HFruD-induced diabetes. Functional, anatomical and behavioral changes occurred in the olfactory system at a very early stage of the disease. PMID:27659313

  19. ADAM10 mediates the house dust mite-induced release of chemokine ligand CCL20 by airway epithelium

    NARCIS (Netherlands)

    Post, S.; Rozeveld, D.; Jonker, M. R.; Bischoff, R.; van Oosterhout, A. J.; Heijink, I. H.

    2015-01-01

    Background: House dust mite (HDM) acts on the airway epithelium to induce airway inflammation in asthma. We previously showed that the ability of HDM to induce allergic sensitization in mice is related to airway epithelial CCL20 secretion. Objective: As a disintegrin and metalloprotease (ADAM)s have

  20. Bronchial, alveolar, and vascular-induced anaphylaxis and irritant-induced cardiovascular and pulmonary responses.

    OpenAIRE

    Yeates, D B; Mussatto, D J; Hameister, W M; Daza, A.; Chandra, T; Wong, L B

    2001-01-01

    We examine the respiratory, bronchomotor, cardiac, and vascular responses to histamine and ragweed allergen delivered to the bronchi or alveoli compartments and the potential role of sensory nerves and reflexes mediating the histamine-induced responses. The masses of aerosols deposited in the bronchi and alveoli were quantitated using radioaerosol techniques. Activation of sensory nerves and/or histamine-induced mediator release were characterized by depositing nedocromil sodium aerosol prior...

  1. DNA strand breaks in human nasal respiratory epithelium are induced upon exposure to urban pollution

    Energy Technology Data Exchange (ETDEWEB)

    Calderon-Garciduenas, L.; Osnaya-Brizuela, N.; Ramirez-Martinez, L. [Instituto Nacional de Pediatria, Mexico City (Mexico)] [and others

    1996-02-01

    All organisms have the ability to respond and adapt to a myriad of environmental insults. The human respiratory epithelium, when exposed to oxidant gases in photochemical smog, is at risk of DNA damage and requires efficient cellular adaptative responses to resist the environmentally induced cell damage. Ozone and its reaction products induce in vitro and in vivo DNA single strand breaks (SSBs) in respiratory epithelial cells and alveolar macrophages. To determine if exposure to a polluted atmosphere with ozone as the main criteria pollutant of 19 children and 13 adult males who lived in a low-polluted Pacific port, 69 males and 16 children who were permanent residents of Southwest Metropolitan Mexico City (SWMMC), and 22 young males newly arrived to SWMMC and followed for 12 weeks. Respiratory symptoms, nasal cytology and histopathology, cell viabilities, and single-cell gel electrophoresis were investigated. Atmospheric pollutant data were obtained from a fixed-site monitoring station. SWMMC volunteers spent >7 hr/day outdoors and all had upper respiratory symptoms. A significant difference in the numbers of DNA-damaged nasal cells was observed between control and chronically exposed subjects, both in children (p<0.00001) and in adults (p>0.01). SSBs in newly arrived subjects quickly increased upon arrival to the city, from 39.8 {+-}8.34% in the first week to 67.29 {+-}2.35 by week 2. Thereafter, the number of cells with SSBs remained stable in spite of the continuous increase in cumulative ozone, suggesting a threshold for cumulative DNA nasal damage. Exposure to a polluted urban atmosphere induces SSBs in human nasal respiratory epithelium, and nasal SSBs could serve as a biomarker of ozone exposure. Further, because DNA strand breaks are a threat to cell viability and genome integrity and appear to be a critical lesion responsible for p53 induction, nasal SSBs should be evaluated in ozone-exposed individuals. 43 refs., 5 figs., 4 tabs.

  2. Light-Induced Phosphorylation of Crystallins in the Retinal Pigment Epithelium

    Science.gov (United States)

    Lee, Hyunju; Chung, Hyewon; Lee, Sung Haeng; Jahng, Wan Jin

    2017-01-01

    Protein phosphorylations have essential regulatory roles in visual signaling. Previously, we found that phosphorylation of several proteins in the retina and the retinal pigment epithelium (RPE) is involved in anti-apoptotic signaling under oxidative stress conditions, including light exposure. In this study, we used a phosphoprotein enrichment strategy to evaluate the light-induced phosphoproteome of primary bovine RPE cells. Phosphoprotein-enriched extracts from bovine RPE cells exposed to light or dark conditions for 1 hour were separated by 2D SDS-PAGE. Serine and tyrosine phosphorylation were visualized by 2D phospho western blotting and specific phosphorylation sites were analyzed by tandem mass spectrometry. Light induced a marked increase in tyrosine phosphorylation of beta crystallin A3 and A4. The most abundant light-induced up-regulated phosphoproteins were crystallins of 15–25-kDa, including beta crystallin S and zeta crystallin. Phosphorylation of beta crystallin suggests an anti-apoptotic chaperone function in the RPE. Other chaperones, cytoskeletal proteins, and proteins involved in energy balance were expressed at higher levels in the dark. A detailed analysis of RPE phosphoproteins provides a molecular basis for understanding light-induced signal transduction and anti-apoptosis mechanisms. Our data indicates that phosphorylation of crystallins likely represents an important mechanism for RPE shielding from physiological and pathophysiological light-induced oxidative injury. PMID:21094180

  3. Free radical generation induces epithelial-to-mesenchymal transition in lung epithelium via a TGF-β1-dependent mechanism.

    Science.gov (United States)

    Gorowiec, Marta R; Borthwick, Lee A; Parker, Sean M; Kirby, John A; Saretzki, Gabriele C; Fisher, Andrew J

    2012-03-15

    Fibrotic remodelling of lung parenchymal and airway compartments is the major contributor to life-threatening organ dysfunction in chronic lung diseases such as idiopathic pulmonary fibrosis (IPF) and Chronic Obstructive Pulmonary Disease (COPD). Since transforming growth factor-β1 (TGF-β1) is believed to play a key role in disease pathogenesis and markers of oxidative stress are also commonly detected in bronchoalveolar lavage (BAL) from such patients we sought to investigate whether both factors might be interrelated. Here we investigated the hypothesis that oxidative stress to the lung epithelium promotes fibrotic repair by driving epithelial-to-mesenchymal transition (EMT) via the augmentation of TGF-β1. We show that in response to 400μM hydrogen peroxide (H(2)O(2)) A549 cells, used a model for alveolar epithelium, and human primary bronchial epithelial cells (PBECs) undergo EMT displaying morphology changes, decreased expression of epithelial markers (E-cadherin and ZO-1), increased expression of mesenchymal markers (vimentin and α-smooth muscle actin) as well as increased secretion of extracelluar matrix components. The same oxidative stress also promotes expression of TGF-β1. Inhibition of TGF-β1 signalling as well as treatment with antioxidants such as phenyl tert-butylnitrone (PBN) and superoxide dismutase 3 (SOD3) prevent the oxidative stress driven EMT-like changes described above. Interventions also inhibited EMT-like changes. This study identifies a link between oxidative stress, TGF-β1 and EMT in lung epithelium and highlights the potential for antioxidant therapies to limit EMT and its potential contribution to chronic lung disease.

  4. WNT/β-catenin pathway modulates the TNF-α-induced inflammatory response in bronchial epithelial cells.

    Science.gov (United States)

    Jang, Jaewoong; Jung, Yoonju; Chae, Seyeon; Chung, Sang-In; Kim, Seok-Min; Yoon, Yoosik

    2017-03-04

    In this study, TNF-α was found to activate the WNT/β-catenin pathway in BEAS-2B human bronchial epithelial cells. Levels of phospho-LRP6, Dvl-2, and phospho-GSK-3β were elevated, while that of Axin was reduced by TNF-α treatment. Nuclear translocation of β-catenin and the reporter activity of a β-catenin-responsive promoter were increased by TNF-α treatment. Under the same experimental conditions, TNF-α activated the NF-κB signaling, which includes the phosphorylation and degradation of IκB and nuclear translocation and target DNA binding of NF-κB, and it was found that an inhibitor of NF-κB activation, JSH-23, inhibited TNF-α-induced Wnt signaling as well as NF-κB signaling. It was also found that recombinant Wnt proteins induced NF-κB nuclear translocations and its target DNA binding, suggesting that Wnt signaling and NF-κB signaling were inter-connected. TNF-α-induced modulations of IκB and NF-κB as well as pro-inflammatory cytokine expression were significantly suppressed by the transfection of β-catenin siRNA compared to that of control siRNA. Transfection of a β-catenin expression plasmid augmented the TNF-α-induced modulations of IκB and NF-κB as well as pro-inflammatory cytokine expression. These results clearly demonstrated that the WNT/β-catenin pathway modulates the inflammatory response induced by TNF-α, suggesting that this pathway may be a useful target for the effective treatment of bronchial inflammation.

  5. Involvement of HIF-2α-mediated inflammation in arsenite-induced transformation of human bronchial epithelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Xu, Yuan; Zhao, Yue; Xu, Wenchao; Luo, Fei; Wang, Bairu; Li, Yuan; Pang, Ying; Liu, Qizhan, E-mail: drqzliu@hotmail.com

    2013-10-15

    Arsenic is a well established human carcinogen that causes diseases of the lung. Some studies have suggested a link between inflammation and lung cancer; however, it is unknown if arsenite-induced inflammation causally contributes to arsenite-caused malignant transformation of cells. In this study, we investigated the molecular mechanisms underlying inflammation during neoplastic transformation induced in human bronchial epithelial (HBE) cells by chronic exposure to arsenite. The results showed that, on acute or chronic exposure to arsenite, HBE cells over-expressed the pro-inflammatory cytokines, interleukin-6 (IL-6), interleukin-8 (IL-8), and interleukin-1β (IL-1β). The data also indicated that HIF-2α was involved in arsenite-induced inflammation. Moreover, IL-6 and IL-8 were essential for the malignant progression of arsenite-transformed HBE cells. Thus, these experiments show that HIF-2α mediates arsenite-induced inflammation and that such inflammation is involved in arsenite-induced malignant transformation of HBE cells. The results provide a link between the inflammatory response and the acquisition of a malignant transformed phenotype by cells chronically exposed to arsenite and thus establish a previously unknown mechanism for arsenite-induced carcinogenesis. - Highlights: • Arsenite induces inflammation. • Arsenite-induced the increases of IL-6 and IL-8 via HIF-2α. • Inflammation is involved in arsenite-induced carcinogenesis.

  6. Smoking-induced CXCL14 expression in the human airway epithelium links chronic obstructive pulmonary disease to lung cancer.

    Science.gov (United States)

    Shaykhiev, Renat; Sackrowitz, Rachel; Fukui, Tomoya; Zuo, Wu-Lin; Chao, Ion Wa; Strulovici-Barel, Yael; Downey, Robert J; Crystal, Ronald G

    2013-09-01

    CXCL14, a recently described epithelial cytokine, plays putative multiple roles in inflammation and carcinogenesis. In the context that chronic obstructive pulmonary disease (COPD) and lung cancer are both smoking-related disorders associated with airway epithelial disorder and inflammation, we hypothesized that the airway epithelium responds to cigarette smoking with altered CXCL14 gene expression, contributing to the disease-relevant phenotype. Using genome-wide microarrays with subsequent immunohistochemical analysis, the data demonstrate that the expression of CXCL14 is up-regulated in the airway epithelium of healthy smokers and further increased in COPD smokers, especially within hyperplastic/metaplastic lesions, in association with multiple genes relevant to epithelial structural integrity and cancer. In vitro experiments revealed that the expression of CXCL14 is induced in the differentiated airway epithelium by cigarette smoke extract, and that epidermal growth factor mediates CXCL14 up-regulation in the airway epithelium through its effects on the basal stem/progenitor cell population. Analyses of two independent lung cancer cohorts revealed a dramatic up-regulation of CXCL14 expression in adenocarcinoma and squamous-cell carcinoma. High expression of the COPD-associated CXCL14-correlating cluster of genes was linked in lung adenocarcinoma with poor survival. These data suggest that the smoking-induced expression of CXCL14 in the airway epithelium represents a novel potential molecular link between smoking-associated airway epithelial injury, COPD, and lung cancer.

  7. Interleukin-13–Induced Mucous Metaplasia Increases Susceptibility of Human Airway Epithelium to Rhinovirus Infection

    OpenAIRE

    2010-01-01

    Infection of airway epithelium by rhinovirus is the most common cause of asthma exacerbations. Even in mild asthma, airway epithelium exhibits mucous metaplasia, which increases with increasing severity of the disease. We previously showed that squamous cultures of human airway epithelium manifest rhinoviral infection at levels many times higher than in well-differentiated cultures of a mucociliary phenotype. Here we tested the hypothesis that mucous metaplasia is also associated with increas...

  8. Serosal zinc attenuate serotonin and vasoactive intestinal peptide induced secretion in piglet small intestinal epithelium in vitro

    DEFF Research Database (Denmark)

    Carlson, Dorthe; Sehested, Jakob; Feng, Z

    2008-01-01

    This study addressed the mechanisms by which dietary zinc affects diarrhoea and aimed to study possible interactions between zinc status and the presence of zinc in vitro on secretagogue-induced secretion from piglet intestinal epithelium in Ussing chambers....

  9. Cannabinoid-induced autophagy regulates suppressor of cytokine signaling-3 in intestinal epithelium.

    Science.gov (United States)

    Koay, Luan C; Rigby, Rachael J; Wright, Karen L

    2014-07-15

    Autophagy is a catabolic process involved in homeostatic and regulated cellular protein recycling and degradation via the lysosomal degradation pathway. Emerging data associate impaired autophagy, increased activity in the endocannabinoid system, and upregulation of suppressor of cytokine signaling-3 (SOCS3) protein expression during intestinal inflammation. We have investigated whether these three processes are linked. By assessing the impact of the phytocannabinoid cannabidiol (CBD), the synthetic cannabinoid arachidonyl-2'-chloroethylamide (ACEA), and the endocannabinoid N-arachidonoylethanolamine (AEA) on autophagosome formation, we explored whether these actions were responsible for cyclic SOCS3 protein levels. Our findings show that all three cannabinoids induce autophagy in a dose-dependent manner in fully differentiated Caco-2 cells, a model of mature intestinal epithelium. ACEA and AEA induced canonical autophagy, which was cannabinoid type 1 receptor-mediated. In contrast, CBD was able to bypass the cannabinoid type 1 receptor and the canonical pathway to induce autophagy, albeit to a lesser extent. Functionally, all three cannabinoids reduced SOCS3 protein expression, which was reversed by blocking early and late autophagy. In conclusion, the regulatory protein SOCS3 is regulated by autophagy, and cannabinoids play a role in this process, which could be important when therapeutic applications for the cannabinoids in inflammatory conditions are considered.

  10. Abnormal Expression of Eukaryotic Translation Factors in Malignant Transformed Human Bronchial Epithelial Cells Induced by Crystalline Nickel Sulfide

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Objective To study the oncogenic potential of mouse translation initiation factor 3 (TIF3) and elongation factor-1δ (TEF-1δ) in malignant transformed human bronchial epithelial cells induced by crystalline nickel sulfide (NiS). Methods Abnormal expressions of human TIF3 and TEF-1δ genes in two kinds of NiS-transformed cells and NiS-tumorigenic cell lines were investigated and analyzed by the reverse transcript polymerase chain reaction (RT-PCR) and fluorescent quantitative polymerase chain reaction (FQ-PCR), respectively. Results RT-PCR analysis primarily showed that both human TIF3 and TEF-1δ mRNA expressions in two kinds of NiS-transformed cells and NiS-tumorigenic cell lines were increased as compared with controls. FQ-PCR assay showed that the levels of TIF3 expressions in the transformed cells and tumorigenic cells were 3 and 4 times higher respectively, and the elevated expressions of TEF-1δ cDNA copies were 2.7- to 3.5-fold in transformed cells and 4.1- to 5.2-fold in tumorigenic cells when compared with non-transformed cells, indicating that the over-expressions of human TIF3 and TEF-1δ genes were related to malignant degree of the cells induced by nickel. Conclusions These findings demonstrate that there are markedly abnormal expressions of TIF3 and TEF-1δ genes during malignant transformation of human bronchial epithelial cell lines induced by crystalline NiS. They seem to be the molecular mechanisms potentially responsible for human carcinogensis due to nickel.

  11. Choline acetyltransferase and organic cation transporters are responsible for synthesis and propionate-induced release of acetylcholine in colon epithelium.

    Science.gov (United States)

    Bader, Sandra; Klein, Jochen; Diener, Martin

    2014-06-15

    Acetylcholine is not only a neurotransmitter, but is found in a variety of non-neuronal cells. For example, the enzyme choline acetyltransferase (ChAT), catalyzing acetylcholine synthesis, is expressed by the colonic epithelium of different species. These cells release acetylcholine across the basolateral membrane after luminal exposure to propionate, a short-chain fatty acid. The functional consequence is the induction of chloride secretion, measurable as increase in short-circuit current (Isc) in Ussing chamber experiments. It is unclear how acetylcholine is produced and released by colonic epithelium. Therefore, the aim of the present study was the identification (on mRNA and protein level) and functional characterization (in Ussing chamber experiments combined with HPLC detection of acetylcholine) of transporters/enzymes in the cholinergic system of rat colonic epithelium. Immunohistochemical staining as well as RT-PCR revealed the expression of high-affinity choline transporter, ChAT, carnitine acetyltransferase (CarAT), vesicular acetylcholine transporter (VAChT), and organic cation transporters (OCT 1, 2, 3) in colonic epithelium. In contrast to blockade of ChAT with bromoacetylcholine, inhibition of CarAT with mildronate did not inhibit the propionate-induced increase in Isc, suggesting a predominant synthesis of epithelial acetylcholine by ChAT. Although being expressed, blockade of VAChT with vesamicol was ineffective, whereas inhibition of OCTs with omeprazole and corticosterone inhibited propionate-induced Isc and the release of acetylcholine into the basolateral compartment. In summary, OCTs seem to be involved in regulated acetylcholine release by colonic epithelium, which is assumed to be involved in chemosensing of luminal short-chain fatty acids by the intestinal epithelium.

  12. Pigment Epithelium-Derived Factor Alleviates Tamoxifen-Induced Endometrial Hyperplasia.

    Science.gov (United States)

    Goldberg, Keren; Bar-Joseph, Hadas; Grossman, Hadas; Hasky, Noa; Uri-Belapolsky, Shiri; Stemmer, Salomon M; Chuderland, Dana; Shalgi, Ruth; Ben-Aharon, Irit

    2015-12-01

    Tamoxifen is a cornerstone component of adjuvant endocrine therapy for patients with hormone-receptor-positive breast cancer. Its significant adverse effects include uterine hyperplasia, polyps, and increased risk of endometrial cancer. However, the underlying molecular mechanism remains unclear. Excessive angiogenesis, a hallmark of tumorigenesis, is a result of disrupted balance between pro- and anti-angiogenic factors. VEGF is a pro-angiogenic factor shown to be elevated by tamoxifen in the uterus. Pigment epithelium-derived factor (PEDF) is a potent anti-angiogenic factor that suppresses strong pro-angiogenic factors, such as VEGF. Our aim was to investigate whether angiogenic balance plays a role in tamoxifen-induced uterine pathologies, elucidate the molecular impairment in that network, and explore potential intervention to offset the proposed imbalance elicited by tamoxifen. Using in vivo mouse models, we demonstrated that tamoxifen induced a dose-dependent shift in endogenous uterine angiogenic balance favoring VEGF over PEDF. Treatment with recombinant PEDF (rPEDF) abrogated tamoxifen-induced uterine hyperplasia and VEGF elevation, resulting in reduction of blood vessels density. Exploring the molecular mechanism revealed that tamoxifen promoted survival and malignant transformation pathways, whereas rPEDF treatment prevents these changes. Activation of survival pathways was decreased, demonstrated by reduction in AKT phosphorylation concomitant with elevation in JNK phosphorylation. Estrogen receptor-α and c-Myc oncoprotein levels were reduced. Our findings provide novel insight into the molecular mechanisms tamoxifen induces in the uterus, which may become the precursor events of subsequent endometrial hyperplasia and cancer. We demonstrate that rPEDF may serve as a useful intervention to alleviate the risk of tamoxifen-induced endometrial pathologies.

  13. Phosphorylation of p65 Is Required for Zinc Oxide Nanoparticle–Induced Interleukin 8 Expression in Human Bronchial Epithelial Cells

    OpenAIRE

    Wu, Weidong; Samet, James M.; Peden, David B.; Bromberg, Philip A.

    2010-01-01

    Background Exposure to zinc oxide (ZnO) in environmental and occupational settings causes acute pulmonary responses through the induction of proinflammatory mediators such as interleukin-8 (IL-8). Objective We investigated the effect of ZnO nanoparticles on IL-8 expression and the underlying mechanisms in human bronchial epithelial cells. Methods We determined IL-8 mRNA and protein expression in primary human bronchial epithelial cells and the BEAS-2B human bronchial epithelial cell line usin...

  14. Wood dusts induce the production of reactive oxygen species and caspase-3 activity in human bronchial epithelial cells.

    Science.gov (United States)

    Pylkkänen, Lea; Stockmann-Juvala, Helene; Alenius, Harri; Husgafvel-Pursiainen, Kirsti; Savolainen, Kai

    2009-08-21

    Wood dusts are associated with several respiratory symptoms, e.g. impaired lung function and asthma, in exposed workers. However, despite the evidence from epidemiological studies, the underlying mechanisms are not well understood. In the present study, we investigated different wood dusts for their capacity to induce cytotoxicity and production of radical oxygen species (ROS) as well as activation of the apoptotic caspase-3 enzyme in human bronchial epithelial cells (BEAS-2B). Dusts from three different tree species widely used in wood industry were studied; birch and oak represented hardwood species, and pine a common softwood species. All the experiments were carried out in three different concentrations (10, 50, and 500 microg/ml) and the analysis was performed after 0.5, 2, 6, and 24h exposure. All wood dusts studied were cytotoxic to human bronchial epithelial cells in a dose-dependent manner after 2 and 6h treatment. Exposure to pine, birch, or oak dust had a significant stimulating effect on the production of ROS. Also an induction in caspase-3 protease activity, one of the central components of the apoptotic cascade, was seen in BEAS-2B cells after 2 and 6h exposure to each of the wood dusts studied. In summary, we demonstrate that dusts from pine, birch and oak are cytotoxic, able to increase the production of ROS and the apoptotic response in human broncho-epithelial cells in vitro. Thus, our current data suggest oxidative stress by ROS as an important mechanism likely to function in wood dust related pulmonary toxicity although details of the cellular targets and cell-particle interactions remain to be solved. It is though tempting to speculate that redox-regulated transcription factors such as NFkappaB or AP-1 may play a role in this wood dust-evoked process leading to apparently induced apoptosis of target cells.

  15. Transgenic overexpression of cdx1b induces metaplastic changes of gene expression in zebrafish esophageal squamous epithelium.

    Science.gov (United States)

    Hu, Bo; Chen, Hao; Liu, Xiuping; Zhang, Chengjin; Cole, Gregory J; Lee, Ju-Ahng; Chen, Xiaoxin

    2013-06-01

    Cdx2 has been suggested to play an important role in Barrett's esophagus or intestinal metaplasia (IM) in the esophagus. To investigate whether transgenic overexpression of cdx1b, the functional equivalent of mammalian Cdx2 in zebrafish, may lead to IM of zebrafish esophageal squamous epithelium, a transgenic zebrafish system was developed by expressing cdx1b gene under the control of zebrafish keratin 5 promoter (krt5p). Gene expression in the esophageal squamous epithelium of wild-type and transgenic zebrafish was analyzed by Affymetrix microarray and confirmed by in situ hybridization. Morphology, mucin expression, cell proliferation, and apoptosis were analyzed by hematoxylin & eosin (HE) staining, Periodic acid Schiff (PAS) Alcian blue staining, proliferating cell nuclear antigen (PCNA) immunohistochemical staining, and TUNEL assay as well. cdx1b was found to be overexpressed in the nuclei of esophageal squamous epithelial cells of the transgenic zebrafish. Ectopic expression of cdx1b disturbed the development of this epithelium in larval zebrafish and induced metaplastic changes in gene expression in the esophageal squamous epithelial cells of adult zebrafish, that is, up-regulation of intestinal differentiation markers and down-regulation of squamous differentiation markers. However, cdx1b failed to induce histological IM, or to modulate cell proliferation and apoptosis in the squamous epithelium of adult transgenic zebrafish.

  16. Proinflammatory cytokine responses induced by influenza A (H5N1 viruses in primary human alveolar and bronchial epithelial cells

    Directory of Open Access Journals (Sweden)

    Poon LLM

    2005-11-01

    Full Text Available Abstract Background Fatal human respiratory disease associated with influenza A subtype H5N1 has been documented in Hong Kong, and more recently in Vietnam, Thailand and Cambodia. We previously demonstrated that patients with H5N1 disease had unusually high serum levels of IP-10 (interferon-gamma-inducible protein-10. Furthermore, when compared with human influenza virus subtype H1N1, the H5N1 viruses in 1997 (A/Hong Kong/483/97 (H5N1/97 were more potent inducers of pro-inflammatory cytokines (e.g. tumor necrosis factor-a and chemokines (e.g. IP-10 from primary human macrophages in vitro, which suggests that cytokines dysregulation may play a role in pathogenesis of H5N1 disease. Since respiratory epithelial cells are the primary target cell for replication of influenza viruses, it is pertinent to investigate the cytokine induction profile of H5N1 viruses in these cells. Methods We used quantitative RT-PCR and ELISA to compare the profile of cytokine and chemokine gene expression induced by H5N1 viruses A/HK/483/97 (H5N1/97, A/Vietnam/1194/04 and A/Vietnam/3046/04 (both H5N1/04 with that of human H1N1 virus in human primary alveolar and bronchial epithelial cells in vitro. Results We demonstrated that in comparison to human H1N1 viruses, H5N1/97 and H5N1/04 viruses were more potent inducers of IP-10, interferon beta, RANTES (regulated on activation, normal T cell expressed and secreted and interleukin 6 (IL-6 in primary human alveolar and bronchial epithelial cells in vitro. Recent H5N1 viruses from Vietnam (H5N1/04 appeared to be even more potent at inducing IP-10 than H5N1/97 virus. Conclusion The H5N1/97 and H5N1/04 subtype influenza A viruses are more potent inducers of proinflammatory cytokines and chemokines in primary human respiratory epithelial cells than subtype H1N1 virus. We suggest that this hyper-induction of cytokines may be relevant to the pathogenesis of human H5N1 disease.

  17. Hypotonicity induced K+ and anion conductive pathways activation in eel intestinal epithelium

    DEFF Research Database (Denmark)

    Lionetto, M G; Giordano, M E; De Nuccio, F

    2005-01-01

    , the activation of 'emergency' systems of rapid cell volume regulation is fundamental in their physiology. The aim of the present work was to study the physiological response to hypotonic stress in a salt-transporting epithelium, the intestine of the euryhaline teleost Anguilla anguilla. Eel intestinal epithelium......(te)) and the short circuit current (I(sc)). This electrophysiological response correlated with a regulatory volume decrease (RVD) response, recorded by morphometrical measurement of the epithelium height. Changes in the transepithelial resistance were also observed following the hypotonicity exposure...

  18. Bronchial stents

    Directory of Open Access Journals (Sweden)

    Ibrahim Emad

    2006-01-01

    Full Text Available Bronchial stents are mostly used as a Palliative relief of symptoms often caused by airway obstruction, It is also used for sealing of stump fistulas after pneumonectomy and dehiscence after bronchoplastic operations. Advances in airway prosthetics have provided a variety of silicone stents, expandable metal stents, and pneumatic dilators, enabling the correction of increasingly complex anatomical problems. Several series have been published describing the application and results of these techniques. This manuscript reviews the historical development of stents, types, indication, outcome, and complications. Alternative therapies for tracheobronchial stenting were also reviewed

  19. TGFβ signaling in lung epithelium regulates bleomycin-induced alveolar injury and fibroblast recruitment

    OpenAIRE

    Degryse, Amber L.; Tanjore, Harikrishna; Xu, Xiaochuan C.; Polosukhin, Vasiliy V.; Jones, Brittany R.; Chad S Boomershine; Ortiz, Camila; Sherrill, Taylor P.; McMahon, Frank B.; Gleaves, Linda A.; Blackwell, Timothy S.; Lawson, William E.

    2011-01-01

    The response of alveolar epithelial cells (AECs) to lung injury plays a central role in the pathogenesis of pulmonary fibrosis, but the mechanisms by which AECs regulate fibrotic processes are not well defined. We aimed to elucidate how transforming growth factor-β (TGFβ) signaling in lung epithelium impacts lung fibrosis in the intratracheal bleomycin model. Mice with selective deficiency of TGFβ receptor 2 (TGFβR2) in lung epithelium were generated and crossed to cell fate reporter mice tha...

  20. Overexpression of Sprouty 2 in Mouse Lung Epithelium Inhibits Urethane-Induced Tumorigenesis

    OpenAIRE

    Minowada, George; Miller, York E.

    2008-01-01

    Members of the Sprouty family encode novel proteins that are thought to function primarily as intracellular antagonists of the Ras-signaling pathway. Increased Ras signaling is a critical characteristic of human lung adenocarcinoma, the most common type of non–small cell lung cancer. Sprouty 2 is expressed in the lung epithelium, the tissue layer from which lung cancers arise. We hypothesized that overexpression of Sprouty 2 in the distal lung epithelium would inhibit lung tumorigenesis. To t...

  1. Immunotoxic effects of low level ozone exposure suggestive of an inducers in bronchial hyperresponiveness

    Institute of Scientific and Technical Information of China (English)

    SongH; LiDM

    2002-01-01

    For the city pollution of motor vehicle emissions,public air oxidizer exposure level has increasing tendence.As a representative of osidizer,ozone exposure is universal expecially at low levels in big city.Summarizing previous experimental study,which focuses on the exposure concentration at 0.125 ppm,the changes in inflammatory cytokines in animal airway suggest that low levels ozone expose activate cytokines resembling the bronchial hyperresponsiveness of atopy.Similarly the epidemiological study on adverse effects of ambient ozone exposure showed that the lower maxinal mid-expiratory flow of achoold children in exposed area where the concentration of ozone exceeded background levels only in the periphery of petroleum chemical enterprise were observed compared with those in control ares(P<0.05).This phenomenon of airway resistance increases as well as laboratory observation suggests that low level oxidizer exposure is one of the main risk factors of result in the increasing incidence of asthma in cities.

  2. Airway Epithelium Stimulates Smooth Muscle Proliferation

    OpenAIRE

    Malavia, Nikita K.; Raub, Christopher B.; Mahon, Sari B.; Brenner, Matthew; Reynold A Panettieri; George, Steven C.

    2009-01-01

    Communication between the airway epithelium and stroma is evident during embryogenesis, and both epithelial shedding and increased smooth muscle proliferation are features of airway remodeling. Hence, we hypothesized that after injury the airway epithelium could modulate airway smooth muscle proliferation. Fully differentiated primary normal human bronchial epithelial (NHBE) cells at an air–liquid interface were co-cultured with serum-deprived normal primary human airway smooth muscle cells (...

  3. YThe BigH3 Tumor Suppressor Gene in Radiation-Induced Malignant Transformation of Human Bronchial Epithelial Cells

    Science.gov (United States)

    Zhao, Y.; Shao, G.; Piao, C.; Hei, T.

    Carcinogenesis is a multi-stage process with sequences of genetic events governing the phenotypic expression of a series of transformation steps leading to the development of metastatic cancer Previous studies from this laboratory have identified a 7 fold down- regulation of the novel tumor suppressor Big-h3 among radiation induced tumorigenic BEP2D cells Furthermore ectopic re-expression of this gene suppresses tumorigenic phenotype and promotes the sensitivity of these tumor cells to etoposide-induced apoptosis To extend these studies using a genomically more stable bronchial cell line we ectopically expresses the catalytic subunit of telomerase hTERT in primary human small airway epithelial SAE cells and generated several clonal cell lines that have been continuously in culture for more than 250 population doublings and are considered immortal Comparably-treated control SAE cells infected with only the viral vector senesced after less than 10 population doublings The immortalized clones demonstrated anchorage dependent growth and are non-tumorigenic in nude mice These cells show no alteration in the p53 gene but a decrease in p16 expression Exponentially growing SAEh cells were exposed to graded doses of 1 GeV nucleon of 56 Fe ions accelerated at the Brookhaven National Laboratory Irradiated cells underwent gradual phenotypic alterations after extensive in vitro cultivation Transformed cells developed through a series of successive steps before becoming anchorage independent in semisolid medium These findings indicate

  4. Deletion of autophagy inducer RB1CC1 results in degeneration of the retinal pigment epithelium.

    Science.gov (United States)

    Yao, Jingyu; Jia, Lin; Khan, Naheed; Lin, Chengmao; Mitter, Sayak K; Boulton, Michael E; Dunaief, Joshua L; Klionsky, Daniel J; Guan, Jun-Lin; Thompson, Debra A; Zacks, David N

    2015-01-01

    Autophagy regulates cellular homeostasis and response to environmental stress. Within the retinal pigment epithelium (RPE) of the eye, the level of autophagy can change with both age and disease. The purpose of this study is to determine the relationship between reduced autophagy and age-related degeneration of the RPE. The gene encoding RB1CC1/FIP200 (RB1-inducible coiled-coil 1), a protein essential for induction of autophagy, was selectively knocked out in the RPE by crossing Best1-Cre mice with mice in which the Rb1cc1 gene was flanked with Lox-P sites (Rb1cc1(flox/flox)). Ex vivo and in vivo analyses, including western blot, immunohistochemistry, transmission electron microscopy, fundus photography, optical coherence tomography, fluorescein angiography, and electroretinography were performed to assess the structure and function of the retina as a function of age. Deletion of Rb1cc1 resulted in multiple autophagy defects within the RPE including decreased conversion of LC3-I to LC3-II, accumulation of autophagy-targeted precursors, and increased numbers of mitochondria. Age-dependent degeneration of the RPE occurred, with formation of atrophic patches, subretinal migration of activated microglial cells, subRPE deposition of inflammatory and oxidatively damaged proteins, subretinal drusenoid deposits, and occasional foci of choroidal neovascularization. There was secondary loss of photoreceptors overlying the degenerated RPE and reduction in the electroretinogram. These observations are consistent with a critical role of autophagy in the maintenance of normal homeostasis in the aging RPE, and indicate that disruption of autophagy leads to retinal phenotypes associated with age-related degeneration.

  5. Acute exposure to vibration is an apoptosis-inducing stimulus in the vocal fold epithelium.

    Science.gov (United States)

    Novaleski, Carolyn K; Kimball, Emily E; Mizuta, Masanobu; Rousseau, Bernard

    2016-10-01

    Clinical voice disorders pose significant communication-related challenges to patients. The purpose of this study was to quantify the rate of apoptosis and tumor necrosis factor-alpha (TNF-α) signaling in vocal fold epithelial cells in response to increasing time-doses and cycle-doses of vibration. 20 New Zealand white breeder rabbits were randomized to three groups of time-doses of vibration exposure (30, 60, 120min) or a control group (120min of vocal fold adduction and abduction). Estimated cycle-doses of vocal fold vibration were extrapolated based on mean fundamental frequency. Laryngeal tissue specimens were evaluated for apoptosis and gene transcript and protein levels of TNF-α. Results revealed that terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining was significantly higher after 120min of vibration compared to the control. Transmission electron microscopy (TEM) revealed no significant effect of time-dose on the mean area of epithelial cell nuclei. Extrapolated cycle-doses of vibration exposure were closely related to experimental time-dose conditions, although no significant correlations were observed with TUNEL staining or mean area of epithelial cell nuclei. TUNEL staining was positively correlated with TNF-α protein expression. Our findings suggest that apoptosis can be induced in the vocal fold epithelium after 120min of modal intensity phonation. In contrast, shorter durations of vibration exposure do not result in apoptosis signaling. However, morphological features of apoptosis are not observed using TEM. Future studies are necessary to examine the contribution of abnormal apoptosis to vocal fold diseases.

  6. Cadmium induced histopathology in the olfactory epithelium of a snakehead fish, Channa punctatus (Bloch

    Directory of Open Access Journals (Sweden)

    Debraj Roy

    2013-10-01

    Full Text Available Histopathology on the olfactory organ of a snakehead fish, Channa punctatus (Bloch, 1793 were assessed after exposing the fish to 2.5 mg/L and 5mg/L of CdCl2 for 15 days, 30 days and 45 days. Cellular organization of the epithelium was affected severely with degeneration of sensory and supporting cells and hyperplasia of basal cells and mucous cells. Mucous cell proliferation indicates the upregulation of mucous secretion to protect the epithelium from toxic effect of cadmium. The olfactory epithelium was endowed with the multipotent basal cells which differentiate into sensory cells, supporting cells and other cell types of the epithelium during normal cells turn over and in the event of cell death.  However, due to cadmium exposure proliferating basal cells failed to differentiate into normal cells and the undifferentiated proliferated cell formed lump and intraepithelial lesion altering the composition of the entire epithelium. Present study indicates that in prolonged exposure to cadmium chloride olfactory functions of the fish might be impaired due to loss of all sensory cells.

  7. Methoxychlor and estradiol induce oxidative stress DNA damage in the mouse ovarian surface epithelium.

    Science.gov (United States)

    Symonds, Daniel A; Merchenthaler, Istvan; Flaws, Jodi A

    2008-09-01

    Estrogenic compounds such as 17beta-estradiol (E(2)) and methoxychlor (MXC) induce oxidative stress damage in breast cells and mouse ovarian follicles, respectively. However, little is known about whether estrogenic compounds cause oxidative stress in the ovarian surface epithelium (OSE). Thus, this work tested the hypothesis that E(2) and MXC cause oxidative stress in the OSE. To test this hypothesis, we employed an improved mouse tissue culture assay in which OSE cells were treated with hydrogen peroxide (H2O2; positive control), MXC, or E(2) +/- the anti-oxidant vitamin E, or progesterone. The cells then were subjected to a novel direct immunofluorescent assay in which cells in the microtiter plate were reacted with antibodies that detect oxidative damage to DNA (8-hydroxy-2'-deoxyguanosine). The signal was identified with a tyramide Alexa Fluor fluorescent probe and quantified by microfluorimetry. Correction for cellularity was carried out for each well with a fluorescent DNA dye system (CyQuant) at a different wavelength. After 24 h, the mean Alexa Fluor CyQuant ratio was 11.3 +/- 0.9 for controls, 132 +/- 15 for H2O2 treated positive control cells (p < or = 0.01 from control), 105 +/- 6.6 for E(2) treated cells (p < or = 0.01 from control), and 64 +/- 5.1 for MXC-treated cells (p < or = 0.01 from control). After 72 h, the mean ratio was 121 +/- 10.6 for controls, 391 +/- 23 for H2O2 treated cells (p < or = 0.01 from control), 200 +/- 15 for E(2) treated cells (p < or = 0.03), and 228 +/- 21 for MXC-treated cells (p < or = 0.01). Further, vitamin E, but not progesterone, protected OSE cells from E(2)- and MXC-induced oxidative damage. This study demonstrates the feasibility of direct immunofluorescent quantitation of DNA adducts in cell cultures without DNA extraction. Moreover, these data indicate that E(2) and MXC produce oxidative DNA damage in the OSE, and that this damage is prevented by the anti-oxidant vitamin E.

  8. Early LPS-induced ERK activation in retinal pigment epithelium cells is dependent on PIP 2 -PLC.

    Science.gov (United States)

    Mateos, Melina V; Kamerbeek, Constanza B; Giusto, Norma M; Salvador, Gabriela A

    2016-06-01

    This article presents additional data regarding the study "The phospholipase D pathway mediates the inflammatory response of the retinal pigment epithelium" [1]. The new data presented here show that short exposure of RPE cells to lipopolysaccharide (LPS) induces an early and transient activation of the extracellular signal-regulated kinase (ERK1/2). This early ERK1/2 activation is dependent on phosphatidylinositol bisphosphate-phospholipase C (PIP2-PLC). On the contrary, neither the phospholipase D 1 (PLD1) nor the PLD2 inhibition is able to modulate the early ERK1/2 activation induced by LPS in RPE cells.

  9. TGF-β1 induced epithelial to mesenchymal transition (EMT in human bronchial epithelial cells is enhanced by IL-1β but not abrogated by corticosteroids

    Directory of Open Access Journals (Sweden)

    Zuraw Bruce L

    2009-10-01

    Full Text Available Abstract Background Chronic persistent asthma is characterized by ongoing airway inflammation and airway remodeling. The processes leading to airway remodeling are poorly understood, and there is increasing evidence that even aggressive anti-inflammatory therapy does not completely prevent this process. We sought to investigate whether TGFβ1 stimulates bronchial epithelial cells to undergo transition to a mesenchymal phenotype, and whether this transition can be abrogated by corticosteroid treatment or enhanced by the pro-inflammatory cytokine IL-1β. Methods BEAS-2B and primary normal human bronchial epithelial cells were stimulated with TGFβ1 and expression of epithelial and mesenchymal markers assessed by quantitative real-time PCR, immunoblotting, immunofluorescence microscopy and zymography. In some cases the epithelial cells were also incubated with corticosteroids or IL-1β. Results were analyzed using non-parametric statistical tests. Results Treatment of BEAS-2B or primary human bronchial epithelial cells with TGFβ1 significantly reduced the expression level of the epithelial adherence junction protein E-cadherin. TGFβ1 then markedly induced mesenchymal marker proteins such as collagen I, tenascin C, fibronectin and α-smooth muscle actin mRNA in a dose dependant manner. The process of mesenchymal transition was accompanied by a morphological change towards a more spindle shaped fibroblast cell type with a more motile and invasive phenotype. Corticosteroid pre-treatment did not significantly alter the TGFβ1 induced transition but IL-1β enhanced the transition. Conclusion Our results indicate, that TGFβ1 can induce mesenchymal transition in the bronchial epithelial cell line and primary cells. Since asthma has been strongly associated with increased expression of TGFβ1 in the airway, epithelial to mesenchymal transition may contribute to the contractile and fibrotic remodeling process that accompanies chronic asthma.

  10. Multiplexed quantitative high content screening reveals that cigarette smoke condensate induces changes in cell structure and function through alterations in cell signaling pathways in human bronchial cells.

    Science.gov (United States)

    Carter, Charleata A; Hamm, Jonathan T

    2009-07-10

    Human bronchial cells are one of the first cell types exposed to environmental toxins. Toxins often activate nuclear factor-kappaB (NF-kappaB) and protein kinase C (PKC). We evaluated the hypothesis that cigarette smoke condensate (CSC), the particulate fraction of cigarette smoke, activates PKC-alpha and NF-kappaB, and concomitantly disrupts the F-actin cytoskeleton, induces apoptosis and alters cell function in BEAS-2B human bronchial epithelial cells. Compared to controls, exposure of BEAS-2B cells to doses of 30mug/ml CSC significantly activated PKC-alpha, while CSC doses above 20mug/ml CSC significantly activated NF-kappaB. As NF-kappaB was activated, cell number decreased. CSC treatment of BEAS-2B cells induced a decrease in cell size and an increase in cell surface extensions including filopodia and lamellipodia. CSC treatment of BEAS-2B cells induced F-actin rearrangement such that stress fibers were no longer prominent at the cell periphery and throughout the cells, but relocalized to perinuclear regions. Concurrently, CSC induced an increase in the focal adhesion protein vinculin at the cell periphery. CSC doses above 30mug/ml induced a significant increase in apoptosis in BEAS-2B cells evidenced by an increase in activated caspase 3, an increase in mitochondrial mass and a decrease in mitochondrial membrane potential. As caspase 3 increased, cell number decreased. CSC doses above 30mug/ml also induced significant concurrent changes in cell function including decreased cell spreading and motility. CSC initiates a signaling cascade in human bronchial epithelial cells involving PKC-alpha, NF-kappaB and caspase 3, and consequently decreases cell spreading and motility. These CSC-induced alterations in cell structure likely prevent cells from performing their normal function thereby contributing to smoke-induced diseases.

  11. Probiotic-induced changes in the intestinal epithelium: implications in gastrointestinal disease.

    Science.gov (United States)

    Ramakrishna, B S

    2009-01-01

    There is resurgent interest in the use of probiotics to maintain gastrointestinal and systemic health, driven by recent advances in knowledge of bacterial interactions with the epithelium and innate immune system of the intestine. The effects of probiotic bacteria on the intestinal epithelium and their downstream consequences are reviewed. Probiotics prevent pathogen adherence and invasion of the epithelium, partly by blocking adherence sites but also by upregulating gene expression of MUC2 and of antimicrobial peptides. Metabolic effects of probiotics on the intestinal epithelium include production of short chain fatty acids which influence epithelial cell metabolism, turnover and apoptosis. Bacterial metabolism of unabsorbed dietary constituents with production of free radicals and phenolic metabolites can lead to DNA damage and cancer; probiotics restore eubiosis and potentially prevent this. Probiotics alter expression and redistribution of tight junction proteins and reduce intestinal permeability limiting absorption of noxious molecules from the gut lumen. Most studied are the effects of probiotics on epithelial cells which are the first line of innate immune-capable cells that encounter luminal flora. Probiotics, through secreted molecules, influence the innate inflammatory response of epithelial cells to stimuli from the gut lumen, and reduce mucosal inflammation. Through effects on dendritic, and possibly epithelial, cells they influence naïve T cells in the lamina propria of the gut and thus influence adaptive immunity. These varied effects of probiotics have implications for the treatment of several gastrointestinal diseases including antibiotic-associated colitis, acute gastroenteritis, inflammatory bowel disease, colon cancer, and irritable bowel syndrome.

  12. Repair of tracheal epithelium by basal cells after chlorine-induced injury

    Directory of Open Access Journals (Sweden)

    Musah Sadiatu

    2012-11-01

    Full Text Available Abstract Background Chlorine is a widely used toxic compound that is considered a chemical threat agent. Chlorine inhalation injures airway epithelial cells, leading to pulmonary abnormalities. Efficient repair of injured epithelium is necessary to restore normal lung structure and function. The objective of the current study was to characterize repair of the tracheal epithelium after acute chlorine injury. Methods C57BL/6 mice were exposed to chlorine and injected with 5-ethynyl-2′-deoxyuridine (EdU to label proliferating cells prior to sacrifice and collection of tracheas on days 2, 4, 7, and 10 after exposure. Airway repair and restoration of a differentiated epithelium were examined by co-localization of EdU labeling with markers for the three major tracheal epithelial cell types [keratin 5 (K5 and keratin 14 (K14 for basal cells, Clara cell secretory protein (CCSP for Clara cells, and acetylated tubulin (AcTub for ciliated cells]. Morphometric analysis was used to measure proliferation and restoration of a pseudostratified epithelium. Results Epithelial repair was fastest and most extensive in proximal trachea compared with middle and distal trachea. In unexposed mice, cell proliferation was minimal, all basal cells expressed K5, and K14-expressing basal cells were absent from most sections. Chlorine exposure resulted in the sloughing of Clara and ciliated cells from the tracheal epithelium. Two to four days after chlorine exposure, cell proliferation occurred in K5- and K14-expressing basal cells, and the number of K14 cells was dramatically increased. In the period of peak cell proliferation, few if any ciliated or Clara cells were detected in repairing trachea. Expression of ciliated and Clara cell markers was detected at later times (days 7–10, but cell proliferation was not detected in areas in which these differentiated markers were re-expressed. Fibrotic lesions were observed at days 7–10 primarily in distal trachea. Conclusion

  13. Human bronchial epithelial BEAS-2B cells, an appropriate in vitro model to study heavy metals induced carcinogenesis

    Science.gov (United States)

    Park, Youn-hee; Kim, Donghern; Dai, Jin; Zhang, Zhuo

    2015-01-01

    Occupational and environmental exposure to arsenic (III) and chromium VI (Cr(VI)) have been confirmed to cause lung cancer. Mechanisms of these metals-induced carcinogenesis are still under investigation. Selection of cell lines to be used is essential for the mechanistic studies. Human bronchial epithelial BEAS-2B cells are the cells to be utilized by most of scientists. However, due to p53 missense mutation (CCG → TCG) at codon 47 and the codon 72 polymorphism (CGC → CCC) in BEAS-2B cells, its usage has frequently been questioned. The present study has examined activity and expression of 53 and its downstream target protein p21 upon acute or chronic exposure of BEAS-2B cells to arsenic and Cr(VI). The results show that short-term exposure of BEAS-2B cells to arsenic or Cr(VI) was able to activate both p53 and p21. Chronic exposure of BEAS-2B cells to these two metals caused malignant cell transformation and tumorigenesis. In arsenic-transformed BEAS-2B cells reductions in p53 promoter activity, mRNA expression, and phosphorylation of p53 at Ser392 were observed, while the total p53 protein level remained the same compared to those in passage-matched parent ones. p21 promoter activity and expression were decreased in arsenic-transformed cells. Cr(VI)-transformed cells exhibit elevated p53 promoter activity, mRNA expression, and phosphorylation at Ser15, but reduced phosphorylation at Ser392 and total p53 protein level compared to passage-matched parent ones. p21 promoter activity and expression were elevated in Cr(VI)-transformed cells. These results demonstrate that p53 is able to respond to exposure of arsenic or Cr(VI), suggesting that BEAS-2B cells are an appropriate in vitro model to investigate arsenic or Cr(VI) induced lung cancer. PMID:26091798

  14. Trans, trans-2,4-decadienal induced cell proliferation via p27 pathway in human bronchial epithelial cells.

    Science.gov (United States)

    Chang, Yun-Ching; Lin, Pinpin

    2008-04-01

    Lung cancer is the leading cause of cancer deaths worldwide. Epidemiological studies have shown that exposure to cooking oil fumes (COF) is a risk factor for lung cancer. Trans, trans-2,4-decadienal (tt-DDE), a dienaldehyde, is abundant in heated oils and COF. Previously, we found that long-term exposure (45 days) to a sub-lethal dose (1 microM) of tt-DDE significantly increased growth of human bronchial epithelial cells (BEAS-2B). Aims of this study are to understand the mechanism of tt-DDE-induced cell proliferation and possible protective effects of antioxidant, vitamin C and N-acetylcysteine (NAC) in BEAS-2B cells. Utilizing the real-time RT-PCR and Western immunoblotting, we found that p27 mRNA and protein levels were significantly increased by 1 microM tt-DDE treatment. Co-treatment with vitamin C or NAC partially prevented tt-DDE-induced cell proliferation. In addition, the downstream targets of p27, including CDK4, cyclin D1 and phosphorylated-Rb proteins, increased in 1 microM tt-DDE-treated cells and these changes were prevented by NAC co-treatment. Therefore, these results suggest that tt-DDE increased cell proliferation via inhibition of p27 expression, increase in CDK4/cyclin D1 protein accumulation and enhancement of Rb phosphorylation. Increased cell proliferation is considered as the early stages of lung carcinogenesis. Administration of antioxidants may prevent COF-associated lung carcinogenesis.

  15. Role of reactive oxygen species in arsenic-induced transformation of human lung bronchial epithelial (BEAS-2B) cells

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Zhuo, E-mail: zhuo.zhang@uky.edu [Graduate Center for Toxicology, University of Kentucky, Lexington, KY 40536 (United States); Pratheeshkumar, Poyil; Budhraja, Amit; Son, Young-Ok [Center for Research on Environmental Diseases, University of Kentucky, Lexington, KY 40536 (United States); Kim, Donghern [Graduate Center for Toxicology, University of Kentucky, Lexington, KY 40536 (United States); Shi, Xianglin [Center for Research on Environmental Diseases, University of Kentucky, Lexington, KY 40536 (United States)

    2015-01-09

    Highlights: • Short term exposure of cells to arsenic causes ROS generation. • Chronical exposure of cells to arsenic causes malignant cell transformation. • Inhibition of ROS generation reduces cell transformation by arsenic. • Arsenic-transformed cells exhibit reduced capacity of generating ROS. • Arsenic-transformed cells exhibit increased levels of antioxidants. - Abstract: Arsenic is an environmental carcinogen, its mechanisms of carcinogenesis remain to be investigated. Reactive oxygen species (ROS) are considered to be important. A previous study (Carpenter et al., 2011) has measured ROS level in human lung bronchial epithelial (BEAS-2B) cells and arsenic-transformed BEAS-2B cells and found that ROS levels were higher in transformed cells than that in parent normal cells. Based on these observations, the authors concluded that cell transformation induced by arsenic is mediated by increased cellular levels of ROS. This conclusion is problematic because this study only measured the basal ROS levels in transformed and parent cells and did not investigate the role of ROS in the process of arsenic-induced cell transformation. The levels of ROS in arsenic-transformed cells represent the result and not the cause of cell transformation. Thus question concerning whether ROS are important in arsenic-induced cell transformation remains to be answered. In the present study, we used expressions of catalase (antioxidant against H{sub 2}O{sub 2}) and superoxide dismutase 2 (SOD2, antioxidant against O{sub 2}{sup ·−}) to decrease ROS level and investigated their role in the process of arsenic-induced cell transformation. Our results show that inhibition of ROS by antioxidant enzymes decreased arsenic-induced cell transformation, demonstrating that ROS are important in this process. We have also shown that in arsenic-transformed cells, ROS generation was lower and levels of antioxidants are higher than those in parent cells, in a disagreement with the previous

  16. Differential Expression of pro-inflammatory and oxidative stress mediators induced by nitrogen dioxide and ozone in primary human bronchial epithelial cells

    Science.gov (United States)

    CONTEXT: N02 and 03 are ubiquitous air toxicants capable of inducing lung damage to the respiratory epithelium. Due to their oxidizing capabilities, these pollutants have been proposed to target specific biological pathways, but few publications have compared the pathways activat...

  17. HO-1 inhibits IL-13-induced goblet cell hyperplasia associated with CLCA1 suppression in normal human bronchial epithelial cells.

    Science.gov (United States)

    Mishina, Kei; Shinkai, Masaharu; Shimokawaji, Tadasuke; Nagashima, Akimichi; Hashimoto, Yusuke; Inoue, Yoriko; Inayama, Yoshiaki; Rubin, Bruce K; Ishigatsubo, Yoshiaki; Kaneko, Takeshi

    2015-12-01

    Mucus hypersecretion and goblet cell hyperplasia are common features that characterize asthma. IL-13 increases mucin (MUC) 5AC, the major component of airway mucus, in airway epithelial cells. According to the literature, IL-13 receptor activation leads to STAT6 activation and consequent induction of chloride channel accessory 1 (CLCA1) gene expression, associated with the induction of MUC5AC. Heme oxygenase-1 (HO-1) is an enzyme that catalyzes oxidation of heme to biliverdin, and has anti-inflammatory and anti-oxidant properties. We examined the effects of HO-1 on mucin production and goblet cell hyperplasia induced by IL-13. Moreover, we assessed the cell signaling intermediates that appear to be responsible for mucin production. Normal human bronchial epithelial (NHBE) cells were grown at air liquid interface (ALI) in the presence or absence of IL-13 and hemin, a HO-1 inducer, for 14 days. Protein concentration was analyzed using ELISA, and mRNA expression was examined by real-time PCR. Histochemical analysis was performed using HE staining, andWestern blotting was performed to evaluate signaling transduction pathway. Hemin (4 μM) significantly increased HO-1 protein expression (p b 0.01) and HO-1 mRNA expression (p b 0.001). IL-13 significantly increased goblet cells, MUC5AC protein secretion (p b 0.01) and MUC5AC mRNA (p b 0.001), and these were decreased by hemin by way of HO-1. Tin protoporphyrin (SnPP)-IX, a HO-1 inhibitor, blocked the effect of hemin restoring MUC5AC protein secretion (p b 0.05) and goblet cell hyperplasia. Hemin decreased the expression of CLCA1 mRNA (p b 0.05) and it was reversed by SnPP-IX, but could not suppress IL-13-induced phosphorylation of STAT6 or SAM pointed domain-containing ETS transcription factor (SPDEF) and Forkhead box A2 (FOXA2) mRNA expression. In summary, HO-1 overexpression suppressed IL-13-induced goblet cell hyperplasia and MUC5AC production, and involvement of CLCA1 in the mechanism was suggested.

  18. Spectral Karyotyping Detects Chromosome Damage in Bronchial Cells of Smokers and Patients with Cancer

    OpenAIRE

    Varella-Garcia, Marileila; Chen, Lin; Powell, Roger L.; Hirsch, Fred R.; Kennedy, Timothy C.; Keith, Robert; Miller, York E.; Mitchell, John D; Franklin, Wilbur A.

    2007-01-01

    Rationale: Lung cancer is a multistep process that is preceded and often accompanied by molecular cytogenetic lesions in benign bronchial epithelium, the precise character, extent and timing of which are not well defined.

  19. ORGANIC AND INORGANIC ARSENICALS SENSITIZE HUMAN BRONCHIAL EPITHELIAL CELLS TO HYDROGEN PEROXIDE-INDUCED DNA DAMAGE

    Science.gov (United States)

    The lungs are a target organ for arsenic carcinogenesis, however, its mechanism of action remains unclear. Furthermore, it has been suggested that inorganic arsenic (iAs) can potentiate DNA damage induced by other agents. Once inside the human body iAs generally undergoes two ...

  20. s-Ethyl Cysteine and s-Methyl Cysteine Protect Human Bronchial Epithelial Cells Against Hydrogen Peroxide Induced Injury.

    Science.gov (United States)

    Hsia, Te-chun; Yin, Mei-chin

    2015-09-01

    Protective effects and actions from s-ethyl cysteine (SEC) and s-methyl cysteine (SMC) for BEAS-2B cells were examined. BEAS-2B cells were pretreated with SEC or SMC at 4, 8, or 16 μmol/L, and followed by hydrogen peroxide (H2 O2 ) treatment. Data showed that H2 O2 enhanced Bax, caspase-3 and caspase-8 expression, and declined Bcl-2 expression. However, SEC or SMC dose-dependently decreased caspase-3 expression and reserved Bcl-2 expression. H2 O2 increased reactive oxygen species (ROS) production, and lowered glutathione level, glutathione peroxide, and glutathione reductase activities in BEAS-2B cells. SEC or SMC pretreatments reduced ROS generation, and maintained glutathione redox cycle in those cells. H2 O2 upregulated the expression of both p47(phox) and gp91(phox) . SEC and SMC downregulated p47(phox) expression. SEC or SMC at 8 and 16 μmol/L decreased H2 O2 -induced release of inflammatory cytokines. H2 O2 stimulated the activation of nuclear factor-κB (NF-κB) and mitogen-activated protein kinase. SEC and SMC pretreatments dose-dependently downregulated NF-κB p65 and p-p38 expression. Pyrrolidine dithiocarbamate or SB203580 inhibited NF-κB activation and p38 phosphorylation; thus, SEC or SMC pretreatments failed to affect protein expression of these factors. These novel findings suggest that SEC or SMC could protect bronchial cells and benefit respiratory epithelia stability and functions.

  1. Repeatability of and relationship between potential COPD biomarkers in bronchoalveolar lavage, bronchial biopsies, serum, and induced sputum.

    Directory of Open Access Journals (Sweden)

    Stefan Röpcke

    Full Text Available Chronic Obstructive Pulmonary Disease (COPD is a chronic inflammatory disease, primarily affecting the airways. Stable biomarkers characterizing the inflammatory phenotype of the disease, relevant for disease activity and suited to predict disease progression are needed to monitor the efficacy and safety of drug interventions. We therefore analyzed a large panel of markers in bronchoalveolar lavage, bronchial biopsies, serum and induced sputum of 23 healthy smokers and 24 smoking COPD patients (GOLD II matched for age and gender. Sample collection was performed twice within a period of 6 weeks. Assays for over 100 different markers were validated for the respective matrices prior to analysis. In our study, we found 51 markers with a sufficient repeatability (intraclass correlation coefficient >0.6, most of these in serum. Differences between groups were observed for markers from all compartments, which extends (von-Willebrand-factor and confirms (e.g. C-reactive-protein, interleukin-6 previous findings. No correlations between lung and serum markers were observed, including A1AT. Airway inflammation defined by sputum neutrophils showed only a moderate repeatability. This could be improved, when a combination of neutrophils and four sputum fluid phase markers was used to define the inflammatory phenotype.In summary, our study provides comprehensive information on the repeatability and interrelationship of pulmonary and systemic COPD-related markers. These results are relevant for ongoing large clinical trials and future COPD research. While serum markers can discriminate between smokers with and without COPD, they do not seem to sufficiently reflect the disease-associated inflammatory processes within the airways.

  2. NGF is an essential survival factor for bronchial epithelial cells during respiratory syncytial virus infection.

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    Sreekumar Othumpangat

    Full Text Available Overall expression of neurotrophins in the respiratory tract is upregulated in infants infected by the respiratory syncytial virus (RSV, but it is unclear where (structural vs. inflammatory cells, upper vs. lower airways and why, these changes occur. We analyzed systematically the expression of neurotrophic factors and receptors following RSV infection of human nasal, tracheal, and bronchial epithelial cells, and tested the hypothesis that neurotrophins work as innate survival factors for infected respiratory epithelia.Expression of neurotrophic factors (nerve growth factor, NGF; brain-derived neurotrophic factor, BDNF and receptors (trkA, trkB, p75 was analyzed at the protein level by immunofluorescence and flow cytometry and at the mRNA level by real-time PCR. Targeted siRNA was utilized to blunt NGF expression, and its effect on virus-induced apoptosis/necrosis was evaluated by flow cytometry following annexin V/7-AAD staining.RSV infection was more efficient in cells from more distal (bronchial vs. more proximal origin. In bronchial cells, RSV infection induced transcript and protein overexpression of NGF and its high-affinity receptor trkA, with concomitant downregulation of the low-affinity p75(NTR. In contrast, tracheal cells exhibited an increase in BDNF, trkA and trkB, and nasal cells increased only trkA. RSV-infected bronchial cells transfected with NGF-specific siRNA exhibited decreased trkA and increased p75(NTR expression. Furthermore, the survival of bronchial epithelial cells was dramatically decreased when their endogenous NGF supply was depleted prior to RSV infection.RSV infection of the distal airway epithelium, but not of the more proximal sections, results in overexpression of NGF and its trkA receptor, while the other p75(NTR receptor is markedly downregulated. This pattern of neurotrophin expression confers protection against virus-induced apoptosis, and its inhibition amplifies programmed cell death in the infected

  3. Toll-like receptor 2 is upregulated by hog confinement dust in an IL-6 dependent manner in the airway epithelium

    OpenAIRE

    Bailey, KL; Poole, JA; Mathisen, TL; Wyatt, TA; Von Essen, SG; Romberger, DJ

    2008-01-01

    Hog confinement workers are at high risk to develop chronic bronchitis as a result of their exposure to organic dust. Chronic bronchitis is characterized by inflammatory changes of the airway epithelium. A key mediator in inflammation is Toll-like receptor 2 (TLR2). We investigated the role of TLR2 in pulmonary inflammation induced by hog confinement dust. Normal Human Bronchial Epithelial Cells (NHBE) were grown in culture and exposed to hog confinement dust extract. Hog confinement dust upr...

  4. Smad Molecules Expression Pattern in Human Bronchial Airway Induced by Sulfur Mustard

    Directory of Open Access Journals (Sweden)

    Maryam Adelipour

    2011-09-01

    Full Text Available Airway remodelling is characterized by the thickening and reorganization of the airways seen in mustard  lung patients. Mustard lung is the  general description  for  the  chronic obstructive  pulmonary  disease induced  by  sulfur  mustard(SM. Pulmonary  disease was diagnosed as the most important  disorder in individuals that had been exposed to sulfur mustard. Sulfur mustard is a chemical warfare agent developed during Wars. Iraqi forces frequently used it against Iranian during Iran –Iraq in the 1980–1988. Peribronchial fibrosis result  from  airway remodeling  that  include  excess  of  collagen of  extracellular matrix deposition  in  the  airway wall. Some of  Smads families in  association with TGF-β  are involved in airway remodeling due to lung fibrosis. In the present study we compared the mRNA expression of Smad2, Smad3, and Smad4 and Smad7 genes in airway wall biopsies of chemical-injured patients with non-injured patients as control.We used airway wall biopsies of ten unexposed patients and fifteen SM-induced patients. Smads expression was evaluated by RT-PCR followed by bands densitometry.Expression levels of Smad3 and Smad4 in SM exposed patients were upregulated but Smad2 and Smad7 was not significantly altered.Our results revealed that Smad3, and 4 may be involved in airway remodeling process in SM induced  patients  by  activation of  TGF-β.  Smad pathway is  the  most  represented signaling mechanism for  airway remodeling and  peribronchial fibrosis. The  complex of Smads in the nucleus affects a series of genes that results in peribronchial fibrosis in SM- induced patients.

  5. The inhibitive effects of gefinitib on the airway epithelium remodeling of bronchial asthma in mice%吉非替尼对哮喘小鼠模型气道上皮重塑抑制作用的研究

    Institute of Scientific and Technical Information of China (English)

    宋娇; 马战平; 刘大鹏; 杨学敏; 宋立强

    2015-01-01

    Objective:To evaluate the treatment effects of gefinitib ,a selective Epidermal growth factor re‐ceptor (EGFR) tyrosine kinase inhibitor ,on the airway remodeling in asthmatic mice .Methods :BALB/c mice were randomly divided into a sham‐challenged asthmatic group ,an asthma group ,a gefinitib prevention group (prevention group) ,and a gefinitib treatment group (treatment group) .HE staining detected the inflammatory lesions of lung tissues and the proliferation of airway epithelium in mice of all groups .PAS staining detected the cell counting and mucus secretion of airway goblet cells in mice of all groups .TUNEL method detected apoptosis of lung tissues in mice of all groups .Western blot method was used to detecte p‐EGFR and EGFR protein expression of lung tissues in mice of all groups .Results:Compared with the sham‐challenged asthmatic group ,there were more significant in‐flammatory lesions of lung tissues ,increasing numbers of airway goblet cells in mice of asthma group .These patho‐logical change were improved in mice of both prevention group and treatment group and especially in the prevention group (P0 .05) .Conclusion:Gefinitib have some protective effects on airway epithelium remodeling of asthmatic mice ,and its mechanism may be blocking the EGFR signaling and inducing the apoptosis of asthma airway epithelial cells .%目的:观察选择性表皮生长因子受体(EGFR)酪氨酸激酶抑制剂吉非替尼对哮喘小鼠气道上皮重塑的影响。方法:将BALB/c小鼠随机分为正常对照组、哮喘组、吉非替尼预防组(预防组)、吉非替尼治疗组(治疗组)。苏木精‐伊红染色法、过碘酸‐雪夫特殊染色法、原位末端转移酶标记法分别检测各组小鼠气道中炎症细胞浸润水平、杯状细胞数量及上皮细胞凋亡等指标,Western blot法检测各组小鼠肺组织中p‐EGFR、EGFR蛋白含量的变化。结果:与正常对照组相比,哮喘组小鼠出

  6. THE EFFECT OF NEDOCROMIL SODIUM ON THE EARLY AND LATE REACTION AND ALLERGEN-INDUCED BRONCHIAL HYPERRESPONSIVENESS

    NARCIS (Netherlands)

    AALBERS, R; KAUFFMAN, HF; GROEN, H; KOETER, GH; DEMONCHY, JGR

    1991-01-01

    Bronchial hyperresponsiveness (BHR) to methacholine was studied in 14 patients with asthma and five healthy control subjects, with and without pretreatment with nedocromil sodium, 3 and 24 hours after allergen challenge. Eleven patients demonstrated a dual asthmatic response. A significant decrease

  7. Zinc Induced G2/M Blockage is p53 and p21 Dependent in Normal Human Bronchial Epithelial Cells

    Science.gov (United States)

    The involvement of the p53 and p21 signal pathway in the G2/M cell cycle progression of zinc supplemented normal human bronchial epithelial (NHBE) cells was examined using the siRNA approach. Cells were cultured for one passage in different concentrations of zinc: <0.4 microM (ZD) as zinc-deficient;...

  8. TNF-like weak inducer of apoptosis (TWEAK promotes beta cell neogenesis from pancreatic ductal epithelium in adult mice.

    Directory of Open Access Journals (Sweden)

    Fei Wu

    Full Text Available AIM/HYPOTHESIS: The adult mammalian pancreas has limited ability to regenerate in order to restore adequate insulin production from multipotent progenitors, the identity and function of which remain poorly understood. Here we test whether the TNF family member TWEAK (TNF-like weak inducer of apoptosis promotes β-cell neogenesis from proliferating pancreatic ductal epithelium in adult mice. METHODS: C57Bl/6J mice were treated with Fc-TWEAK and pancreas harvested at different time points for analysis by histology and immunohistochemistry. For lineage tracing, 4 week old double transgenic mice CAII-CreER(TM: R26R-eYFP were implanted with tamoxifen pellet, injected with Fc-TWEAK or control Ig twice weekly and analyzed at day 18 for TWEAK-induced duct cell progeny by costaining for insulin and YFP. The effect of TWEAK on pancreatic regeneration was determined by pancytokeratin immunostaining of paraffin embedded sections from wildtype and TWEAK receptor (Fn14 deficient mice after Px. RESULTS: TWEAK stimulates proliferation of ductal epithelial cells through its receptor Fn14, while it has no mitogenic effect on pancreatic α- or β-cells or acinar cells. Importantly, TWEAK induces transient expression of endogenous Ngn3, a master regulator of endocrine cell development, and induces focal ductal structures with characteristics of regeneration foci. In addition, we identify by lineage tracing TWEAK-induced pancreatic β-cells derived from pancreatic duct epithelial cells. Conversely, we show that Fn14 deficiency delays formation of regenerating foci after Px and limits their expansion. CONCLUSIONS/INTERPRETATION: We conclude that TWEAK is a novel factor mediating pancreatic β-cell neogenesis from ductal epithelium in normal adult mice.

  9. Recent H1N1 viruses (A/USSR/90/77, A/Fiji/15899/83, A/Firenze/13/83) replicate poorly in ferret bronchial epithelium. Brief report.

    Science.gov (United States)

    Sweet, C; Bird, R A; Coates, D M; Overton, H A; Smith, H

    1985-01-01

    Three recent wild-type H1N1 influenza virus isolates (A/USSR/90/77, A/Fiji/15899/83 and A/Firenze/13/83) replicated poorly in organ cultures of ferret bronchial tissue compared with the replication of an H3N2 wild-type virus (A/England/939/69). All four viruses replicated well in nasal turbinate tissue. Examination of one H1N1 virus (A/USSR/90/77) in vivo showed heavy infection in the upper respiratory tract of ferrets but little in the lower respiratory tract. These results raise the possibility that the mildness of human influenza arising from the H1N1 strains may be due to lack of capacity to attack the lower respiratory tract as well as the presence of antibody in previously exposed persons.

  10. Influence of sensitization and allergen provocation procedures on the development of allergen-induced bronchial hyperreactivity in conscious, unrestrained guinea-pigs

    Directory of Open Access Journals (Sweden)

    R. E. Santing

    1995-01-01

    Full Text Available The effects of different sensitization and allergen provocation regimens on the development of allergen-induced bronchial hyperreactivity (BHR to histamine were investigated in conscious, unrestrained guinea-pigs. Similar early and late phase asthmatic reactions, BHR for inhaled histamine after the early (6 h as well as after the late reaction (24 h, and airway inflammation were observed after a single allergen provocation in animals sensitized to produce mainly IgG or IgE antibodies, respectively. Repeating the allergen provocation in the IgE-sensitized animals after 7 days, using identical provocation conditions, resulted in a similar development of BHR to histamine inhalation. Repetition of the allergen provocation during 4 subsequent days resulted in a decreased development of BHR after each provocation, despite a significant increase in the allergen provocation dose necessary to obtain similar airway obstruction. The number of inflammatory cells in the bronchoalveolar lavage was not significantly changed after repeated provocation, when compared with a single allergen provocation. Finally, we investigated allergen-induced bronchial hyperreactivity by repetition of the sensitization procedure at day 7 and 14 (booster, followed by repeated allergen provocation twice a week for 5 weeks. Surprisingly, no BHR to histamine could be observed after either provocation, while the number of inflammatory cells in the bronchoalveolar lavage fluid after 5 weeks was enhanced compared with controls. These data indicate that both IgE and IgG sensitized guinea-pigs may develop bronchial hyperreactivity after a single allergen provocation. Repeated allergen exposure of IgE sensitized animals causes a gradual fading of the induced hyperreactivity despite the on-going presence of inflammatory cells in the airways, indicating a mechanism of reduced cellular activation.

  11. Primary mechanism of the role of dual oxidase-1 causing airway allergic diseases in human bronchial epithelium%双重氧化酶1引起变应性疾病发生机制的初步研究

    Institute of Scientific and Technical Information of China (English)

    王丽芬; 黄志纯; 吴修法; 王海飞

    2013-01-01

    能依赖于脂筏来源的神经酰胺.%Objective To investigate the role of dual oxidase-1 (DUOX-1) inducing airway hyperresponsiveness in human bronchial epithelium.Methods The human bronchial epithelial cells were divided into several groups:control group,tumor necrosis factor-α (TNF-α) group,methyl-β-cyclodextrin (M-β-CD) + TNF-α group,desipramine (DES) + TNF-α group,diphenylene iodonium (DPI) + TNF-α group and apocynin (APO) + TNF-α group.Fractionation was performed by sucrose gradient centrifugation and the protein DUOX-1 was measured by western blotting.The lipid raft clusters and its colocalization with DUOX-1 were confocal analysed.The intracellular reactive oxygen species (ROS) accumulation was measured by fluorescence of reactive oxygen probe of intracellular measurement.Sigmastat 3.02 software was used to analyze the data.Results (1) Detection of ROS,control group:1.00± 0.00 ; TNF-α group:1.95± 0.16 ; M-β-CD + TNF-α group:0.91 ± 0.16 ; DES + TNF-α group:1.49± 0.20 ; DPI + TNF-α group:1.03 ± 0.16 ; APO + TNF-α group:1.47 ± 0.26.The difference was statistically significant (F =3.83,P <0.05).(2) Extracts in rafts to lipid rafts region represents the ratio of total protein,protein content DUOX-1each group,control group:0.21 ± 0.02; TNF-α group:0.49 ± 0.04; M-β-CD + TNF-α group:0.08 ±0.02 ; DES + TNF-α group:0.09 ± 0.03 ; the difference was statistically significant (F =3.96,P < 0.05).(3) DUOX-1 protein fluorescence values,control group:1.72 ± 0.21; TNF-α group:8.11 ± 1.23; M-β-CD + TNF-α group:1.51 ± 0.32; DES + TNF-α group:1.43 ± 0.11 ; the difference was statistically significant (F =4.87,P < 0.05).(4) DUOX-1 gene detection,control group:1.00 ± 0.00 ScrRNA +TNF-α group:1.75 ± 0.04; DUOX-1siRNA + TNF-αgroup:1.15 ± 0.02; the difference was statistically significant (F =4.19,P < 0.05).Conclusion TNF-α can induce DUOX-1 expression increasing in lipid raft,then the DUOX-1 can be activated to increase reactive

  12. Estradiol increases mucus synthesis in bronchial epithelial cells.

    Directory of Open Access Journals (Sweden)

    Anthony Tam

    Full Text Available Airway epithelial mucus hypersecretion and mucus plugging are prominent pathologic features of chronic inflammatory conditions of the airway (e.g. asthma and cystic fibrosis and in most of these conditions, women have worse prognosis compared with male patients. We thus investigated the effects of estradiol on mucus expression in primary normal human bronchial epithelial cells from female donors grown at an air liquid interface (ALI. Treatment with estradiol in physiological ranges for 2 weeks caused a concentration-dependent increase in the number of PAS-positive cells (confirmed to be goblet cells by MUC5AC immunostaining in ALI cultures, and this action was attenuated by estrogen receptor beta (ER-β antagonist. Protein microarray data showed that nuclear factor of activated T-cell (NFAT in the nuclear fraction of NHBE cells was increased with estradiol treatment. Estradiol increased NFATc1 mRNA and protein in ALI cultures. In a human airway epithelial (1HAE0 cell line, NFATc1 was required for the regulation of MUC5AC mRNA and protein. Estradiol also induced post-translational modification of mucins by increasing total fucose residues and fucosyltransferase (FUT-4, -5, -6 mRNA expression. Together, these data indicate a novel mechanism by which estradiol increases mucus synthesis in the human bronchial epithelium.

  13. Human bronchial epithelial BEAS-2B cells, an appropriate in vitro model to study heavy metals induced carcinogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Park, Youn-hee; Kim, Donghern; Dai, Jin; Zhang, Zhuo, E-mail: zhuo.zhang@uky.edu

    2015-09-15

    Occupational and environmental exposure to arsenic (III) and chromium VI (Cr(VI)) have been confirmed to cause lung cancer. Mechanisms of these metals carcinogenesis are still under investigation. Selection of cell lines to be used is essential for the studies. Human bronchial epithelial BEAS-2B cells are the cells to be utilized by most of scientists. However, due to p53 missense mutation (CCG → TCG) at codon 47 and the codon 72 polymorphism (CGC → CCC) in BEAS-2B cells, its usage has frequently been questioned. The present study has examined activity and expression of 53 and its downstream target protein p21 upon acute or chronic exposure of BEAS-2B cells to arsenic and Cr(VI). The results show that short-term exposure of BEAS-2B cells to arsenic or Cr(VI) was able to activate both p53 and p21. Chronic exposure of BEAS-2B cells to these two metals caused malignant cell transformation and tumorigenesis. In arsenic-transformed BEAS-2B cells reductions in p53 promoter activity, mRNA expression, and phosphorylation of p53 at Ser392 were observed, while the total p53 protein level remained the same compared to those in passage-matched parent ones. p21 promoter activity and expression were decreased in arsenic-transformed cells. Cr(VI)-transformed cells exhibit elevated p53 promoter activity, mRNA expression, and phosphorylation at Ser15, but reduced phosphorylation at Ser392 and total p53 protein level compared to passage-matched parent ones. p21 promoter activity and expression were elevated in Cr(VI)-transformed cells. These results demonstrate that p53 is able to respond to exposure of arsenic or Cr(VI), suggesting that BEAS-2B cells are an appropriate in vitro model to investigate arsenic or Cr(VI) induced lung cancer. - Highlights: • Short-term exposure of BEAS-2B cells to arsenic or Cr(VI) activates p53 and p21. • Chronic exposure of BEAS-2B cells to arsenic or Cr(VI) causes cell transformation and tumorigenesis. • Arsenic-transformed cells exhibit

  14. Spontaneous and cytokine induced expression and activity of matrix metalloproteinases in human colonic epithelium

    DEFF Research Database (Denmark)

    Pedersen, G; Saermark, T; Kirkegaard, T;

    2009-01-01

    for MMP cleavage. HT-29 and DLD-1 expressed several MMPs and levels of MMP-3, -10 and -13 mRNA expression were increased significantly by tumour necrosis factor (TNF)-alpha exposure. Transcripts of MMP-1, -3, -7, -9, -10 and -12 were detected in CECs and all, except MMP12, at significantly increased...... levels in cells from inflamed IBD mucosa. MMP-2 and -8 mRNA were expressed inconsistently and MMP-11, -13 and -14 mRNA undetectable. Proteolytic MMP activity was detected in CEC supernatants and the level was increased significantly in inflamed IBD epithelium. The enzyme activity was inhibited strongly...... by a specific MMP inhibitor (GM 6001). A significant TNF-alpha-mediated increase in MMP enzyme activity was also detected in HT-29 cells in vitro. In conclusion, the expression of several MMPs as well as the level of functional MMPactivity is increased in CEC from patients with active IBD. The results suggest...

  15. Salinity-induced regulation of the myo-inositol biosynthesis pathway in tilapia gill epithelium.

    Science.gov (United States)

    Sacchi, Romina; Li, Johnathon; Villarreal, Fernando; Gardell, Alison M; Kültz, Dietmar

    2013-12-15

    The myo-inositol biosynthesis (MIB) pathway converts glucose-6-phosphate to the compatible osmolyte myo-inositol that protects cells from osmotic stress. Using proteomics, the enzymes that constitute the MIB pathway, myo-inositol phosphate synthase (MIPS) and inositol monophosphatase 1 (IMPA1), are identified in tilapia (Oreochromis mossambicus) gill epithelium. Targeted, quantitative, label-free proteomics reveals that they are both upregulated during salinity stress. Upregulation is stronger when fish are exposed to severe (34 ppt acute and 90 ppt gradual) relative to moderate (70 ppt gradual) salinity stress. IMPA1 always responds more strongly than MIPS, suggesting that MIPS is more stable during salinity stress. MIPS is N-terminally acetylated and the corresponding peptide increases proportionally to MIPS protein, while non-acetylated N-terminal peptide is not detectable, indicating that MIPS acetylation is constitutive and may serve to stabilize the protein. Hyperosmotic induction of MIPS and IMPA1 is confirmed using western blot and real-time qPCR and is much higher at the mRNA than at the protein level. Two distinct MIPS mRNA variants are expressed in the gill, but one is more strongly regulated by salinity than the other. A single MIPS gene is encoded in the tilapia genome whereas the zebrafish genome lacks MIPS entirely. The genome of euryhaline tilapia contains four IMPA genes, two of which are expressed, but only one is salinity regulated in gill epithelium. The genome of stenohaline zebrafish contains a single IMPA gene. We conclude that the MIB pathway represents a major salinity stress coping mechanism that is regulated at multiple levels in euryhaline fish but absent in stenohaline zebrafish.

  16. Epithelium-specific deletion of TGF-β receptor type II protects mice from bleomycin-induced pulmonary fibrosis.

    Science.gov (United States)

    Li, Min; Krishnaveni, Manda Sai; Li, Changgong; Zhou, Beiyun; Xing, Yiming; Banfalvi, Agnes; Li, Aimin; Lombardi, Vincent; Akbari, Omid; Borok, Zea; Minoo, Parviz

    2011-01-01

    Idiopathic pulmonary fibrosis (IPF) is a chronic fibroproliferative pulmonary disorder for which there are currently no treatments. Although the etiology of IPF is unknown, dysregulated TGF-β signaling has been implicated in its pathogenesis. Recent studies also suggest a central role for abnormal epithelial repair. In this study, we sought to elucidate the function of epithelial TGF-β signaling via TGF-β receptor II (TβRII) and its contribution to fibrosis by generating mice in which TβRII was specifically inactivated in mouse lung epithelium. These mice, which are referred to herein as TβRIINkx2.1-cre mice, were used to determine the impact of TβRII inactivation on (a) embryonic lung morphogenesis in vivo; and (b) the epithelial cell response to TGF-β signaling in vitro and in a bleomycin-induced, TGF-β-mediated mouse model of pulmonary fibrosis. Although postnatally viable with no discernible abnormalities in lung morphogenesis and epithelial cell differentiation, TβRIINkx2.1-cre mice developed emphysema, suggesting a requirement for epithelial TβRII in alveolar homeostasis. Absence of TβRII increased phosphorylation of Smad2 and decreased, but did not entirely block, phosphorylation of Smad3 in response to endogenous/physiologic TGF-β. However, TβRIINkx2.1-cre mice exhibited increased survival and resistance to bleomycin-induced pulmonary fibrosis. To our knowledge, these findings are the first to demonstrate a specific role for TGF-β signaling in the lung epithelium in the pathogenesis of pulmonary fibrosis.

  17. Dynamics and detection of laser induced microbubbles in the retinal pigment epithelium (RPE)

    Science.gov (United States)

    Fritz, Andreas; Ptaszynski, Lars; Stoehr, Hardo; Brinkmann, Ralf

    2007-07-01

    Selective Retina Treatment (SRT) is a new method to treat eye diseases associated with disorders of the RPE. Selective RPE cell damage is achieved by applying a train of 1.7 μs laser pulses at 527 nm. The treatment of retinal diseases as e.g. diabetic maculopathy (DMP), is currently investigated within clinical studies, however 200 ns pulse durations are under investigation. Transient micro bubbles in the retinal pigment epithelium (RPE) are expected to be the origin of cell damage due to irradiation with laser pulses shorter than 50 μs. The bubbles emerge at the strongly absorbing RPE melanosomes. Cell membrane disruption caused by the transient associated volume increase is expected to be the origin of the angiographically observed RPE leakage. We investigate micro bubble formation and dynamics in porcine RPE using pulse durations of 150 ns. A laser interferometry system at 830 nm with the aim of an online dosimetry control for SRT was developed. Bubble formation was detected interferometrically and by fast flash photography. A correlation to cell damage observed with a vitality stain is found. A bubble detection algorithm is presented.

  18. Regulatory T Cells Promote β-Catenin–Mediated Epithelium-to-Mesenchyme Transition During Radiation-Induced Pulmonary Fibrosis

    Energy Technology Data Exchange (ETDEWEB)

    Xiong, Shanshan; Pan, Xiujie; Xu, Long; Yang, Zhihua [Beijing Institute of Radiation Medicine, Beijing (China); Guo, Renfeng [Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan (United States); Gu, Yongqing; Li, Ruoxi; Wang, Qianjun; Xiao, Fengjun; Du, Li; Zhou, Pingkun [Beijing Institute of Radiation Medicine, Beijing (China); Zhu, Maoxiang, E-mail: zhumx@nic.bmi.ac.cn [Beijing Institute of Radiation Medicine, Beijing (China)

    2015-10-01

    Purpose: Radiation-induced pulmonary fibrosis results from thoracic radiation therapy and severely limits radiation therapy approaches. CD4{sup +}CD25{sup +}FoxP3{sup +} regulatory T cells (Tregs) as well as epithelium-to-mesenchyme transition (EMT) cells are involved in pulmonary fibrosis induced by multiple factors. However, the mechanisms of Tregs and EMT cells in irradiation-induced pulmonary fibrosis remain unclear. In the present study, we investigated the influence of Tregs on EMT in radiation-induced pulmonary fibrosis. Methods and Materials: Mice thoraxes were irradiated (20 Gy), and Tregs were depleted by intraperitoneal injection of a monoclonal anti-CD25 antibody 2 hours after irradiation and every 7 days thereafter. Mice were treated on days 3, 7, and 14 and 1, 3, and 6 months post irradiation. The effectiveness of Treg depletion was assayed via flow cytometry. EMT and β-catenin in lung tissues were detected by immunohistochemistry. Tregs isolated from murine spleens were cultured with mouse lung epithelial (MLE) 12 cells, and short interfering RNA (siRNA) knockdown of β-catenin in MLE 12 cells was used to explore the effects of Tregs on EMT and β-catenin via flow cytometry and Western blotting. Results: Anti-CD25 antibody treatment depleted Tregs efficiently, attenuated the process of radiation-induced pulmonary fibrosis, hindered EMT, and reduced β-catenin accumulation in lung epithelial cells in vivo. The coculture of Tregs with irradiated MLE 12 cells showed that Tregs could promote EMT in MLE 12 cells and that the effect of Tregs on EMT was partially abrogated by β-catenin knockdown in vitro. Conclusions: Tregs can promote EMT in accelerating radiation-induced pulmonary fibrosis. This process is partially mediated through β-catenin. Our study suggests a new mechanism for EMT, promoted by Tregs, that accelerates radiation-induced pulmonary fibrosis.

  19. Cigarette smoking induced liver insult concomitant with inflammatory mediators in serum crevicular fluid and bronchio alveolar lavage of schistosomal diabetic subjects with history of bronchial asthma.

    Science.gov (United States)

    El-Dardiry, Samia A; Shafik, Sherine R; Wagih, Ayman; Amir, El-Amir M; Kassem, Gamal K; Atef, Ghada; El-Toukhy, Heba

    2007-08-01

    Forty five smokers were classified into schistosomal cases with type-2 diabetis mellitus (GI) and with associated history of bronchial asthma (GII) and without T-2 DM (GIII). A control group (GIV) of non-diabetic non schistosomal age matched subjects who quitted smoking for >6 months were included. Assessed parameters included indices of glycemic status (glycated hemoglobin), angiogenesis (vascular endothelial growth factor) hepatic and bronchoalveolar disposition (Liver function test, metallothionein, serum levels of cotinine, cadmium selenium, copper & zinc) and bronchoalveolar lavage) (BAL) levels of surfactant proteins A & D, zinc and copper oxidative stress and fibrogenesis (total antioxidant capacity thiobarbituric acid reactive substance) and vasculopathy (angiotensin converting enzyme, P-selectin, nitrate) and periodontitis (collagenase and elastase in GCF) impact of cigarette smoking associated with trace element disbalance and enzymatic changes in crevicular fluid on altered parameters collaborative out-come. The study reflected the collaborative outcome of immune mediated mechanisms initiated by liver affection, glycemic status and history of predisposed bronchial integrity induced by oxidative stress.

  20. Light-induced damage and its diagnosis in two-photon excited autofluorescence imaging of retinal pigment epithelium cells

    Science.gov (United States)

    Chen, Danni; Qu, Junle; Xu, Gaixia; Zhao, Lingling; Niu, Hanben

    2007-05-01

    In this paper, a novel method for the differentiation of the retinal pigment epithelium (RPE) cells after light-induced damage by two-photon excitation is presented. Fresh samples of RPE cells of pig eyes are obtained from local slaughterhouse. Light-induced damage is produced by the output from Ti: sapphire laser which is focused onto the RPE layer. We study the change of the autofluorescence properties of RPE after two-photon excitation with the same wavelength. Preliminary results show that after two-photon excitation, there are two clear changes in the emission spectrum. The first change is the blue-shift of the emission peak. The emission peak of the intact RPE is located at 592nm, and after excitation, it shifts to 540nm. It is supposed that the excitation has led to the increased autofluorescence of flavin whose emission peak is located at 540nm. The second change is the increased intensity of the emission peak, which might be caused by the accelerated aging because the autofluorescence of RPE would increase during aging process. Experimental results indicate that two-photon excitation could not only lead to the damage of the RPE cells in multiphoton RPE imaging, but also provide an evaluation of the light-induced damage.

  1. Phloroglucinol protects retinal pigment epithelium and photoreceptor against all-trans-retinal-induced toxicity and inhibits A2E formation.

    Science.gov (United States)

    Cia, David; Cubizolle, Aurélie; Crauste, Céline; Jacquemot, Nathalie; Guillou, Laurent; Vigor, Claire; Angebault, Claire; Hamel, Christian P; Vercauteren, Joseph; Brabet, Philippe

    2016-09-01

    Among retinal macular diseases, the juvenile recessive Stargardt disease and the age-related degenerative disease arise from carbonyl and oxidative stresses (COS). Both stresses originate from an accumulation of all-trans-retinal (atRAL) and are involved in bisretinoid formation by condensation of atRAL with phosphatidylethanolamine (carbonyl stress) in the photoreceptor and its transformation into lipofuscin bisretinoids (oxidative stress) in the retinal pigment epithelium (RPE). As atRAL and bisretinoid accumulation contribute to RPE and photoreceptor cell death, our goal is to select powerful chemical inhibitors of COS. Here, we describe that phloroglucinol, a natural phenolic compound having anti-COS properties, protects both rat RPE and mouse photoreceptor primary cultures from atRAL-induced cell death and reduces hydrogen peroxide (H2 O2 )-induced damage in RPE in a dose-dependent manner. Mechanistic analyses demonstrate that the protective effect encompasses decrease in atRAL-induced intracellular reactive oxygen species and free atRAL levels. Moreover, we show that phloroglucinol reacts with atRAL to form a chromene adduct which prevents bisretinoid A2E synthesis in vitro. Taken together, these data show that the protective effect of phloroglucinol correlates with its ability to trap atRAL and to prevent its further transformation into deleterious bisretinoids. Phloroglucinol might be a good basis to develop efficient therapeutic derivatives in the treatment of retinal macular diseases.

  2. Persistence of smoking-induced dysregulation of miRNA expression in the small airway epithelium despite smoking cessation.

    Directory of Open Access Journals (Sweden)

    Guoqing Wang

    Full Text Available Even after quitting smoking, the risk of the development of chronic obstructive pulmonary disease (COPD and lung cancer remains significantly higher compared to healthy nonsmokers. Based on the knowledge that COPD and most lung cancers start in the small airway epithelium (SAE, we hypothesized that smoking modulates miRNA expression in the SAE linked to the pathogenesis of smoking-induced airway disease, and that some of these changes persist after smoking cessation. SAE was collected from 10th to 12th order bronchi using fiberoptic bronchoscopy. Affymetrix miRNA 2.0 arrays were used to assess miRNA expression in the SAE from 9 healthy nonsmokers and 10 healthy smokers, before and after they quit smoking for 3 months. Smoking status was determined by urine nicotine and cotinine measurement. There were significant differences in the expression of 34 miRNAs between healthy smokers and healthy nonsmokers (p1.5, with functions associated with lung development, airway epithelium differentiation, inflammation and cancer. After quitting smoking for 3 months, 12 out of the 34 miRNAs did not return to normal levels, with Wnt/β-catenin signaling pathway being the top identified enriched pathway of the target genes of the persistent dysregulated miRNAs. In the context that many of these persistent smoking-dependent miRNAs are associated with differentiation, inflammatory diseases or lung cancer, it is likely that persistent smoking-related changes in SAE miRNAs play a role in the subsequent development of these disorders.

  3. Changes in liquid clearance of alveolar epithelium after oleic acid-induced acute lung injury in rats

    Institute of Scientific and Technical Information of China (English)

    陶军; 杨天德; 陈祥瑞; 黄河

    2004-01-01

    Objective:Impaired active fluid transport of alveolar epithelium may involve in the pathogenesis and resolution of alveolar edema. Thc objective of this study was to explore the changes in alveolar epithelial liquid clearance during lung edema following acute lung injury induced by oleic acid. Methods:Forty-eight Wistar rats were randomly divided into six groups, I.e. , injured, amiloride, ouabain, amiloride plus ouabain and terbutaline groups. Twenty- four hours after the induction of acute lung injury by intravenous oleic acid (0.25 ml/kg), 5% albumin solution with 1.5 μCi 125Ⅰ-labeled albumin (5 ml/kg) was delivered into both lungs via trachea. Alveolar liquid clearance (ALC), extravascular lung water ( EVLW ) content and arterial blood gases were measured one hour thereafter.Results: At 24 h after the infusion of oleic acid, the rats developed pulmonary edema and severe hypoxemia, with EVLW increased by 47.9% and ALC decreased by 49.2%. Addition of either 2 × 10-3 M amiloride or 5 × 10-4 M ouabain to the instillation further reduced ALC and increased EVLW. ALC increased by approximately 63.7% and EVLW decreased by 46.9% with improved hypoxemia in the Terbutaline (10-4 M) group, compared those in injured rats. A significant negative correlation was found between the increment of EVLW and the reduction of ALC. Onclusions:Active fluid transport of alveolar epithelium might play a role in the pathogenesis of lung edema in acute lung injury.

  4. Bilateral Entry and Release of Middle East Respiratory Syndrome Coronavirus Induces Profound Apoptosis of Human Bronchial Epithelial Cells

    Science.gov (United States)

    Tao, Xinrong; Hill, Terence E.; Morimoto, Chikao; Peters, Clarence J.; Ksiazek, Thomas G.

    2013-01-01

    The newly emerged Middle East respiratory syndrome coronavirus (MERS-CoV) infects human bronchial epithelial Calu-3 cells. Unlike severe acute respiratory syndrome (SARS)-CoV, which exclusively infects and releases through the apical route, this virus can do so through either side of polarized Calu-3 cells. Infection results in profound apoptosis within 24 h irrespective of its production of titers that are lower than those of SARS-CoV. Together, our results provide new insights into the dissemination and pathogenesis of MERS-CoV and may indicate that the virus differs markedly from SARS-CoV. PMID:23824802

  5. Enhanced levels of glutathione and protein glutathiolation in rat tongue epithelium during 4-NQO-induced carcinogenesis.

    Science.gov (United States)

    Huang, Zhishan; Komninou, Despina; Kleinman, Wayne; Pinto, John T; Gilhooly, Elaine M; Calcagnotto, Ana; Richie, John P

    2007-04-01

    High glutathione (GSH) levels are commonly found in oral tumors and are thought to play an important role in tumorigenesis. While posttranslational binding of GSH to cellular proteins (protein glutathiolation) has recently been recognized as an important redox-sensitive regulatory mechanism, no data currently exist on this process during carcinogenesis. Our goal was to determine the effects of 4-nitroquinoline-N-oxide (4-NQO)-induced carcinogenesis on tongue levels of protein-bound and free GSH and related thiols in the rat. Male F-344 rats (6 weeks of age) were administered either 4-NQO (20 ppm) in drinking water or tap water alone (controls) for 8 weeks. Twenty-four weeks after cessation of 4-NQO, squamous cell carcinomas of the tongue were observed in all rats. The levels of both free and bound GSH in tumors, as well as in adjacent tissues, were 2- to 3-fold greater than in tongue epithelium from control rats (p tongue tissues from control rats (ptongue tissues from 4-NQO treated vs. control rats (p<0.05). Altogether, these results suggest that protein glutathiolation, together with GSH and GSSG levels, are induced during oral carcinogenesis in the rat possibly as a result of enhanced levels of oxidative stress.

  6. Antigen-induced bronchial anaphylaxis in actively sensitized guinea-pigs: effect of long-term treatment with sodium cromoglycate and aminophylline.

    Science.gov (United States)

    Andersson, P.; Bergstrand, H.

    1981-01-01

    1 The effects of long-term treatment with sodium cromoglycate (SCG) and aminophylline on antigen-induced bronchoconstriction have been studied in guinea-pigs actively sensitized according to two different regimens (one producing IgE- and IgG-like antibodies and the other producing exclusively IgG-like antibodies). 2 Treatment for three weeks with SCG (10 mg/kg) and aminophylline (10, 30 or 60 mg/kg) led to a decreased bronchial response capacity which persisted even three days after treatment ceased. In this respect SCG was effective only in guinea-pigs sensitized to produce at least partly IgE-like antibodies; aminophylline was effective in guinea-pigs sensitized to produce both IgE and/or IgG antibodies. 3 The results in vivo with SCG were reflected in vitro by a reduced capacity of chopped lung tissue to release histamine at antigen challenge; lungs from animals treated with aminophylline did not show reduced histamine releasing capacity. 4 Acute treatment with atropine was shown to reduce significantly the antigen-induced bronchial contraction in guinea-pigs sensitized to produce both IgE- and IgG-antibodies. No effect of atropine was seen on an IgG-mediated anaphylaxis. 5 Increased reactivity to methacholine but not to histamine was seen in guinea-pigs sensitized to produce both IgG- and IgE-antibodies. Long-term treatment with SCG did not affect this hyperreactivity to methacholine. 6 Decreased reactivity to isoprenaline was found in isolated tracheae taken from guinea-pigs sensitized to produce both IgE- and IgG-like antibodies compared to unsensitized guinea-pigs. Long-term treatment with SCG, but not with aminophylline, reversed this decreased reactivity. PMID:6170376

  7. Constitutive expression of inducible nitric oxide synthase in the normal human colonic epithelium

    DEFF Research Database (Denmark)

    Perner, A; Andresen, Lars; Normark, M;

    2002-01-01

    Inducible nitric oxide synthase (iNOS) in the human colon is considered expressed only in inflammatory states such as ulcerative or collagenous colitis. As subtle iNOS labelling was previously observed in some colonic mucosal biopsies from a heterogeneous group of controls with non-inflamed bowel...

  8. The low PLC-δ1 expression in cystic fibrosis bronchial epithelial cells induces upregulation of TRPV6 channel activity.

    Science.gov (United States)

    Vachel, Laura; Norez, Caroline; Jayle, Christophe; Becq, Frédéric; Vandebrouck, Clarisse

    2015-01-01

    Increase of Ca(2+) influx in Cystic Fibrosis (CF) cells has been reported to be related to Transient Receptor Potential Canonical (TRPC6) channel, which is implicated in a functional coupling with Cystic Fibrosis Transmembrane conductance Regulator (CFTR). Several members of the Transient Receptor Potential Vanilloid (TRPV) channels family have already been described as emerging target for respiratory diseases. Two specific isoforms, TRPV5 and TRPV6 are of particular interest in the context of CF Ca(2+) homeostasis as they are highly selective toward Ca(2+) and constitutively activated. Thus, we investigated the involvement of these channels in Ca(2+) influx in CF and non-CF human bronchial epithelial cell lines. 16HBE14o-, CFBE41o- cell lines, primary human airway epithelial cells (hAEC) and freshly isolated human airway epithelial cells from CF and non-CF individuals were used. We showed that both channels are expressed in CF and non-CF cells and constitutive Ca(2+) influx was significantly higher (85%) in cells from CF individuals compared to cells from non-CF ones. Using the selective inhibitor of TRPV6 channel SOR-C27 and a siRNA strategy, our results revealed that TRPV6 was mostly involved in the increase of Ca(2+) influx. TRPV6 channel is negatively regulated by the PLC-PIP2 pathway. We measured the Ca(2+) influx in the presence of the non-specific PLC inhibitor, U73122, in non-CF human bronchial epithelial cells. Ca(2+) influx was increased by 33% with U73122 and this increase was largely reduced in the presence of SOR-C27. PLC inhibition in CF cells by U73122 had no effect on Ca(2+) influx. These results showed that PLC-PIP2 pathway is dysregulated in CF cells and leads to the increase of TRPV6 activity. The regulation of TRPV6 by PLC-PIP2 pathway implicates the specific PLC isoform, PLC-δ1. Immunoblot experiments revealed that expression of PLC-δ1 was decreased by 70% in CF cells. TRPV6 activity was normalized but not the level of expression of PLC-δ1

  9. Mechanical compression attenuates normal human bronchial epithelial wound healing

    Directory of Open Access Journals (Sweden)

    Malavia Nikita

    2009-02-01

    Full Text Available Abstract Background Airway narrowing associated with chronic asthma results in the transmission of injurious compressive forces to the bronchial epithelium and promotes the release of pro-inflammatory mediators and the denudation of the bronchial epithelium. While the individual effects of compression or denudation are well characterized, there is no data to elucidate how these cells respond to the application of mechanical compression in the presence of a compromised epithelial layer. Methods Accordingly, differentiated normal human bronchial epithelial cells were exposed to one of four conditions: 1 unperturbed control cells, 2 single scrape wound only, 3 static compression (6 hours of 30 cmH2O, and 4 6 hours of static compression after a scrape wound. Following treatment, wound closure rate was recorded, media was assayed for mediator content and the cytoskeletal network was fluorescently labeled. Results We found that mechanical compression and scrape injury increase TGF-β2 and endothelin-1 secretion, while EGF content in the media is attenuated with both injury modes. The application of compression after a pre-existing scrape wound augmented these observations, and also decreased PGE2 media content. Compression stimulated depolymerization of the actin cytoskeleton and significantly attenuated wound healing. Closure rate was partially restored with the addition of exogenous PGE2, but not EGF. Conclusion Our results suggest that mechanical compression reduces the capacity of the bronchial epithelium to close wounds, and is, in part, mediated by PGE2 and a compromised cytoskeleton.

  10. Generation of corneal epithelial cells from induced pluripotent stem cells derived from human dermal fibroblast and corneal limbal epithelium.

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    Ryuhei Hayashi

    Full Text Available Induced pluripotent stem (iPS cells can be established from somatic cells. However, there is currently no established strategy to generate corneal epithelial cells from iPS cells. In this study, we investigated whether corneal epithelial cells could be differentiated from iPS cells. We tested 2 distinct sources: human adult dermal fibroblast (HDF-derived iPS cells (253G1 and human adult corneal limbal epithelial cells (HLEC-derived iPS cells (L1B41. We first established iPS cells from HLEC by introducing the Yamanaka 4 factors. Corneal epithelial cells were successfully induced from the iPS cells by the stromal cell-derived inducing activity (SDIA differentiation method, as Pax6(+/K12(+ corneal epithelial colonies were observed after prolonged differentiation culture (12 weeks or later in both the L1B41 and 253G1 iPS cells following retinal pigment epithelial and lens cell induction. Interestingly, the corneal epithelial differentiation efficiency was higher in L1B41 than in 253G1. DNA methylation analysis revealed that a small proportion of differentially methylated regions still existed between L1B41 and 253G1 iPS cells even though no significant difference in methylation status was detected in the specific corneal epithelium-related genes such as K12, K3, and Pax6. The present study is the first to demonstrate a strategy for corneal epithelial cell differentiation from human iPS cells, and further suggests that the epigenomic status is associated with the propensity of iPS cells to differentiate into corneal epithelial cells.

  11. Evidence for an adenoma-carcinoma sequence in dimethylhydrazine-induced neoplasms of rat intestinal epithelium.

    OpenAIRE

    1983-01-01

    Carcinogen-induced primary intestinal adenocarcinomas serve as a useful animal model for human colonic adenocarcinomas. Although striking similarities between this model and the human disease state exist, there are also troublesome discrepancies-a major one being the reported lack of an adenoma-carcinoma sequence in the experimental model. However, the original morphologic descriptions of these experimental neoplasms predated the development of presently accepted morphologic criteria that hav...

  12. Deriving retinal pigment epithelium (RPE) from induced pluripotent stem (iPS) cells by different sizes of embryoid bodies.

    Science.gov (United States)

    Muñiz, Alberto; Ramesh, Kaini R; Greene, Whitney A; Choi, Jae-Hyek; Wang, Heuy-Ching

    2015-02-04

    Pluripotent stem cells possess the ability to proliferate indefinitely and to differentiate into almost any cell type. Additionally, the development of techniques to reprogram somatic cells into induced pluripotent stem (iPS) cells has generated interest and excitement towards the possibility of customized personal regenerative medicine. However, the efficiency of stem cell differentiation towards a desired lineage remains low. The purpose of this study is to describe a protocol to derive retinal pigment epithelium (RPE) from iPS cells (iPS-RPE) by applying a tissue engineering approach to generate homogenous populations of embryoid bodies (EBs), a common intermediate during in vitro differentiation. The protocol applies the formation of specific size of EBs using microwell plate technology. The methods for identifying protein and gene markers of RPE by immunocytochemistry and reverse-transcription polymerase chain reaction (RT-PCR) are also explained. Finally, the efficiency of differentiation in different sizes of EBs monitored by fluorescence-activated cell sorting (FACS) analysis of RPE markers is described. These techniques will facilitate the differentiation of iPS cells into RPE for future applications.

  13. HAIR CELL-LIKE CELL GENERATION INDUCED BY NATURE CULTURE OF ADULT RAT AUDITORY EPITHELIUM

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Hair cells are the mechanosensory cells thatconvert sound and motion signals into electrical i m-pulses in cochlear and vestibular end organs of innerear.Although mature mammals nor mally do notgenerate new hair cells,recentin vivoandin vitrostudies have demonstrated mitotic activity and i m-mature-looking hair cells in mammalian vestibularepithelia after exposure to ototoxic drugs[1-3],sug-gesting that vestibular hair cell regeneration inmammals may be inducible.However,the possibil-ity of auditory hair ce...

  14. The role of alveolar epithelium in radiation-induced lung injury.

    Directory of Open Access Journals (Sweden)

    Celine Almeida

    Full Text Available Pneumonitis and fibrosis are major lung complications of irradiating thoracic malignancies. In the current study, we determined the effect of thoracic irradiation on the lungs of FVB/N mice. Survival data showed a dose-dependent increase in morbidity following thoracic irradiation with single (11-13 Gy and fractionated doses (24-36 Gy of (137Cs γ-rays. Histological examination showed a thickening of vessel walls, accumulation of inflammatory cells, collagen deposition, and regional fibrosis in the lungs 14 weeks after a single 12 Gy dose and a fractionated 30 Gy dose; this damage was also seen 5 months after a fractionated 24 Gy dose. After both single and fractionated doses, i] aquaporin-5 was markedly decreased, ii] E-cadherin was reduced and iii] prosurfactant Protein C (pro-SP-c, the number of pro-SP-c(+ cells and vimentin expression were increased in the lungs. Immunofluorescence analysis revealed co-localization of pro-SP-c and α-smooth muscle actin in the alveoli after a single dose of 12 Gy. These data suggest that, i] the FVB/N mouse strain is sensitive to thoracic radiation ii] aquaporin-5, E-cadherin, and pro-SP-c may serve as sensitive indicators of radiation-induced lung injury; and iii] the epithelial-to-mesenchymal transition may play an important role in the development of radiation-induced lung fibrosis.

  15. Campylobacter jejuni induces transcytosis of commensal bacteria across the intestinal epithelium through M-like cells

    Directory of Open Access Journals (Sweden)

    Kalischuk Lisa D

    2010-11-01

    Full Text Available Abstract Background Recent epidemiological analyses have implicated acute Campylobacter enteritis as a factor that may incite or exacerbate inflammatory bowel disease (IBD in susceptible individuals. We have demonstrated previously that C. jejuni disrupts the intestinal barrier function by rapidly inducing epithelial translocation of non-invasive commensal bacteria via a transcellular lipid raft-mediated mechanism ('transcytosis'. To further characterize this mechanism, the aim of this current study was to elucidate whether C. jejuni utilizes M cells to facilitate transcytosis of commensal intestinal bacteria. Results C. jejuni induced translocation of non-invasive E. coli across confluent Caco-2 epithelial monolayers in the absence of disrupted transepithelial electrical resistance or increased permeability to a 3 kDa dextran probe. C. jejuni-infected monolayers displayed increased numbers of cells expressing the M cell-specific marker, galectin-9, reduced numbers of enterocytes that stained with the absorptive enterocyte marker, Ulex europaeus agglutinin-1, and reduced activities of enzymes typically associated with absorptive enterocytes (namely alkaline phosphatase, lactase, and sucrase. Furthermore, in Campylobacter-infected monolayers, E. coli were observed to be internalized specifically within epithelial cells displaying M-like cell characteristics. Conclusion These data indicate that C. jejuni may utilize M cells to promote transcytosis of non-invasive bacteria across the intact intestinal epithelial barrier. This mechanism may contribute to the inflammatory immune responses against commensal intestinal bacteria commonly observed in IBD patients.

  16. The role of alveolar epithelium in radiation-induced lung injury.

    Science.gov (United States)

    Almeida, Celine; Nagarajan, Devipriya; Tian, Jian; Leal, Sofia Walder; Wheeler, Kenneth; Munley, Michael; Blackstock, William; Zhao, Weiling

    2013-01-01

    Pneumonitis and fibrosis are major lung complications of irradiating thoracic malignancies. In the current study, we determined the effect of thoracic irradiation on the lungs of FVB/N mice. Survival data showed a dose-dependent increase in morbidity following thoracic irradiation with single (11-13 Gy) and fractionated doses (24-36 Gy) of (137)Cs γ-rays. Histological examination showed a thickening of vessel walls, accumulation of inflammatory cells, collagen deposition, and regional fibrosis in the lungs 14 weeks after a single 12 Gy dose and a fractionated 30 Gy dose; this damage was also seen 5 months after a fractionated 24 Gy dose. After both single and fractionated doses, i] aquaporin-5 was markedly decreased, ii] E-cadherin was reduced and iii] prosurfactant Protein C (pro-SP-c), the number of pro-SP-c(+) cells and vimentin expression were increased in the lungs. Immunofluorescence analysis revealed co-localization of pro-SP-c and α-smooth muscle actin in the alveoli after a single dose of 12 Gy. These data suggest that, i] the FVB/N mouse strain is sensitive to thoracic radiation ii] aquaporin-5, E-cadherin, and pro-SP-c may serve as sensitive indicators of radiation-induced lung injury; and iii] the epithelial-to-mesenchymal transition may play an important role in the development of radiation-induced lung fibrosis.

  17. Nanoscale Particulate Matter from Urban Traffic Rapidly Induces Oxidative Stress and Inflammation in Olfactory Epithelium with Concomitant Effects on Brain

    Science.gov (United States)

    Cheng, Hank; Saffari, Arian; Sioutas, Constantinos; Forman, Henry J.; Morgan, Todd E.; Finch, Caleb E.

    2016-01-01

    Background: Rodent models for urban air pollution show consistent induction of inflammatory responses in major brain regions. However, the initial impact of air pollution particulate material on olfactory gateways has not been reported. Objective: We evaluated the olfactory neuroepithelium (OE) and brain regional responses to a nanosized subfraction of urban traffic ultrafine particulate matter (nPM, < 200 nm) in vivo, ex vivo, and in vitro. Methods: Adult mice were exposed to reaerosolized nPM for 5, 20, and 45 cumulative hours over 3 weeks. The OE, the olfactory bulb (OB), the cerebral cortex, and the cerebellum were analyzed for oxidative stress and inflammatory responses. Acute responses of the OE to liquid nPM suspensions were studied with ex vivo and primary OE cultures. Results: After exposure to nPM, the OE and OB had rapid increases of 4-hydroxy-2-nonenal (4-HNE) and 3-nitrotyrosine (3-NT) protein adducts, whereas the cerebral cortex and cerebellum did not respond at any time. All brain regions showed increased levels of tumor necrosis factor-α (TNFα) protein by 45 hr, with earlier induction of TNFα mRNA in OE and OB. These responses corresponded to in vitro OE and mixed glial responses, with rapid induction of nitrite and inducible nitric oxide synthase (iNOS), followed by induction of TNFα. Conclusions: These findings show the differential time course of oxidative stress and inflammatory responses to nPM between the OE and the brain. Slow cumulative transport of inhaled nPM into the brain may contribute to delayed responses of proximal and distal brain regions, with potential input from systemic factors. Citation: Cheng H, Saffari A, Sioutas C, Forman HJ, Morgan TE, Finch CE. 2016. Nanoscale particulate matter from urban traffic rapidly induces oxidative stress and inflammation in olfactory epithelium with concomitant effects on brain. Environ Health Perspect 124:1537–1546; http://dx.doi.org/10.1289/EHP134 PMID:27187980

  18. Loss of STAT1 from Mouse Mammary Epithelium Results in an Increased Neu-Induced Tumor Burden

    Directory of Open Access Journals (Sweden)

    Peter J. Klover

    2010-11-01

    Full Text Available Type I and type II classes of interferons (IFNs signal through the JAK/STAT1 pathway and are known to be important in adaptive and innate immune responses and in protection against tumors. Although STAT1 is widely considered a tumor suppressor, it remains unclear, however, if this function occurs in tumor cells (cell autonomous or if STAT1 acts primarily through immune cells. Here, the question of whether STAT1 has a cell autonomous role in mammary tumor formation was addressed in a mouse model of ERBB2/neu-induced breast cancer in the absence and presence of STAT1. For this purpose, mice that carry floxed Stat1 alleles, which permit cell-specific removal of STAT1, were generated. To induce tumors only in mammary cells lacking STAT1, Stat1 floxed mice were crossed with transgenic mice that express cre recombinase and the neu oncogene under the mouse mammary tumor virus LTR (Stat1fl/fl NIC. Stat1 was effectively deleted in mammary epithelium of virgin Stat1fl/fl NIC females. Time-to-tumor onset was significantly shorter in Stat1fl/fl NIC females than in WT NIC (Wilcoxon rank sum test, P = .02. The median time-to-tumor onset in the Stat1fl/fl NIC mice was 49.4 weeks, whereas it was 62.4 weeks in the WT NIC mice. These results suggest that STAT1 in mammary epithelial cells may play a role in suppressing tumorigenesis. The Stat1 floxed allele described in this study is also a unique resource to determine the cellular targets of IFNs and STAT1 action, which should aid our understanding and appreciation of these pathways.

  19. [Metastatic bronchial carcinoid tumors].

    Science.gov (United States)

    Bouledrak, K; Walter, T; Souquet, P J; Lombard-Bohas, C

    2016-02-01

    Bronchial carcinoids are uncommon pulmonary neoplasms and represent 1 to 2 % of all lung tumors. In early stage of disease, the mainstay and only curative treatment is surgery. Bronchial carcinoids are generally regarded as low-grade carcinomas and metastatic dissemination is unusual. The management of the metastatic stage is not currently standardized due to a lack of relevant studies. As bronchial carcinoids and in particular their metastatic forms are rare, we apply treatment strategies that have been evaluated in gastrointestinal and pancreatic neuroendocrine tumors. However, bronchial carcinoids have their own characteristic. A specific therapeutic feature of these metastatic tumors is that they require a dual approach: both anti-secretory for the carcinoid syndrome, and anti-tumoral.

  20. Patterning of wound-induced intercellular Ca2+ flashes in a developing epithelium

    Science.gov (United States)

    Narciso, Cody; Wu, Qinfeng; Brodskiy, Pavel; Garston, George; Baker, Ruth; Fletcher, Alexander; Zartman, Jeremiah

    2015-10-01

    Differential mechanical force distributions are increasingly recognized to provide important feedback into the control of an organ’s final size and shape. As a second messenger that integrates and relays mechanical information to the cell, calcium ions (Ca2+) are a prime candidate for providing important information on both the overall mechanical state of the tissue and resulting behavior at the individual-cell level during development. Still, how the spatiotemporal properties of Ca2+ transients reflect the underlying mechanical characteristics of tissues is still poorly understood. Here we use an established model system of an epithelial tissue, the Drosophila wing imaginal disc, to investigate how tissue properties impact the propagation of Ca2+ transients induced by laser ablation. The resulting intercellular Ca2+ flash is found to be mediated by inositol 1,4,5-trisphosphate and depends on gap junction communication. Further, we find that intercellular Ca2+ transients show spatially non-uniform characteristics across the proximal-distal axis of the larval wing imaginal disc, which exhibit a gradient in cell size and anisotropy. A computational model of Ca2+ transients is employed to identify the principle factors explaining the spatiotemporal patterning dynamics of intercellular Ca2+ flashes. The relative Ca2+ flash anisotropy is principally explained by local cell shape anisotropy. Further, Ca2+ velocities are relatively uniform throughout the wing disc, irrespective of cell size or anisotropy. This can be explained by the opposing effects of cell diameter and cell elongation on intercellular Ca2+ propagation. Thus, intercellular Ca2+ transients follow lines of mechanical tension at velocities that are largely independent of tissue heterogeneity and reflect the mechanical state of the underlying tissue.

  1. Use of salbutamol in detection of mechanism destructive to bronchial patency in dust-induced lung disease

    Energy Technology Data Exchange (ETDEWEB)

    Zhumabekova, B.K.

    1982-04-01

    Different mechanisms destroy the open passibility of the bronchi: bronchospasm, destruction of drop eliminator function of the bronchi, valvular mechanics, change in elastic properties of lungs, dyskinesia of the tracheobronchial tree and inflammatory edema of the mucous envelope. Bronchospasm is the most studied form of bronchial pathology. To detect the bronchospastic component, various bronchodilating means are used: (1) stimulators of adrenergic receptors, (2) blockers of acetylcholine (atropine, bella donna); preparations acting directly on smooth musculature of the bronchi (theophylline, euphylline). The pharmaceutical industry is now making aerosol bronchodilators. Since salbutamol is widely used as an aerosol and opinions of its effectiveness are not uniform, a test was made of it on 35 patients; 22 with chronic bronchitis and 13 with silicosis. The rate of air flow during inspiration and expiration was examined 10, 20, 30 and 40 minutes after administration of salbutamol aerosol. Results of the test are presented in a table and show that the use of a pharmacological test with salbutamol aerosol to detect bronchospasm as a cause of lung obstruction is valid. If 10 minutes after inhalation of salbutamol, a therapeutic effect is observed and inhalation and exhalation increase, bronchospasm as the cause of the pathology is demonstrated. The absence of a measurable reaction to salbutamol after 10 minutes indicates that other mechanisms are the basis of the obstruction. (11 refs.) (In Russian)

  2. Macrophages facilitate coal tar pitch extract-induced tumorigenic transformation of human bronchial epithelial cells mediated by NF-κB.

    Directory of Open Access Journals (Sweden)

    Feifei Feng

    Full Text Available OBJECTIVE: Chronic respiratory inflammation has been associated with lung cancer. Tumor-associated macrophages (TAMs play a critical role in the formation of inflammation microenvironment. We sought to characterize the role of TAMs in coal tar pitch extract (CTPE-induced tumorigenic transformation of human bronchial epithelial cells and the underlying mechanisms. METHODS: The expression of TAMs-specific CD68 in lung cancer tissues and paired adjacent tissues from cancer patients was determined using immunostaining. Co-culture of human bronchial epithelial cells (BEAS-2B and macrophage-like THP-1 cells were conducted to evaluate the promotive effect of macrophages on CTPE-induced tumorigenic transformation of BEAS-2B cells. BEAS-2B cells were first treated with 2.4 µg/mL CTPE for 72 hours. After removal of CTPE, the cells were continuously cultured either with or without THP-1 cells and passaged using trypsin-EDTA. Alterations of cell cycle, karyotype, colony formation in soft agar and tumor xenograft growth in nude mice of BEAS-2B cells at passages 10, 20 and 30, indicative of tumorigenecity, were determined, respectively. In addition, mRNA and protein levels of NF-κB in BEAS-2B cells were measured with RT-PCR and western blot, respectively. B(aP was used as the positive control. RESULTS: The over-expression of TAMs-specific CD68 around lung tumor tissues was detected and associated with lung cancer progression. The tumorigenic alterations of BEAS-2B cells including increase in cell growth rate, number of cells with aneuploidy, clonogenicity in soft agar, and tumor size in nude mice in vivo occurred at passage 10, becoming significant at passages 20 and 30 of the co-culture following CTPE removal in compared to BEAS-2B cells alone. In addition, the expression levels of NF-κB in BEAS-2B cells were positively correlated to the malignancy of BEAS-2B cells under different conditions of treatment. CONCLUSION: The presence of macrophages

  3. Topical Cathelicidin (LL-37) an Innate Immune Peptide Induces Acute Olfactory Epithelium Inflammation in a Mouse Model

    Science.gov (United States)

    Alt, Jeremiah A.; Qin, Xuan; Pulsipher, Abigail; Orb, Quinn; Orlandi, Richard R.; Zhang, Jianxing; Schults, Austin; Jia, Wanjian; Presson, Angela P.; Prestwich, Glenn; Oottamasathien, Siam

    2017-01-01

    Background Cathelicidin (LL-37) is an endogenous innate immune peptide that is elevated in patients with chronic rhinosinusitis (CRS). The role of LL-37 in olfactory epithelium (OE) inflammation remains unknown. We hypothesized that 1) LL-37 topically delivered would elicit profound OE inflammation, and 2) LL-37 induced inflammation is associated with increased infiltration of neutrophils and mast cells. Methods To test our hypothesis we challenged C57BL/6 mice intranasally with increasing concentrations of LL-37. At 24 hours tissues were examined histologically and scored for inflammatory cell infiltrate, edema, and secretory hyperplasia. In separate experiments, fluorescently conjugated LL-37 was instilled and tissues were examined at 0.5 and 24 hours. To test our last hypothesis, we performed tissue myeloperoxidase (MPO) assays for neutrophil activity and immunohistochemistry for tryptase to determine the mean number of mast cells per mm2. Results LL-37 caused increased inflammatory cell infiltrate, edema, and secretory cell hyperplasia of the sinonasal mucosa with higher LL-37 concentrations yielding significantly more inflammatory changes (p < 0.01). Fluorescent LL-37 demonstrated global sinonasal epithelial binding and tissue distribution. Further, higher concentrations of LL-37 led to significantly greater MPO levels with dose-dependent increases in mast cell infiltration (p < 0.01). Conclusions LL-37 has dramatic inflammatory effects in the OE mucosa that is dose-dependent. The observed inflammatory changes in the olfactory mucosa were associated with the infiltration of both neutrophils and mast cells. Our biologic model represents a new model to further investigate the role of LL-37 in OE inflammation. PMID:26346056

  4. Ozone induces a proinflammatory response in primary human bronchial epithelial cells through mitogen-activated protein kinase activation without nuclear factor-κB activation.

    Science.gov (United States)

    McCullough, Shaun D; Duncan, Kelly E; Swanton, Samantha M; Dailey, Lisa A; Diaz-Sanchez, David; Devlin, Robert B

    2014-09-01

    Ground-level ozone (O3) is a ubiquitous environmental air pollutant that is a potent inducer of airway inflammation and has been linked with respiratory and cardiovascular morbidity and mortality. Some studies using transformed or immortalized cells have attributed O3-mediated expression of inflammatory cytokines with activation of the canonical NF-κB pathway. In this study, we sought to characterize the O3-mediated activation of cellular signaling pathways using primary human bronchial epithelial cells obtained from a panel of donors. We demonstrate that the O3-induced expression of proinflammatory cytokines requires the activation of the epidermal growth factor receptor/MEK/ERK and MKK4/p38 mitogen-activated signaling pathways but does not appear to involve activation of canonical NF-κB signaling. In addition to providing a novel mechanistic model for the O3-mediated induction of proinflammatory cytokines, these findings highlight the importance of using primary cells over cell lines in mechanistic studies.

  5. Experimental Study onMalignant Transformation of Human Bronchial Epithelial CellsInduced by Glycidyl Methacrylate and Analysis on its Methylation

    Institute of Scientific and Technical Information of China (English)

    WANG An Na; WANG Quan Kai; YANG Min; HU Jie; DONG Lin; andXU Jian Ning

    2014-01-01

    ObjectiveTo establish the model of human bronchial epithelial cells(16HBE) malignant transformation induced by glycidyl methacrylate(GMA)and define the different methylation genes at different stages. MethodsDNA was extracted at different 16HBE malignant phasesandchanges of genes DNA methylation atdifferent stages weredetectedusing Methylation chip of‘NimbleGen HG18 CpG Promoter Microarray Methylation’. Methylation-specific PCR (MSP) was usedto observe the methylation status ofsome genes, and then compared with the control groups. ResultsThe resultshowed that GMA induced 16HBE morphorlogical transformation at the dose of 8µg/mL, and cell exposed to GMA had 1374 genes in protophase, 825 genes inmetaphase, 1149 genes in anaphase, respectively; 30 genes are all methylation in the 3 stages; 318 genes in protophase but not inmetaphase and anaphase; 272 genes in metaphase but not inprotophase and anaphase; 683 genes in anaphase but not inmetaphase and protophase; 73 genes inprotophase andmetaphase but not in anaphase; 67 genes in protophase and anaphase but not inmetaphase; 59 genes inmetaphase and anaphase but not in protophase. ConclusionThe pattern of DNA methylation could change in the process of 16HBEinduced by GMA.

  6. DNA damages induced by trans, trans-2,4-decadienal (tt-DDE), a component of cooking oil fume, in human bronchial epithelial cells.

    Science.gov (United States)

    Young, Shun-Chieh; Chang, Louis W; Lee, Hui-Ling; Tsai, Lung-Hung; Liu, Yin-Chang; Lin, Pinpin

    2010-05-01

    Epidemiological studies have demonstrated that cooking oil fumes (COF) are an environmental risk factor for the development of lung adenocarcinoma among nonsmoking females in Taiwan. Aside from polycyclic aromatic hydrocarbons, aldehydes, especially trans, trans-2,4-decadienal (tt-DDE) are found to be abundant in COF. Although there is indication that tt-DDE induces DNA damage, the precise role of tt-DDE in the induction of DNA damage in lung cells is still not clear. When we assessed DNA breaks with the Comet assay, we found that the DNA breaks induced by 1 muM tt-DDE in human bronchial epithelial cells (BEAS-2B) could be significantly reduced by antioxidants, suggesting that oxidative stress was involved. Indeed, when tt-DDE-treated cells were coincubated with endonuclease III/formamidopyrimidine-DNA glycosylase or with nuclear extract (NE), an enhancement of DNA breaks was observed at 1 hr after tt-DDE exposure. Furthermore, when NE was incubated with an antibody against 8-oxoguanine DNA glycosylase (anti-OGG1), a reduction in tt-DDE/NE-induced DNA breaks could be demonstrated. Since OGG1 is a specific repair enzyme for 8-oxo-deoxyguanosine (8-oxo-dG), these findings indicated that 8-oxo-dG was involved. On the other hand, when NE was incubated with antibodies against nucleotide excision repair enzymes, there was a significant reduction in tt-DDE/NE-induced DNA breaks at 4 hr after tt-DDE treatment. These observations indicate that, in addition to early oxidative DNA damage, nonoxidative DNA damage such as bulky adduct formation, was also induced by tt-DDE. Our study further affirms that tt-DDE is genotoxic to human lung cells and can increase carcinogenic risk.

  7. Cadmium induces cytotoxicity in human bronchial epithelial cells through upregulation of eIF5A1 and NF-kappaB

    Energy Technology Data Exchange (ETDEWEB)

    Chen, De-Ju; Xu, Yan-Ming; Du, Ji-Ying [Laboratory of Cancer Biology and Epigenetics, Shantou University Medical College, Shantou, Guangdong 515041 (China); Department of Cell Biology and Genetics, Shantou University Medical College, Shantou, Guangdong 515041 (China); Huang, Dong-Yang [Department of Cell Biology and Genetics, Shantou University Medical College, Shantou, Guangdong 515041 (China); Lau, Andy T.Y., E-mail: andytylau@stu.edu.cn [Laboratory of Cancer Biology and Epigenetics, Shantou University Medical College, Shantou, Guangdong 515041 (China); Department of Cell Biology and Genetics, Shantou University Medical College, Shantou, Guangdong 515041 (China)

    2014-02-28

    Highlights: • Normal human bronchial epithelial cells (BEAS-2B) were dosed with cadmium (Cd). • A low level (2 μM) of Cd treatment for 36 h elicited negligible cytotoxicity. • High levels (20 or 30 μM) of Cd treatment for 36 h induced cell death. • High levels of Cd can upregulate the protein levels of eIF5A1 and NF-κB p65. • We suggest that eIF5A1 level is possibly modulated by NF-κB. - Abstract: Cadmium (Cd) and Cd compounds are widely-distributed in the environment and well-known carcinogens. Here, we report that in CdCl{sub 2}-exposed human bronchial epithelial cells (BEAS-2B), the level of p53 is dramatically decreased in a time- and dose-dependent manner, suggesting that the observed Cd-induced cytotoxicity is not likely due to the pro-apoptotic function of p53. Therefore, this prompted us to further study the responsive pro-apoptotic factors by proteomic approaches. Interestingly, we identified that high levels (20 or 30 μM) of Cd can significantly upregulate the protein levels of eukaryotic translation initiation factor 5A1 (eIF5A1) and redox-sensitive transcription factor NF-κB p65. Moreover, there is an enhanced NF-κB nuclear translocation as well as chromatin-binding in Cd-treated BEAS-2B cells. We also show that small interfering RNA-specific knockdown of eIF5A1 in Cd-exposed cells attenuated the Cd cytotoxicity, indicating the potential role of eIF5A1 in Cd cytotoxicity. As eIF5A1 is reported to be related with cell apoptosis but little is known about its transcriptional control, we hypothesize that NF-κB might likely modulate eIF5A1 gene expression. Notably, by bioinformatic analysis, several potential NF-κB binding sites on the upstream promoter region of eIF5A1 gene can be found. Subsequent chromatin immunoprecipitation assay revealed that indeed there is enhanced NF-κB binding on eIF5A1 promoter region of Cd-treated BEAS-2B cells. Taken together, our findings suggest for the first time a regulatory mechanism for the pro

  8. TCM Diet Therapy for Bronchial Asthma

    Institute of Scientific and Technical Information of China (English)

    DENG Zi

    2009-01-01

    @@ Bronchial asthma is a disease with reversible tracheospasm and tracheostenosis due to excessively increased tracheal-bronchial reactivity induced by sensitinogen or non-sensitinogen. Although its etiology is complicated, the disease is generally caused by internal injury resulting from accumulation of phlegm in the lungs, damage to the spleen by improper diet and impairment of the kidneys by overstrain and excessive coitus;or it can be caused by six exogenous pathogenic factors, with obstruction of the airways by phlegm and upward adverse flow of the lung-qi.

  9. P190B RhoGAP overexpression in the developing mammary epithelium induces TGFβ-dependent fibroblast activation.

    Directory of Open Access Journals (Sweden)

    Melissa Gillette

    increased ECM gene expression and SMAD2 phosphorylation were blocked by treatment with a TGF-β receptor inhibitor. Taken together, these data suggest that p190B overexpression in the mammary epithelium induces fibroblast activation via elevated TGF-β paracrine signaling.

  10. Loss of hypoxia-inducible factor 2 alpha in the lung alveolar epithelium of mice leads to enhanced eosinophilic inflammation in cobalt-induced lung injury.

    Science.gov (United States)

    Proper, Steven P; Saini, Yogesh; Greenwood, Krista K; Bramble, Lori A; Downing, Nathaniel J; Harkema, Jack R; Lapres, John J

    2014-02-01

    Hard metal lung disease (HMLD) is an occupational lung disease specific to inhalation of cobalt-containing particles whose mechanism is largely unknown. Cobalt is a known hypoxia mimic and stabilizer of the alpha subunits of hypoxia-inducible factors (HIFs). Previous work revealed that though HIF1α contrib utes to cobalt toxicity in vitro, loss of HIF1α in the alveolar epithelial cells does not provide in vivo protection from cobalt-induced lung inflammation. HIF1α and HIF2α show unique tissue expression profiles, and HIF2α is known to be the predominant HIF mRNA isoform in the adult lung. Thus, if HIF2α activation by cobalt contributes to pathophysiology of HMLD, we hypothesized that loss of HIF2α in lung epithelium would provide protection from cobalt-induced inflammation. Mice with HIF2α-deficiency in Club and alveolar type II epithelial cells (ATIIs) (HIF2α(Δ/Δ)) were exposed to cobalt (60 µg/day) or saline using a subacute occupational exposure model. Bronchoalveolar lavage cellularity, cytokines, qRT-PCR, and histopathology were analyzed. Results show that loss of HIF2α leads to enhanced eosinophilic inflammation and increased goblet cell metaplasia. Additionally, control mice demonstrated a mild recovery from cobalt-induced lung injury compared with HIF2α(Δ/Δ) mice, suggesting a role for epithelial HIF2α in repair mechanisms. The expression of important cytokines, such as interleukin (IL)-5 and IL-10, displayed significant differences following cobalt exposure when HIF2α(Δ/Δ) and control mice were compared. In summary, our data suggest that although loss of HIF2α does not afford protection from cobalt-induced lung inflammation, epithelial HIF2α signaling does play an important role in modulating the inflammatory and repair response in the lung.

  11. Scoliosis and bronchial obstruction.

    Science.gov (United States)

    Qiabi, Mehdi; Chagnon, Karine; Beaupré, Alain; Hercun, Julian; Rakovich, George

    2015-01-01

    Severe scoliosis may have a significant effect on respiratory function. The effect is most often restrictive due to severe anatomical distortion of the chest, leading to reduced lung volumes, limited diaphragmatic excursion and chest wall muscle inefficiency. Bronchial compression by the deformed spine may also occur but is more unusual. Management options include a conservative approach using bracing and physiotherapy in mild cases, as well as surgical correction of the scoliosis in more severe cases. Bronchial stenting has also been used successfully as an alternative to surgical correction, and in cases in which spinal surgery was either unsuccessful or not feasible. The authors present a case involving a 52-year-old woman who exhibited symptomatic compression of the bronchus intermedius by severe residual scoliosis despite previous corrective surgery. She was treated with an indwelling bronchial stent.

  12. Scoliosis and Bronchial Obstruction

    Directory of Open Access Journals (Sweden)

    Mehdi Qiabi

    2015-01-01

    Full Text Available Severe scoliosis may have a significant effect on respiratory function. The effect is most often restrictive due to severe anatomical distortion of the chest, leading to reduced lung volumes, limited diaphragmatic excursion and chest wall muscle inefficiency. Bronchial compression by the deformed spine may also occur but is more unusual. Management options include a conservative approach using bracing and physiotherapy in mild cases, as well as surgical correction of the scoliosis in more severe cases. Bronchial stenting has also been used successfully as an alternative to surgical correction, and in cases in which spinal surgery was either unsuccessful or not feasible. The authors present a case involving a 52-year-old woman who exhibited symptomatic compression of the bronchus intermedius by severe residual scoliosis despite previous corrective surgery. She was treated with an indwelling bronchial stent.

  13. CpG DNA modulates interleukin 1β-induced interleukin-8 expression in human bronchial epithelial (16HBE14o- cells

    Directory of Open Access Journals (Sweden)

    Wong Hector R

    2006-06-01

    Full Text Available Abstract Background Recognition of repeat unmethylated CpG motifs from bacterial DNA through Toll-like receptor (TLR-9 has been shown to induce interleukin (IL-8 expression in immune cells. We sought to investigate the role of CpG oligodeoxynucleotides (ODN on a human bronchial epithelial cells. Methods RT-PCR and Western blot analysis were used to determine expression of TLR-9 in human bronchial epithelial cells (16HBE14o-. Cells were treated with CpG ODN in the presence or absence of IL-1β and IL-8 protein was determined using ELISA. In some cases cells were pretreated with chloroquine, an inhibitor of TLR-9 signaling, or SB202190, an inhibitor of the mitogen activated protein kinase p38, prior to treatment with IL-1β and CpG. TLR9 siRNA was used to silence TLR9 prior to treatment with IL-1β and CpG. IκBα and p38 were assessed by Western blot, and EMSA's were performed to determine NF-κB activation. To investigate IL-8 mRNA stability, cells were treated with IL-1β in the absence or presence of CpG for 2 h and actinomycin D was added to induce transcriptional arrest. Cells were harvested at 15 min intervals and Northern blot analysis was performed. Results TLR-9 is expressed in 16HBE14o- cells. CpG synergistically increased IL-1β-induced IL-8 protein abundance, however treatment with CpG alone had no effect. CpC (a control ODN had no effect on IL-1β-induced IL-8 levels. In addition, CpG synergistically upregulated TNFα-induced IL-8 expression. Silencing TLR9 using siRNA or pretreatment of cells with chloroquine had little effect on IL-1β-induced IL-8 levels, but abolished CpG-induced synergy. CpG ODN had no effect on NF-κB translocation or DNA binding in 16HBE14o- cells. Treatment with CpG increased phosphorylation of p38 and pretreatment with the p38 inhibitor SB202190 attenuated the synergistic increase in IL-8 protein levels. Analysis of the half-life of IL-8 mRNA revealed that IL-8 mRNA had a longer half-life following the co

  14. Proinflammatory cytokines induce bronchial hyperplasia and squamous metaplasia in smokers: implications for chronic obstructive pulmonary disease therapy.

    Science.gov (United States)

    Herfs, Michael; Hubert, Pascale; Poirrier, Anne-Lise; Vandevenne, Patricia; Renoux, Virginie; Habraken, Yvette; Cataldo, Didier; Boniver, Jacques; Delvenne, Philippe

    2012-07-01

    Tracheobronchial squamous metaplasia is common in smokers, and is associated with both airway obstruction in chronic obstructive pulmonary disease (COPD) and increased risk of lung cancer. Although this reversible epithelial replacement is almost always observed in association with chronic inflammation, the role of inflammatory mediators in the pathogenesis of squamous metaplasia remains unclear. In the present study, we investigated the implication of cigarette smoke-mediated proinflammatory cytokine up-regulation in the development and treatment of tracheobronchial epithelial hyperplasia and squamous metaplasia. Using immunohistological techniques, we showed a higher epithelial expression of TNF-α, IL-1β, and IL-6, as well as an activation of NF-κB and activator protein-1/mitogen-activated protein kinase signaling pathways in the respiratory tract of smoking patients, compared with the normal ciliated epithelium of nonsmoking patients. In addition, we demonstrated that these signaling pathways strongly influence the proliferation and differentiation state of in vitro-generated normal human airway epithelial basal cells. Finally, we exposed mice to cigarette smoke for 16 weeks, and demonstrated that anti-TNF-α (etanercept), anti-IL-1β (anakinra), and/or anti-IL-6R (tocilizumab) therapies significantly reduced epithelial hyperplasia and the development of squamous metaplasia. These data highlight the importance of soluble inflammatory mediators in the pathogenesis of tracheobronchial squamous metaplasia. Therefore, the administration of proinflammatory cytokine antagonists may have clinical applications in the management of patients with COPD.

  15. Cytochrome P450 2A13 enhances the sensitivity of human bronchial epithelial cells to aflatoxin B1-induced DNA damage

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Xuejiao [Key Lab of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, 818 East Tiangyuan Rd., Nanjing 211166 (China); Jiaojiang District Center for Disease Control and Prevention, 518 Jingdong Rd., Taizhou 318000 (China); Zhang, Zhan; Wang, Xichen; Wang, Yun; Zhang, Xiaoming; Lu, Huiyuan [Key Lab of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, 818 East Tiangyuan Rd., Nanjing 211166 (China); Wang, Shou-Lin, E-mail: wangshl@njmu.edu.cn [Key Lab of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, 818 East Tiangyuan Rd., Nanjing 211166 (China)

    2013-07-15

    Cytochrome P450 2A13 (CYP2A13) mainly expresses in human respiratory system and mediates the metabolic activation of aflatoxin B1 (AFB1). Our previous study suggested that CYP2A13 could increase the cytotoxic and apoptotic effects of AFB1 in immortalized human bronchial epithelial cells (BEAS-2B). However, the role of CYP2A13 in AFB1-induced DNA damage is unclear. Using BEAS-2B cells that stably express CYP2A13 (B-2A13), CYP1A2 (B-1A2), and CYP2A6 (B-2A6), we compared their effects in AFB1-induced DNA adducts, DNA damage, and cell cycle changes. BEAS-2B cells that were transfected with vector (B-vector) were used as a control. The results showed that AFB1 (5–80 nM) dose- and time-dependently induced DNA damage in B-2A13 cells. AFB1 at 10 and 80 nM significantly augmented this effect in B-2A13 and B-1A2 cells, respectively. B-2A6 cells showed no obvious DNA damage, similar to B-vector cells and the vehicle control. Similarly, compared with B-vector, B-1A2 or B-2A6 cells, B-2A13 cells showed more sensitivity in AFB1-induced γH2AX expression, DNA adduct 8-hydroxy-deoxyguanosine formation, and S-phase cell-cycle arrest. Furthermore, AFB1 activated the proteins related to DNA damage responses, such as ATM, ATR, Chk2, p53, BRCA1, and H2AX, rather than the proteins related to DNA repair. These effects could be almost completely inhibited by 100 μM nicotine (a substrate of CYP2A13) or 1 μM 8-methoxypsoralen (8-MOP; an inhibitor of CYP enzyme). Collectively, these findings suggest that CYP2A13 plays an important role in low-concentration AFB1-induced DNA damage, possibly linking environmental airborne AFB1 to genetic injury in human respiratory system. - Highlights: • CYP2A13 plays a critical role in low concentration of AFB1-induced DNA damage. • B-2A13 cells were more sensitive to AFB1 than B-1A2 cells and B-2A6 cells. • AFB1 dose- and time-dependently induced DNA damage in B-2A13 cells • AFB1-induced DNA adducts and damage can be inhibited by nicotine and 8

  16. Pandemic H1N1 influenza A directly induces a robust and acute inflammatory gene signature in primary human bronchial epithelial cells downstream of membrane fusion

    Energy Technology Data Exchange (ETDEWEB)

    Paquette, Stéphane G. [Division of Experimental Therapeutics, Toronto General Hospital Research Institute, University Health Network, Toronto, Ontario (Canada); Institute of Medical Science, Faculty of Medicine, University of Toronto, Toronto, Ontario (Canada); Banner, David [Division of Experimental Therapeutics, Toronto General Hospital Research Institute, University Health Network, Toronto, Ontario (Canada); Chi, Le Thi Bao [Department of Microbiology, Hue University of Medicine and Pharmacy, Thua Thien Hue (Viet Nam); Carlo Urbani Centre, Hue University of Medicine and Pharmacy, Thua Thien Hue (Viet Nam); Leon, Alberto J. [Division of Experimental Therapeutics, Toronto General Hospital Research Institute, University Health Network, Toronto, Ontario (Canada); International Institute of Infection and Immunity, Shantou University Medical College, Shantou, Guangdong (China); Xu, Luoling; Ran, Longsi [Division of Experimental Therapeutics, Toronto General Hospital Research Institute, University Health Network, Toronto, Ontario (Canada); Huang, Stephen S.H. [Division of Experimental Therapeutics, Toronto General Hospital Research Institute, University Health Network, Toronto, Ontario (Canada); Department of Immunology, Faculty of Medicine, University of Toronto, Toronto, Ontario (Canada); Farooqui, Amber [Division of Experimental Therapeutics, Toronto General Hospital Research Institute, University Health Network, Toronto, Ontario (Canada); International Institute of Infection and Immunity, Shantou University Medical College, Shantou, Guangdong (China); and others

    2014-01-05

    Pandemic H1N1 influenza A (H1N1pdm) elicits stronger pulmonary inflammation than previously circulating seasonal H1N1 influenza A (sH1N1), yet mechanisms of inflammatory activation in respiratory epithelial cells during H1N1pdm infection are unclear. We investigated host responses to H1N1pdm/sH1N1 infection and virus entry mechanisms in primary human bronchial epithelial cells in vitro. H1N1pdm infection rapidly initiated a robust inflammatory gene signature (3 h post-infection) not elicited by sH1N1 infection. Protein secretion inhibition had no effect on gene induction. Infection with membrane fusion deficient H1N1pdm failed to induce robust inflammatory gene expression which was rescued with restoration of fusion ability, suggesting H1N1pdm directly triggered the inflammatory signature downstream of membrane fusion. Investigation of intra-virion components revealed H1N1pdm viral RNA (vRNA) triggered a stronger inflammatory phenotype than sH1N1 vRNA. Thus, our study is first to report H1N1pdm induces greater inflammatory gene expression than sH1N1 in vitro due to direct virus–epithelial cell interaction. - Highlights: • We investigated H1N1pdm/sH1N1 infection in primary epithelial cells. • H1N1pdm directly initiated a robust inflammatory gene signature, sH1N1 did not. • H1N1pdm viral RNA triggered a stronger response than sH1N1. • H1N1pdm induces greater response due to direct virus–cell interaction. • These results have potential to impact vaccine and therapeutic development.

  17. Bronchial malignant melanoma.

    Science.gov (United States)

    Weshler, Z; Sulkes, A; Kopolovitch, J; Leviatan, A; Shifrin, E

    1980-01-01

    We describe a case of malignant melanoma presenting initially as an endobronchial lesion located in the left main bronchus causing total atelectasis. This resolved with radiation therapy. Widespread metastases developed shortly thereafter. The differential diagnosis of primary and metastatic bronchial malignant melanoma is discussed. Other isolated case reports are reviewed.

  18. Reflexology and bronchial asthma

    DEFF Research Database (Denmark)

    Brygge, T; Heinig, J H; Collins, P

    2001-01-01

    Many asthma patients seek alternative or adjunctive therapies. One such modality is reflexology, whereby finger pressure is applied to certain parts of the body. The aim of the study was to examine the popular claim that reflexology treatment benefits bronchial asthma. Ten weeks of active...

  19. AKT1E¹⁷K Is Oncogenic in Mouse Lung and Cooperates with Chemical Carcinogens in Inducing Lung Cancer.

    Science.gov (United States)

    Malanga, Donatella; Belmonte, Stefania; Colelli, Fabiana; Scarfò, Marzia; De Marco, Carmela; Oliveira, Duarte Mendes; Mirante, Teresa; Camastra, Caterina; Gagliardi, Monica; Rizzuto, Antonia; Mignogna, Chiara; Paciello, Orlando; Papparella, Serenella; Fagman, Henrik; Viglietto, Giuseppe

    2016-01-01

    The hotspot AKT1E17K mutation in the pleckstrin homology domain of AKT1 occurs in approximately 0.6-2% of human lung cancers. Recently, we have demonstrated that AKT1E17K transforms immortalized human bronchial cells. Here by use of a transgenic Cre-inducible murine strain in the wild type Rosa26 (R26) locus (R26-AKT1E17K mice) we demonstrate that AKT1E17K is a bona-fide oncogene and plays a role in the development of lung cancer in vivo. In fact, we report that mutant AKT1E17K induces bronchial and/or bronchiolar hyperplastic lesions in murine lung epithelium, which progress to frank carcinoma at very low frequency, and accelerates tumor formation induced by chemical carcinogens. In conclusion, AKT1E17K induces hyperplasia of mouse lung epithelium in vivo and cooperates with urethane to induce the fully malignant phenotype.

  20. Uptake of 12-HETE by human bronchial epithelial cells (HBEC): effects on HBEC cytokine production.

    Science.gov (United States)

    Gormand, F; Chabannes, B; Moliere, P; Perrin-Fayolle, M; Lagarde, M; Pacheco, Y

    1996-04-01

    12-HETE, the major lipoxygenase end-product of platelets and macrophages, may be released in contact of bronchial epithelium in inflammatory diseases of the lung. We have studied the outcome of 12-HETE in presence of human bronchial epithelial cells (HBEC). When HBEC were incubated with [3H]12-HETE for 30 minutes, 27.5% of total radioactivity was found in HBEC and 72.5% in supernatants. Unesterified 12-HETE accounted for 22.4% of total radioactivity, 4.5% being recovered in phospholipids, preferentially in phosphatidylcholine and phosphatidylethanolamine. No incorporation in neutral lipids was detected. 72.9% of the incubated radioactivity was recovered in un identified metabolites. As 12-HETE has been shown to modulate the expression and production of various proteins, the consequence of the 12-HETE uptake on the release of GM-CSF and IL8 by HBEC was assessed. HBEC from control subjects were cultured for 24 hours with 12-HETE (10(-9) to 10(-7)M) in the presence or absence of TNF alpha. Detectable amounts of both cytokines were released in the supernatant in basal conditions at 24hr, and TNF alpha increased significantly the release of GM-CSF. 12-HETE at 10(-7)M weakly but significantly decreased the TNF-induced release of GM-CSF from HBEC. Thus the uptake of 12-HETE could affect the epithelial cell function in some situations.

  1. A CHARACTERIZATION OF INFLAMMATORY AND STRUCTURAL MARKERS WITHIN THE RUMEN EPITHELIUM DURING GRAIN-INDUCED RUMINAL ACIDOSIS IN LACTATING DAIRY CATTLE

    Directory of Open Access Journals (Sweden)

    L. Dionissopoulos

    2012-01-01

    Full Text Available The objective of this study was to characterize the mRNA and protein expression of inflammatory and structural genes in the rumen epithelium during grain-induced ruminal acidosis in lactating dairy cattle. A total of 16 rumen-fistulated, lactating Holstein dairy cattle (618±35 kg of body weight, 221±32 days in milk were used in a randomized complete block design study. All cattle were initially fed a high-forage diet (HF; 88.9% of dry matter and after a baseline (wk 0 measurement, half of the cattle were randomly assigned and transitioned to a high-concentrate diet (HC; 62.2% of dry matter which was fed for 3 weeks (weeks 1, 2 and 3. Continuous ruminal pH, ruminal LPS and plasma LPS-binding protein were measured each week followed by a rumen papillae biopsy used for mRNA and protein quantification. After the baseline period, ruminal LPS was higher in HC compared to HF cattle (28851±6905 vs. 5771±3042 EU mL-1. There was no difference in mRNA expression of inflammatory and structure genes in rumen papillae between HF and HC cattle during all weeks. With regard to protein expression, there was an up regulation (p = 0.02 of nuclear factor of activated T-cells cytoplasmic 2 expression during weeks 1, 2 and 3; however, all other inflammatory markers within the rumen epithelium were unchanged by treatment. These results suggest that although grain-induced ruminal acidosis leads to characteristic whole-animal inflammatory response, only marginal changes in inflammatory and structural gene and protein expression in the rumen epithelium were detected.

  2. Macrophages promote benzopyrene-induced tumor transformation of human bronchial epithelial cells by activation of NF-κB and STAT3 signaling in a bionic airway chip culture and in animal models.

    Science.gov (United States)

    Li, Encheng; Xu, Zhiyun; Zhao, Hui; Sun, Zhao; Wang, Lei; Guo, Zhe; Zhao, Yang; Gao, Zhancheng; Wang, Qi

    2015-04-20

    We investigated the role of macrophages in promoting benzopyrene (BaP)-induced malignant transformation of human bronchial epithelial cells using a BaP-induced tumor transformation model with a bionic airway chip in vitro and in animal models. The bionic airway chip culture data showed that macrophages promoted BaP-induced malignant transformation of human bronchial epithelial cells, which was mediated by nuclear factor (NF)-κB and STAT3 pathways to induce cell proliferation, colony formation in chip culture, and tumorigenicity in nude mice. Blockage of interleukin (IL)-6 or tumor necrosis factor (TNF)-α signaling or inhibition of NF-κB, STAT3, or cyclinD1 expression abrogated the effect of macrophages on malignant transformation in the bionic airway chip culture. In vivo, macrophages promoted lung tumorigenesis in a carcinogen-induced animal model. Similarly, blockage of NF-κB, STAT3, or cyclinD1 using siRNA transfection decreased the carcinogen-induced tumorigenesis in rats. We demonstrated that macrophages are critical in promoting lung tumorigenesis and that the macrophage-initiated TNF-α/NF-κB/cyclinD1 and IL-6/STAT3/cyclinD1 pathways are primarily responsible for promoting lung tumorigenesis.

  3. Cigarette smoke causes caspase-independent apoptosis of bronchial epithelial cells from asthmatic donors.

    Directory of Open Access Journals (Sweden)

    Fabio Bucchieri

    Full Text Available Epidemiologic studies have demonstrated important links between air pollution and asthma. Amongst these pollutants, environmental cigarette smoke is a risk factor both for asthma pathogenesis and exacerbation. As the barrier to the inhaled environment, the bronchial epithelium is a key structure that is exposed to cigarette smoke.Since primary bronchial epithelial cells (PBECs from asthmatic donors are more susceptible to oxidant-induced apoptosis, we hypothesized that they would be susceptible to cigarette smoke-induced cell death.PBECs from normal and asthmatic donors were exposed to cigarette smoke extract (CSE; cell survival and apoptosis were assessed by fluorescence-activated cell sorting, and protective effects of antioxidants evaluated. The mechanism of cell death was evaluated using caspase inhibitors and immunofluorescent staining for apoptosis-inducing factor (AIF.Exposure of PBEC cultures to CSE resulted in a dose-dependent increase in cell death. At 20% CSE, PBECs from asthmatic donors exhibited significantly more apoptosis than cells from non-asthmatic controls. Reduced glutathione (GSH, but not ascorbic acid (AA, protected against CSE-induced apoptosis. To investigate mechanisms of CSE-induced apoptosis, caspase-3 or -9 inhibitors were tested, but these failed to prevent apoptosis; in contrast, CSE promoted nuclear translocation of AIF from the mitochondria. GSH reduced the number of nuclear-AIF positive cells whereas AA was ineffective.Our results show that PBECs from asthmatic donors are more susceptible to CSE-induced apoptosis. This response involves AIF, which has been implicated in DNA damage and ROS-mediated cell-death. Epithelial susceptibility to CSE may contribute to the impact of environmental tobacco smoke in asthma.

  4. Influenza H5N1 and H1N1 virus replication and innate immune responses in bronchial epithelial cells are influenced by the state of differentiation.

    Directory of Open Access Journals (Sweden)

    Renee W Y Chan

    Full Text Available Influenza H5N1 virus continues to be enzootic in poultry and transmits zoonotically to humans. Although a swine-origin H1N1 virus has emerged to become pandemic, its virulence for humans remains modest in comparison to that seen in zoonotic H5N1 disease. As human respiratory epithelium is the primary target cells for influenza viruses, elucidating the viral tropism and host innate immune responses of influenza H5N1 virus in human bronchial epithelium may help to understand the pathogenesis. Here we established primary culture of undifferentiated and well differentiated normal human bronchial epithelial (NHBE cells and infected with highly pathogenic influenza H5N1 virus (A/Vietnam/3046/2004 and a seasonal influenza H1N1 virus (A/Hong Kong/54/1998, the viral replication kinetics and cytokine and chemokine responses were compared by qPCR and ELISA. We found that the in vitro culture of the well differentiated NHBE cells acquired the physiological properties of normal human bronchi tissue which express high level of alpha2-6-linked sialic acid receptors and human airway trypsin-like (HAT protease, in contrast to the low expression in the non-differentiated NHBE cells. When compared to H1N1 virus, the H5N1 virus replicated more efficiently and induced a stronger type I interferon response in the undifferentiated NHBE cells. In contrast, in well differentiated cultures, H5N1 virus replication was less efficient and elicited a lower interferon-beta response in comparison with H1N1 virus. Our data suggest that the differentiation of bronchial epithelial cells has a major influence in cells' permissiveness to human H1N1 and avian H5N1 viruses and the host innate immune responses. The reduced virus replication efficiency partially accounts for the lower interferon-beta responses in influenza H5N1 virus infected well differentiated NHBE cells. Since influenza infection in the bronchial epithelium will lead to tissue damage and associate with the

  5. Tgm2/Gh, Gbx1 and TGF-beta are involved in retinoic acid-induced transdifferentiation from epidermis to mucosal epithelium.

    Science.gov (United States)

    Obinata, Akiko; Osakabe, Keitarou; Yamaguchi, Mari; Morimoto, Riyo; Akimoto, Yoshihiro

    2011-01-01

    We previously demonstrated that retinoic acid (RA) induces epidermis to transdifferentiate to mucosal epithelium with goblet cells in chick embryonic cultured skin. To characterize the molecular mechanism of this transdifferentiation process, we used rat embryonic cultured skin and immunohistochemistry to confirm that RA-induced epidermal transdifferentiation accompanies the expression of markers of esophagus epithelium. Because Gbx1, TG2/Gh (transglutaminase2) and TGF-beta2 are reported individually to be induced by RA in cultures of chick embryonic skin, mouse epidermal cells and human hair follicles respectively, here, we investigated whether cooperative interplay of Gbx1, TG2/Gh and TGF-beta2 is required for the transdifferentiation of epidermal cells to mucosal cells. We have shown that expression of Gbx1, TG2/Gh and TGF-beta proteins were all upregulated in RA-induced transdifferentiated skin and that the former two were expressed in the epidermis, while TGF-beta was expressed in the dermis. Inhibitors of the TGF-beta signal pathway partially inhibited transdifferentiation. Overexpression of both hTG2/Gh and mGbx1 together in the epidermis by electroporation resulted in cuboidal cells in the upper cell layers of the epidermis without keratinized layers, although epidermal keratinization was observed in skin by overexpression of either of them. Labeling DNA with BrdU indicated that RA directly transdifferentiated transient amplifying epidermal cells, not stem cells, to mucosal cells. This study showed that coexpression of TG/2 and Gbx1 in the epidermis was required for esophagus-like mucosal transdifferentiation, and that increase in TGF-beta2 expression by RA in the dermis was essential to induce transdifferentiation through epithelial-mesenchymal interaction.

  6. Characterization of protocadherin-1 expression in primary bronchial epithelial cells : association with epithelial cell differentiation

    NARCIS (Netherlands)

    Koning, Henk; Sayers, Ian; Stewart, Ceri E.; de Jong, Debora; ten Hacken, Nick H. T.; Postma, Dirkje S.; van Oosterhout, Antoon J. M.; Nawijn, Martijn C.; Koppelman, Gerard H.

    2012-01-01

    Protocadherin-1 (PCDH1) is a novel susceptibility gene for asthma that is expressed in airway epithelium. We aimed to characterize PCDH1 mRNA transcripts and protein expression in primary bronchial epithelial cells and to determine regulation of PCDH1 during mucociliary differentiation. Total RNA an

  7. Transcriptional response of bronchial epithelial cells to Pseudomonas aeruginosa: identification of early mediators of host defense.

    NARCIS (Netherlands)

    Vos, J.B.; Sterkenburg, M.A. van; Rabe, K.F.; Schalkwijk, J.; Hiemstra, P.S.; Datson, N.A.

    2005-01-01

    The airway epithelium responds to microbial exposure by altering expression of a variety of genes to increase innate host defense. We aimed to delineate the early transcriptional response in human primary bronchial epithelial cells exposed for 6 h to a mixture of IL-1beta and TNF-alpha or heat-inact

  8. Bronchial Thermoplasty in Asthma

    Directory of Open Access Journals (Sweden)

    Wayne Mitzner

    2006-01-01

    Full Text Available In this review we discuss the potential of a new procedure, termed Bronchial Thermoplasty to prevent serious consequences resulting from excessive airway narrowing. The most important factor in minimizing an asthmatic attack is limiting the degree of smooth muscle shortening. The premise that airway smooth muscle can be either inactivated or obliterated without any long-term alteration of other lung tissues, and that airway function will remain normal, albeit with reduced bronchoconstriction, has now been demonstrated in dogs, a subset of normal subjects, and mild asthmatics. Bronchial Thermoplasty may thus develop into a useful clinical procedure to effectively impair the ability for airway smooth muscle to reach the levels of pathologic narrowing that characterizes an asthma attack. It may also enable more successful treatment of asthma patients who are unresponsive to more conventional therapies. Whether this will remain stable for the lifetime of the patient still remains to be determined, but at the present time, there are no indications that the smooth muscle contractility will return. This successful preliminary experience showing that Bronchial Thermoplasty could be safely performed in patients with asthma has led to an ongoing clinical trial at a number of sites in Europe and North America designed to examine the effectiveness of this procedure in subjects with moderately severe asthma.

  9. Mineralocorticoid receptor stimulation induces urinary storage dysfunction via upregulation of epithelial sodium channel expression in the rat urinary bladder epithelium.

    Science.gov (United States)

    Yamamoto, Seiji; Hotta, Yuji; Maeda, Kotomi; Kataoka, Tomoya; Maeda, Yasuhiro; Hamakawa, Takashi; Sasaki, Shoichi; Yasui, Takahiro; Asai, Kiyofumi; Kimura, Kazunori

    2016-04-01

    We aimed to evaluate mineralocorticoid receptor (MR) expression in rat bladder and the physiological role of the MR-epithelial sodium channel (ENaC) pathway in controlling bladder function in 10-12-week-old, male Sprague-Dawley rats. First, we examined the mRNA expression of MR and localization of MR and ENaC-α proteins in the urinary bladder. MR mRNA expression was observed in untreated-rat urinary bladders, and MR and ENaC-α proteins were localized in the epithelium. Next, rats were treated with vehicle (controls) or fludrocortisone (an MR agonist) for 3 days, and ENaC-α protein expression levels and bladder function were evaluated on day 4. ENaC-α protein expression was significantly higher in fludrocortisone-treated rats than in controls. In addition, cystometry was performed during intravesical infusion of saline and amiloride (an ENaC inhibitor). While intercontraction intervals (ICIs) during saline infusion were significantly shorter in the fludrocortisone group than in the controls, infusion of amiloride normalized the ICIs in the fludrocortisone group. However, no intra- or inter-group differences in maximum intravesical pressure were observed. Taken together, MR protein is localized in the rat urinary bladder epithelium, and may regulate ENaC expression and bladder afferent input. The MR-ENaC pathway may be a therapeutic target for ameliorating storage symptoms.

  10. Flagellin of Pseudomonas aeruginosa induces transforming growth factor beta 1 expression in normal bronchial epithelial cells through mitogen activated protein kinase cascades

    Institute of Scientific and Technical Information of China (English)

    YANG Jing-jing; WANG Dan-dan; SUN Tie-ying

    2011-01-01

    flagellin vs. Control groups ((104.3±20.8) vs.(44.6±4.4) pg/ml (P <0.01)) and was ablated by either p38 or JNK inhibitors compared with flagellin treatment ((45.1±18.8)vs. (104.3±20.8) pg/ml and (48.1±20.8) vs. (104.3±20.8) pg/ml, respectively (P <0.05)). Flagellin also elevated the expression of IL-8 in BEAS-2B cells vs. The control groups ((554.9±57.7) vs. (51.4±2.2.9) pg/ml (P <0.01)), and p38 MAPK inhibitors weaken the expression by flagellin ((301.1 ±155.1) vs. (554.9±57.7) pg/ml (P <0.05)). Western blotting revealed that all three MAPK proteins, p38, JNK and ERK were activated by flagellin challenge in an early phase, respectively in 15 minutes (P <0.01), 30 minutes (P <0.01) and 15 minutes (P <0.01). TRAF6 siRNA which decreased expression of TRAF6, altered the activation of JNK, p38, and ERK following flagellin treatment, but its influence on the expression of TGF-β1 and IL-8 has no statistical significance.Conclusions Flagellin from P. Aeruginosa PAO1 induces TGF-β1 expression in normal bronchial epithelial cells,BEAS-2B, through the MAPK signal cascade in vitro. It suggests that the fibrogenesis/remodeling process may be initiated from an early stage of acute lung infection due to P. Aeruginosa.

  11. [Bronchial morphologic modification in asthma].

    Science.gov (United States)

    Cataldo, D; Louis, R; Godon, A; Munaut, C; Noël, A; Foidart, J M; Bartsch, P

    2000-07-01

    Asthma is an inflammatory disease of the airways clinically characterised by recurrent bronchial obstructions at least partially reversible. Recent epidemiologic data suggest that asthmatics have an increased rate of decrease of their expiratory volumes during life. This irreversible lung function impairment is associated with fundamental structural changes of the bronchial wall in terms of conjunctive tissue and smooth muscle composition. We describe these changes and explore the different mechanisms proposed to explain these structural modifications. We also review their consequences in terms of bronchial physiology and their potential influence on bronchial hyperresponsiveness.

  12. Engineering Airway Epithelium

    Directory of Open Access Journals (Sweden)

    John P. Soleas

    2012-01-01

    Full Text Available Airway epithelium is constantly presented with injurious signals, yet under healthy circumstances, the epithelium maintains its innate immune barrier and mucociliary elevator function. This suggests that airway epithelium has regenerative potential (I. R. Telford and C. F. Bridgman, 1990. In practice, however, airway regeneration is problematic because of slow turnover and dedifferentiation of epithelium thereby hindering regeneration and increasing time necessary for full maturation and function. Based on the anatomy and biology of the airway epithelium, a variety of tissue engineering tools available could be utilized to overcome the barriers currently seen in airway epithelial generation. This paper describes the structure, function, and repair mechanisms in native epithelium and highlights specific and manipulatable tissue engineering signals that could be of great use in the creation of artificial airway epithelium.

  13. β1- and β2-adrenergic stimulation-induced electrogenic transport by human endolymphatic sac epithelium and its clinical implications

    Science.gov (United States)

    Kim, Bo Gyung; Kim, Jin Young; Jung, JinSei; Moon, In Seok; Yoon, Joo-Heon; Choi, Jae Young; Kim, Sung Huhn

    2017-01-01

    The endolymphatic sac (ES) is a cystic structure of the inner ear connected to the cochlea and vestibule, which plays a role in regulating ion homeostasis in inner ear fluid. Disruption of ion homeostasis can cause inner ear disorders with hearing loss and dizziness, such as Meniere’s disease. Herein, we found, for the first time, functional evidence for the involvement of β1- and β2-adrenergic receptors in apical electrogenic ion transport by human ES epithelium by using electrophysiological/pharmacological and molecular biological methods, which were dependent on K+ and Cl− ion transport. The apical electrogenic transport was absent or very weak in ES epithelia of patients with Meniere’s disease. These results suggested that adrenergic stimulation via β1- and β2-adrenergic receptors in the human ES was involved in regulation of inner ear fluid ion homeostasis and impairment of this response could be a pathological mechanism of Meniere’s disease. PMID:28165045

  14. HIV Impairs Lung Epithelial Integrity and Enters the Epithelium to Promote Chronic Lung Inflammation.

    Science.gov (United States)

    Brune, Kieran A; Ferreira, Fernanda; Mandke, Pooja; Chau, Eric; Aggarwal, Neil R; D'Alessio, Franco R; Lambert, Allison A; Kirk, Gregory; Blankson, Joel; Drummond, M Bradley; Tsibris, Athe M; Sidhaye, Venkataramana K

    2016-01-01

    Several clinical studies show that individuals with HIV are at an increased risk for worsened lung function and for the development of COPD, although the mechanism underlying this increased susceptibility is poorly understood. The airway epithelium, situated at the interface between the external environment and the lung parenchyma, acts as a physical and immunological barrier that secretes mucins and cytokines in response to noxious stimuli which can contribute to the pathobiology of chronic obstructive pulmonary disease (COPD). We sought to determine the effects of HIV on the lung epithelium. We grew primary normal human bronchial epithelial (NHBE) cells and primary lung epithelial cells isolated from bronchial brushings of patients to confluence and allowed them to differentiate at an air- liquid interface (ALI) to assess the effects of HIV on the lung epithelium. We assessed changes in monolayer permeability as well as the expression of E-cadherin and inflammatory modulators to determine the effect of HIV on the lung epithelium. We measured E-cadherin protein abundance in patients with HIV compared to normal controls. Cell associated HIV RNA and DNA were quantified and the p24 viral antigen was measured in culture supernatant. Surprisingly, X4, not R5, tropic virus decreased expression of E-cadherin and increased monolayer permeability. While there was some transcriptional regulation of E-cadherin, there was significant increase in lysosome-mediated protein degradation in cells exposed to X4 tropic HIV. Interaction with CXCR4 and viral fusion with the epithelial cell were required to induce the epithelial changes. X4 tropic virus was able to enter the airway epithelial cells but not replicate in these cells, while R5 tropic viruses did not enter the epithelial cells. Significantly, X4 tropic HIV induced the expression of intercellular adhesion molecule-1 (ICAM-1) and activated extracellular signal-regulated kinase (ERK). We demonstrate that HIV can enter airway

  15. HIV Impairs Lung Epithelial Integrity and Enters the Epithelium to Promote Chronic Lung Inflammation.

    Directory of Open Access Journals (Sweden)

    Kieran A Brune

    Full Text Available Several clinical studies show that individuals with HIV are at an increased risk for worsened lung function and for the development of COPD, although the mechanism underlying this increased susceptibility is poorly understood. The airway epithelium, situated at the interface between the external environment and the lung parenchyma, acts as a physical and immunological barrier that secretes mucins and cytokines in response to noxious stimuli which can contribute to the pathobiology of chronic obstructive pulmonary disease (COPD. We sought to determine the effects of HIV on the lung epithelium. We grew primary normal human bronchial epithelial (NHBE cells and primary lung epithelial cells isolated from bronchial brushings of patients to confluence and allowed them to differentiate at an air- liquid interface (ALI to assess the effects of HIV on the lung epithelium. We assessed changes in monolayer permeability as well as the expression of E-cadherin and inflammatory modulators to determine the effect of HIV on the lung epithelium. We measured E-cadherin protein abundance in patients with HIV compared to normal controls. Cell associated HIV RNA and DNA were quantified and the p24 viral antigen was measured in culture supernatant. Surprisingly, X4, not R5, tropic virus decreased expression of E-cadherin and increased monolayer permeability. While there was some transcriptional regulation of E-cadherin, there was significant increase in lysosome-mediated protein degradation in cells exposed to X4 tropic HIV. Interaction with CXCR4 and viral fusion with the epithelial cell were required to induce the epithelial changes. X4 tropic virus was able to enter the airway epithelial cells but not replicate in these cells, while R5 tropic viruses did not enter the epithelial cells. Significantly, X4 tropic HIV induced the expression of intercellular adhesion molecule-1 (ICAM-1 and activated extracellular signal-regulated kinase (ERK. We demonstrate that HIV

  16. Persistent disruption of ciliated epithelium following paediatric lung transplantation.

    Science.gov (United States)

    Thomas, Biju; Aurora, Paul; Spencer, Helen; Elliott, Martin; Rutman, Andrew; Hirst, Robert A; O'Callaghan, Christopher

    2012-11-01

    It is unclear whether ciliary function following lung transplantation is normal or not. Our aim was to study the ciliary function and ultrastructure of epithelium above and below the airway anastomosis and the peripheral airway of children following lung transplantation. We studied the ciliary beat frequency (CBF) and beat pattern, using high speed digital video imaging and ultrastructure by transmission electron microscopy, of bronchial epithelium from above and below the airway anastomosis and the peripheral airway of 10 cystic fibrosis (CF) and 10 non-suppurative lung disease (NSLD) paediatric lung transplant recipients. Compared to epithelium below the anastomosis, the epithelium above the anastomosis in the CF group showed reduced CBF (median (interquartile range): 10.5 (9.0-11.4) Hz versus 7.4 (6.4-9.2) Hz; pepithelium above the anastomosis, the epithelium below the anastomosis showed marked ultrastructural abnormalities (median duration post-transplant 7-12 months). Ciliary dysfunction is a feature of native airway epithelium in paediatric CF lung transplant recipients. The epithelium below the airway anastomosis shows profound ultrastructural abnormalities in both CF and NSLD lung transplant recipients, many months after transplantation.

  17. Benzo(a)pyrene and X-rays induce reversions of the pink-eyed unstable mutation in the retinal pigment epithelium of mice.

    Science.gov (United States)

    Bishop, A J; Kosaras, B; Sidman, R L; Schiestl, R H

    2000-12-20

    The pink-eyed unstable (p(un)) mutation is the result of a 70kb tandem duplication within the murine p gene. Homologous deletion/recombination of the locus to wild-type occurs spontaneously in embryos and results in pigmented spots in the fur and eye that persist for life. Such deletion events are also inducible by a variety of DNA damaging agents, as we have observed previously with the fur spot assay. Here, we describe the use of the retinal pigment epithelium (RPE) of the eye to detect reversion events induced with two differently acting agents. Benzo(a)pyrene (B(a)P) induces a high frequency, and X-ray exposure a more modest increase, of p(un) reversion in both the fur and the eye. The eye-spot assay requires fewer mice for significant results than the fur spot assay. Previous work had elucidated the cell proliferation pattern in the RPE and a position effect variegation phenotype in the pattern of p(un) reversions, which we have confirmed. Acute exposure to B(a)P or X-rays resulted in an increased frequency of reversion events. The majority of the spontaneous reversions lie toward the periphery of the RPE whereas induced events are found more centrally, closer to the optic nerve head. The induced distribution corresponds to the major sites of cell proliferation in the RPE at the time of exposure, and further advocates the proposal that dividing cells are at highest risk to develop deletions.

  18. [Bronchial mucoepidermoid carcinoma].

    Science.gov (United States)

    Bregante, J I; Rituerto, B; Font de Mora, F; Alonso, F; Andreu, M J; Figuerola, J; Mulet, J F

    1998-07-01

    We submit the case of a child afflicted with a mucoepidermoid bronchial tumor. The patient is a boy, aged seven, who after undergoing antibiotic treatment for six weeks because of a fever and atelectasia-condensation in the right lower lobe showed no signs of clinical improvement and was sent to our department to undergo further study and treatment. A bronchoscopy performed shows a polypoid mass that partially blocks the main bronchial tube a few milimiters under the access to the right upper lobe. A biopsy is carried out and the anatomopathological test shows there is a low degree epidermoid carcinoma. We decide to perform a lobectomy which for the tumor location and the lung condition has to be medium and lower right. We proceed to remove the adenopaty of hilium not affected by the tumor. The postoperative period develops without incidents. A check-up bronchoscopy performed three months later shows two polypoid masses in the right bronchial tube which, once a biopsy is performed, proved to be granulation tissue. Twelve months after undergoing surgery, the patient's condition is good, there is no evidence of tumor relapse and the breathing capacity is adequate, though there is an obstructive restrictive pattern in the espirometry. Even taking into consideration that lung tumors are extremely unusual, the epidermoid carcinoma is the one which most frequently occurs. The tumor's low malignancy is a sign that points to a good prognosis. Performing conservative surgery by means of bronchoplasty should be taken into account so as to keep the sequelae on the lung condition to a minimum, even though in this case the tumor location made it impossible.

  19. Glutamine supplementation attenuates ethanol-induced disruption of apical junctional complexes in colonic epithelium and ameliorates gut barrier dysfunction and fatty liver in mice.

    Science.gov (United States)

    Chaudhry, Kamaljit K; Shukla, Pradeep K; Mir, Hina; Manda, Bhargavi; Gangwar, Ruchika; Yadav, Nikki; McMullen, Megan; Nagy, Laura E; Rao, RadhaKrishna

    2016-01-01

    Previous in vitro studies showed that glutamine (Gln) prevents acetaldehyde-induced disruption of tight junctions and adherens junctions in Caco-2 cell monolayers and human colonic mucosa. In the present study, we evaluated the effect of Gln supplementation on ethanol-induced gut barrier dysfunction and liver injury in mice in vivo. Ethanol feeding caused a significant increase in inulin permeability in distal colon. Elevated permeability was associated with a redistribution of tight junction and adherens junction proteins and depletion of detergent-insoluble fractions of these proteins, suggesting that ethanol disrupts apical junctional complexes in colonic epithelium and increases paracellular permeability. Ethanol-induced increase in colonic mucosal permeability and disruption of junctional complexes were most severe in mice fed Gln-free diet. Gln supplementation attenuated ethanol-induced mucosal permeability and disruption of tight junctions and adherens junctions in a dose-dependent manner, indicating the potential role of Gln in nutritional intervention to alcoholic tissue injury. Gln supplementation dose-dependently elevated reduced-protein thiols in colon without affecting the level of oxidized-protein thiols. Ethanol feeding depleted reduced protein thiols and elevated oxidized protein thiols. Ethanol-induced protein thiol oxidation was most severe in mice fed with Gln-free diet and absent in mice fed with Gln-supplemented diet, suggesting that antioxidant effect is one of the likely mechanisms involved in Gln-mediated amelioration of ethanol-induced gut barrier dysfunction. Ethanol feeding elevated plasma transaminase and liver triglyceride, which was accompanied by histopathologic lesions in the liver; ethanol-induced liver damage was attenuated by Gln supplementation. These results indicate that Gln supplementation ameliorates alcohol-induced gut and liver injury.

  20. Fractura bronquial BRONCHIAL FRACTURE

    Directory of Open Access Journals (Sweden)

    IVÁN CAVIEDES S

    2003-04-01

    Full Text Available El traumatismo torácico es una entidad patológica emergente, relacionada con accidentes automovilísticos. La lesión más frecuente es la fractura costal. Dependiendo de su gravedad, éste puede provocar tórax volante, contusión cardíaca, lesiones vasculares u otras alteraciones. La ruptura bronquial se observa ocasionalmente en traumatismos torácicos cerrados, y por lo general tiene lugar en el tronco principal del árbol tráqueo-bronquial. Su diagnóstico y manejo inicial representan un problema mayor. Los signos clásicos son la persistencia de neumotórax y flujo masivo de aire a través del drenaje torácico; sin embargo también hay casos que no son típicos. Es difícil determinar el momento correcto para iniciar la ventilación mecánica con presión positiva, la que puede aumentar gravemente el flujo de aire a través de la ruptura bronquial y acentuar el neumotórax a tensión. Presentamos el caso de un hombre de 25 años con un traumatismo torácico cerrado, causado por un accidente de automóvil, en quien la broncoscopía demostró una fractura del bronquio lobar medio. Comprobamos en este paciente, que la fibrobroncoscopía es el procedimiento más útil tanto en el diagnóstico, como en el tratamiento inicial y en el seguimiento post operatorio de su fractura bronquiaThoracic trauma is an emerging pathology related to the increase of motor vehicle accidents. Rib fracture is the most frequent injury; depending on the severity of the event it may be associated with flail chest, cardiac contusion, vascular lesions and other injuries. Bronchial rupture is occasionally seen in blunt trauma and it occurs mostly in the main stem of the tracheobronchial tree. It represents a great task in diagnosis and initial management. Persistent pneumothorax and massive airflow by the thoracic drain are the classic signs, however other cases are not so typical. The right moment to begin positive pressure ventilation is challenging, because in

  1. Blockade of Jagged/Notch pathway abrogates transforming growth factor β2-induced epithelial-mesenchymal transition in human retinal pigment epithelium cells.

    Science.gov (United States)

    Chen, X; Xiao, W; Liu, X; Zeng, M; Luo, L; Wu, M; Ye, S; Liu, Y

    2014-05-01

    The epithelial-mesenchymal transition (EMT) of retinal pigment epithelium (RPE) cells plays a key role in proliferative vitreoretinopathy (PVR) and proliferative diabetic retinopathy (PDR), which lead to the loss of vision. The Jagged/Notch pathway has been reported to be essential in EMT during embryonic development, fibrotic diseases and cancer metastasis. However, the function of Jagged/Notch signaling in EMT of RPE cells is unknown. Thus, we hypothesized that a crosstalk between Notch and transforming growth factor β2 (TGF-β2) signaling could induce EMT in RPE cells, which subsequently contributes to PVR and PDR. Here, we demonstrate that Jagged-1/Notch pathway is involved in the TGF-β2-mediated EMT of human RPE cells. Blockade of Notch pathway with DAPT (a specific inhibitor of Notch receptor cleavage) and knockdown of Jagged-1 expression inhibited TGF-β2-induced EMT through regulating the expression of Snail, Slug and ZEB1. Besides the canonical Smad signaling pathway, the noncanonical PI3K/Akt and MAPK pathway also contributed to TGF-β2-induced up-regulation of Jagged-1 in RPE cells. Overexpression of Jagged-1 could mimic TGF-β2 induce EMT. Our data suggest that the Jagged-1/Notch signaling pathway plays a critical role in TGF-β2-induced EMT in human RPE cells, and may contribute to the development of PVR and PDR. Inhibition of the Jagged/Notch signaling pathway, therefore, may have therapeutic value in the prevention and treatment of PVR and PDR.

  2. Typhoid fever as a triggering factor in acute and intractable bronchial asthma attack.

    Science.gov (United States)

    Wardhana; Surachmanto, Eko E; Datau, E A

    2013-10-01

    Typhoid fever is an enteric infection caused by Salmonella typhi. In Indonesia, typhoid fever is endemic with high incidence of the disease. In daily practice we frequently have patients with bronchial asthma, and it is becoming worse when these patients get typhoid fever. After oral ingestion, Salmonella typhi invades the the intestine mucosa after conducted by microbial binding to epithelial cells, destroying the microfold cells (M cell) then passed through the lamina propria and detected by dendritic cells (DC) which express a variety of pathogen recognition receptors on the surfaces, including Toll-Like Receptor (TLR). expressed on macrophages and on intestinal epithelial cells inducing degradation of IB, and translocation of NF-B (Nuclear Factor-Kappa Beta). This process initiates the induction of pro-inflammatory gene expression profile adhesion molecules, chemokines, adhesion molecules, and other proteins that induce and perpetuate the inflammation in host cells then will induce acute ant intractable attack of bronchial asthma. The role of typhoid fever in bronchial asthma, especially in persons with acute attack of bronchial asthma, is not well understood. In this article, we will discuss the role of typhoid fever in the bronchial asthma patients which may cause bronchial asthma significantly become more severe even triggering the acute and intractable attack of bronchial asthma. This fact makes an important point, to treat completely the typhoid fever in patients with bronchial asthma.

  3. Bronchial artery embolization in hemoptysis

    Institute of Scientific and Technical Information of China (English)

    DAI Hong-xiu; YANG Ding-cai; LIU Wei-hong; TANG He-qing; LIU Ke-yong; ZHAO Xiao-hua; TAN Yi-qing; WANG Jun

    2005-01-01

    Massive hemoptysis is one of the most dreaded of all respiratory emergencies and can have a variety of underlying causes. It is mostly caused by bleeding from bronchial circulation. Bronchial artery embolization is now considered to be the treatment of choice for acute massive hemoptysis. Bronchial artery embolization (BAE) is a safe and effective nonsurgical treatment for patients with massive hemoptysis. However, nonbronchial systemic arteries can be a significant source of massive hemoptysis and a cause of recurrence after successful BAE. So knowledge of the bronchial artery anatomy, together with an understanding of the pathophysiologic features of massive hemoptysis, are essential for planning and performing BAE in affected patients. In addition, interventional radiologists should be familiar with the techniques, results, efficacy, safety and possible complications of BAE and with the characteristics of the various embolic agents. Bronchial arterial catheterisation in human via a percutaneous approach has been practiced for 32 years (1973) in the world and 20 years (1986) in China, initially for direct chemotherapy treatment for bronchial malignancies and then for the embolization of patients with massive haemoptysis. A review of clinical experience to evaluate technique,embolic materials,outcome and complications of BAE is presented.

  4. Respiratory syncytial virus inhibits ciliagenesis in differentiated normal human bronchial epithelial cells: effectiveness of N-acetylcysteine.

    Science.gov (United States)

    Mata, Manuel; Sarrion, Irene; Armengot, Miguel; Carda, Carmen; Martinez, Isidoro; Melero, Jose A; Cortijo, Julio

    2012-01-01

    Persistent respiratory syncytial virus (RSV) infections have been associated with the exacerbation of chronic inflammatory diseases, including chronic obstructive pulmonary disease (COPD). This virus infects the respiratory epithelium, leading to chronic inflammation, and induces the release of mucins and the loss of cilia activity, two factors that determine mucus clearance and the increase in sputum volume. These alterations involve reactive oxygen species-dependent mechanisms. The antioxidant N-acetylcysteine (NAC) has proven useful in the management of COPD, reducing symptoms, exacerbations, and accelerated lung function decline. NAC inhibits RSV infection and mucin release in human A549 cells. The main objective of this study was to analyze the effects of NAC in modulating ciliary activity, ciliagenesis, and metaplasia in primary normal human bronchial epithelial cell (NHBEC) cultures infected with RSV. Our results indicated that RSV induced ultrastructural abnormalities in axonemal basal bodies and decreased the expression of β-tubulin as well as two genes involved in ciliagenesis, FOXJ1 and DNAI2. These alterations led to a decrease in ciliary activity. Furthermore, RSV induced metaplastic changes to the epithelium and increased the number of goblet cells and the expression of MUC5AC and GOB5. NAC restored the normal functions of the epithelium, inhibiting ICAM1 expression, subsequent RSV infection through mechanisms involving nuclear receptor factor 2, and the expression of heme oxygenase 1, which correlated with the restoration of the antioxidant capacity, the intracellular H(2)O(2) levels and glutathione content of NHBECs. The results presented in this study support the therapeutic use of NAC for the management of chronic respiratory diseases, including COPD.

  5. Perilla frutescens leaf extract inhibits mite major allergen Der p 2-induced gene expression of pro-allergic and pro-inflammatory cytokines in human bronchial epithelial cell BEAS-2B.

    Directory of Open Access Journals (Sweden)

    Jer-Yuh Liu

    Full Text Available Perilla frutescens has been used in traditional medicine for respiratory diseases due to its anti-bacterial and anti-inflammatory activity. This study aimed to investigate effects of Perilla frutescens leaf extract (PFE on expression of pro-allergic and pro-inflammatory cytokines in airway epithelial cells exposed to mite major allergen Der p 2 (DP2 and the underlying mechanisms. Our results showed that PFE up to 100 µg/mL had no cytotoxic effect on human bronchial epithelial cell BEAS-2B. Further investigations revealed that PFE dose-dependently diminished mRNA expression of pro-allergic cytokine IL-4, IL-5, IL-13 and GM-CSF, as well as pro-inflammatory cytokine IL-6, IL-8 and MCP-1 in BEAS-2B cells treated with DP2. In parallel to mRNA, the DP-2-elevated levels of the tested cytokines were decreased. Further investigation showed that DP2-indued phosphorylation of p38 MAPK (P38 and JNK, but not Erk1/2, was also suppressed by PFE. In addition, PFE elevated cytosolic IκBα level and decreased nuclear NF-κB level in DP2-stimulated BEAS-2B cells. Taken together, these findings revealed that PFE significantly diminished both mRNA expression and protein levels of pro-allergic and pro-inflammatory cytokines in response to DP2 through inhibition of P38/JNK and NK-κB activation. These findings suggest that PFE should be beneficial to alleviate both allergic and inflammatory responses on airway epithelium in response to aeroallergens.

  6. Effects of long-term progesterone exposure on porcine uterine gene expression: progesterone alone does not induce secreted phosphoprotein 1 (osteopontin) in glandular epithelium.

    Science.gov (United States)

    Bailey, Daniel W; Dunlap, Kathrin A; Erikson, David W; Patel, Atish K; Bazer, Fuller W; Burghardt, Robert C; Johnson, Greg A

    2010-10-01

    Pigs experience significant conceptus loss near mid-gestation, correlating with increasing glandular epithelial (GE) development and secretory activity. Secreted phosphoprotein 1 (SPP1, osteopontin) increases in GE between days 30 and 40 of pregnancy and is expressed in the GE of day 90 pseudopregnant pigs, suggesting that progesterone (P(4)) from corpora lutea is responsible for induction of SPP1 in GE. In this study, pigs were ovariectomized and treated daily with P(4) to assess effects of 40 days of P(4) exposure on SPP1, P(4) receptor (PGR), uteroferrin (ACP5), and fibroblast growth factor 7 (FGF7) expression in porcine endometria. PGR mRNA decreased in pigs injected with P(4) compared with pigs injected with corn oil (CO), and PGRs were downregulated in the luminal epithelium (LE) and GE. ACP5 mRNA increased in pigs injected with P(4) compared with pigs injected with CO, and ACP5 was induced in the GE of P(4)-treated pigs. FGF7 mRNA increased in pigs injected with P(4) compared with pigs injected with CO, and FGF7 was induced in the LE and GE of P(4)-treated pigs. SPP1 mRNA was not different between pigs injected with P(4) compared with pigs injected with CO, and SPP1 was not present in the GE of P(4)-treated pigs. Therefore, long-term P(4), in the absence of ovarian and/or conceptus factors, does not induce SPP1 expression in GE. We hypothesize that a servomechanism involving sequential effects of multiple hormones and cytokines, similar to those for sheep and humans, is required for GE differentiation and function, including the synthesis and secretion of SPP1.

  7. The Role of the Capase-8 Inhibitor FLIP in Androgen-Withdrawal Induced Death of Prostate Epithelium

    Science.gov (United States)

    2006-01-01

    in apoptosing rat prostate glands. • 1.2 Use immunohistochemistry and in situ hybridization to determine the spatial (cell-type specific) pattern of...FLIP expression in apoptosing rat prostate glands. • 1.3 Measure the levels of FLIP mRNA (by quantitative RT-PCR) and protein (by affinity precipitation...and immunoblotting) in NRP-152 cells induced to apoptose by TGFß. Results: We previously reported having found that FLIP protein levels decline by

  8. The Role of the Caspase-8 Inhibitor FLIP in Androgen-Withdrawal Induced Death of Prostate Epithelium

    Science.gov (United States)

    2007-01-01

    precipitation and immunoblotting to measure FLIP protein levels in apoptosing rat prostate glands. • 1.2 Use immunohistochemistry and in situ hybridization to...determine the spatial (cell-type specific) pattern of FLIP expression in apoptosing rat prostate glands. • 1.3 Measure the levels of FLIP mRNA (by...quantitative RT-PCR) and protein (by affinity precipitation and immunoblotting) in NRP-152 cells induced to apoptose by TGFß. Results: We previously

  9. House dust mite allergen Der f enhanced bronchial epithelial cell cytokine expression

    Institute of Scientific and Technical Information of China (English)

    BAO QING SUN; WEI TANG; ALBERT CHAN; ADRIAN WU; NAN SHAN ZHONG

    2006-01-01

    The house dust mites ( Dermatophagoides farinae, Der f) are the major source of aeroallergens implicated in the expression of atopic disorders, including asthma, allergic rhinitis and atopic dermatitis. In particular, strong circumstantial evidence suggests that house dust mite antigens are important precipitating factors of asthma. Many house dust mite allergens are proteases that can elicit airway inflammation by stimulating the release of cytokines from bronchial epithelial cells. To investigate whether Derf allergen proteases induced cytokine production from the epithelial cell line BEAS-2B,BEAS-2B cells were cultured with 4 different concentrations of Derf (0.02, 0.2, 2, 20 μg/ml) for 24-96 h, after which supernatants were assayed for interleukin (IL)-6 and IL-8 with ELISA. Reverse transcription-PCR was also performed. The cell sheets were intact throughout the observation in control group without any exposure to Derf antigen. In the experimental groups cells treated with Der f allergen showed changes in the anchorage status of the monolayer. There was a significant increase in the level of cytokine production compared with the untreated sample. The release of IL-6 and IL-8 increased in a concentration-dependent manner ( P < 0.05, respectively) with the addition of increasing dosage of Der f to the cell sheets. Levels of IL-6 and IL-8 began to rise at 24 h and 48 h after allergen exposure, and they increased significantly in the supernatants at 72 h and 96 h. At the same time the concentration dependence of induction of IL-6 and IL-8 expression as well as an increase in the expression of IL-6 and IL-8 mRNA manifested evidently. HDM-induced airway inflammation may include Der f-mediated release of inflammatory mediators, and the proteolytic activity of an allergen may stimulate the release of proinflammatory cytokines from human bronchial epithelium. It is suggested that IL-6 and IL-8 production by bronchial epithelial cells may play a role in the

  10. Using Mathematical Modelling to Explore Hypotheses about the Role of Bovine Epithelium Structure in Foot-And-Mouth Disease Virus-Induced Cell Lysis.

    Directory of Open Access Journals (Sweden)

    Kyriaki Giorgakoudi

    Full Text Available Foot-and-mouth disease (FMD is a highly contagious disease of cloven-hoofed animals. FMD virus (FMDV shows a strong tropism for epithelial cells, and FMD is characterised by cell lysis and the development of vesicular lesions in certain epithelial tissues (for example, the tongue. By contrast, other epithelial tissues do not develop lesions, despite being sites of viral replication (for example, the dorsal soft palate. The reasons for this difference are poorly understood, but hypotheses are difficult to test experimentally. In order to identify the factors which drive cell lysis, and consequently determine the development of lesions, we developed a partial differential equation model of FMDV infection in bovine epithelial tissues and used it to explore a range of hypotheses about epithelium structure which could be driving differences in lytic behaviour observed in different tissues. Our results demonstrate that, based on current parameter estimates, epithelial tissue thickness and cell layer structure are unlikely to be determinants of FMDV-induced cell lysis. However, differences in receptor distribution or viral replication amongst cell layers could influence the development of lesions, but only if viral replication rates are much lower than current estimates.

  11. Role of pigment epithelium-derived factor on proliferation and migration of choroidal capillary endothelium induced by vascular endothelial growth factor in vitro

    Institute of Scientific and Technical Information of China (English)

    WANG Feng-hua; SUN Xiao-dong; ZHANG Xi; XU Xun; ZHU Qi; HUANG Jian-nan; FAN Ying; GU Qing; LIU Hai-yang

    2007-01-01

    Background Pigment epithelium-derived factor (PEDF) is expressed in several normal organs and identified as an inhibitor of neovascularization. In the present study, we investigated the effect of PEDF in an in vitro model of ocular choroidal neovascularization.Methods Microdissection was used to isolate the human choroidal endothelial cells (CECs), followed by the use of superparamagnetic beads (Dynabeads) coated with the CD31 antibody, which selectively binds to the endothelial cell surface. The mitogenic and motogenic effects of vascular endothelial growth factor (VEGF) on cultured choroidal capillary endothelial cells were examined in the presence or absence of PEDF (1, 10, 100, and 1000 ng/ml) using cell counts and migration assays.Results Cells bound to the beads were isolated using a magnetic particle concentrator and they were successfully cultured and characterized to be endothelial cells that possessed greater than 95% immunoreactivity to von Willebrand factor. PEDF suppressed the proliferation and migration of VEGF-induced choroidal capillary endothelial cells. However,the concentration of PEDF which we used has little effect on normal CECs.Conclusions PEDF played an important role on the growth and migration of VEGF-stimulated choroidal endothelial cell.These findings suggest that PEDF may be an effective approach to the treatment of choroidal neovascular disorders.

  12. [Rhino-bronchial syndrome].

    Science.gov (United States)

    Gani, F; Vallese, G; Piglia, P; Senna, G; Mezzelani, P; Pozzi, E

    2000-12-01

    A close anatomical and functional relationship between superior and inferior airways is well documented. A typical example is offered by the close relationship between allergic rhinitis and asthma whose close connection is documented by epidemiological and pathological data. The mechanisms which can explain this phenomenon are not fully known but naso-bronchial reflexes, mouth-breathing due to nasal obstruction and aspiration of nasal secretions seem all to be important. Moreover it has been recently proved that the treatment of rhinitis can improve the concomitant asthma thus confirming their relationship. Another less frequent association is between sinusitis and asthma. Such a connection seems to be frequent in patients suffering of atopic rhinitis but also in patients presenting a nasal obstruction of different nature such as deviations of the nasal septum, adenoid hypertrophy etc. Also in this case a correct medical or surgical treatment of sinusitis can improve asthma symptomathology. Finally a classic example of involvement of superior and inferior airways is represented by the syndrome of ASA intolerance. These patients in fact initially complain of rhinitis which afterwards is complicated by the onset of nasal polyposis and asthma which can prove clinically very severe. Nowadays, anyway, there is no evidence that the treatment of rhinitis or polypectomy can improve the clinical course of asthma. In conclusion, diseases of superior and inferior airways must be considered in strict connection and need the same global treatment.

  13. Connective Tissue Growth Factor Expression in Human Bronchial Epithelial Cells

    Institute of Scientific and Technical Information of China (English)

    Amrita DOSANJH

    2006-01-01

    Connective tissue growth factor (CTGF) is a cysteine-rich protein that promotes extracellular matrix deposition. CTGF is selectively induced by transforming growth factor β and des-Arg kallidin in lung fibroblasts and increases steady-state mRNA levels of α type I collagen, 5α-integrin and fibronectin in fibroblasts. Bronchial epithelial cells have been proposed to functionally interact with lung fibroblasts. We therefore investigated if bronchial epithelial cells are able to synthesize CTGF. Human bronchial epithelial cells were grown to subconfluence in standard growth media. Proliferating cells grown in small airway growth media were harvested following starvation for up to 24 h. Expression of CTGF transcripts was measured by PCR. Immunocytochemistry was also completed using a commercially available antibody.The cells expressed readily detectable CTGF transcripts. Starvation of these cells resulted in a quantitative decline of CTGF transcripts. Direct sequencing of the PCR product identified human CTGF. Immunocytochemistry confirmed intracellular CTGF in the cells and none in negative control cells. We conclude that bronchial epithelial cells could be a novel source of CTGF. Bronchial epithelial cell-derived CTGF could thus directly influence the deposition of collagen in certain fibrotic lung diseases.

  14. The accumulations of HIF-1α and HIF-2α by JNK and ERK are involved in biphasic effects induced by different levels of arsenite in human bronchial epithelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Xu, Yuan; Li, Yuan [Institute of Toxicology, School of Public Health, Nanjing Medical University, Nanjing 210029, Jiangsu (China); The Key Laboratory of Modern Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 210029, Jiangsu (China); Li, Huiqiao [Qujing Center for Disease Control and Prevention, Qujing 655000, Yunnan (China); Pang, Ying; Zhao, Yue; Jiang, Rongrong; Shen, Lu [Institute of Toxicology, School of Public Health, Nanjing Medical University, Nanjing 210029, Jiangsu (China); The Key Laboratory of Modern Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 210029, Jiangsu (China); Zhou, Jianwei; Wang, Xinru [The Key Laboratory of Modern Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 210029, Jiangsu (China); Liu, Qizhan, E-mail: drqzliu@hotmail.com [Institute of Toxicology, School of Public Health, Nanjing Medical University, Nanjing 210029, Jiangsu (China); The Key Laboratory of Modern Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 210029, Jiangsu (China)

    2013-01-15

    The biphasic effects of arsenite, in which low levels of arsenite induce cell proliferation and high levels of arsenite induce DNA damage and apoptosis, apparently contribute to arsenite-induced carcinogenesis. However, the mechanisms underlying this phenomenon are not well understood. In this study, we investigated the effects of different levels of arsenite on cell proliferation, DNA damage and apoptosis as well as on signal transduction pathways in human bronchial epithelial (HBE) cells. Our results show that a low level of arsenite activates extracellular signal-regulated kinases (ERK), which probably mediate arsenite-inhibited degradation of ubiquitinated hypoxia-inducible factor-2α (HIF-2α) in HBE cells. ERK inhibition blocks cell proliferation induced by a low level of arsenite, in part via HIF-2α. In contrast, a high level of arsenite activates c-Jun N-terminal kinases (JNK), which provoke a response to suppress ubiquitinated HIF-1α degradation. Down-regulation of HIF-1α by inhibiting JNK, however, increases the DNA damage but decreases the apoptosis induced by a high level of arsenite. Thus, data in the present study suggest that the accumulations of HIF-1α and HIF-2α by JNK and ERK are involved in different levels of arsenite-induced biphasic effects, with low levels of arsenite inducing cell proliferation and high levels of arsenite inducing DNA damage and apoptosis in HBE cells. -- Highlights: ► Biphasic effects induced by different concentrations of arsenite. ► Different regulation of ERK or JNK signal pathway by arsenite. ► Different regulation of HIF1α or HIF 2α by arsenite.

  15. Pulmonary microRNA profiles identify involvement of Creb1 and Sec14l3 in bronchial epithelial changes in allergic asthma

    Science.gov (United States)

    Bartel, Sabine; Schulz, Nikola; Alessandrini, Francesca; Schamberger, Andrea C.; Pagel, Philipp; Theis, Fabian J.; Milger, Katrin; Noessner, Elfriede; Stick, Stephen M.; Kicic, Anthony; Eickelberg, Oliver; Freishtat, Robert J.; Krauss-Etschmann, Susanne

    2017-01-01

    Asthma is highly prevalent, but current therapies cannot influence the chronic course of the disease. It is thus important to understand underlying early molecular events. In this study, we aimed to use microRNAs (miRNAs) - which are critical regulators of signaling cascades - to identify so far uncharacterized asthma pathogenesis pathways. Therefore, deregulation of miRNAs was assessed in whole lungs from mice with ovalbumin (OVA)-induced allergic airway inflammation (AAI). In silico predicted target genes were confirmed in reporter assays and in house-dust-mite (HDM) induced AAI and primary human bronchial epithelial cells (NHBE) cultured at the air-liquid interface. We identified and validated the transcription factor cAMP-responsive element binding protein (Creb1) and its transcriptional co-activators (Crtc1-3) as targets of miR-17, miR-144, and miR-21. Sec14-like 3 (Sec14l3) - a putative target of Creb1 - was down-regulated in both asthma models and in NHBE cells upon IL13 treatment, while it’s expression correlated with ciliated cell development and decreased along with increasing goblet cell metaplasia. Finally, we propose that Creb1/Crtc1-3 and Sec14l3 could be important for early responses of the bronchial epithelium to Th2-stimuli. This study shows that miRNA profiles can be used to identify novel targets that would be overlooked in mRNA based strategies. PMID:28383034

  16. Tiotropium bromide suppresses smoke inhalation and burn injury-induced ERK 1/2 and SMAD 2/3 signaling in sheep bronchial submucosal glands.

    Science.gov (United States)

    Jacob, Sam; Zhu, Yong; Asmussen, Sven; Ito, Hiroshi; Herndon, David N; Enkhbaatar, Perenlei; Hawkins, Hal K; Cox, Robert A

    2014-05-01

    The effects of tiotropium bromide on ERK 1/2, SMAD 2/3 and NFκB signaling in bronchial submucosal gland (SMG) cells of sheep after smoke inhalation and burn injury (S + B) were studied. We hypothesized that tiotropium would modify intracellular signaling processes within SMG cells after injury. Bronchial tissues were obtained from uninjured (sham, n = 6), S + B injured sheep 48 h after injury (n = 6), and injured sheep nebulized with tiotropium (n = 6). The percentage (mean ± SD) of cells showing nuclear localization of phosphorylated ERK 1/2, pSMAD 2/3, and NFκB (p65) was determined by immunohistochemistry. Nuclear pERK 1/2 staining was increased in injured animals as compared to sham, (66 ± 20 versus 14 ± 9), p = 0.0022, as was nuclear pSMAD, 84 ± 10 versus 20 ± 10, p = 0.0022. There was a significant decrease in pERK 1/2 labeling in the tiotropium group compared to the injured group (31 ± 20 versus 66 ± 20, p = 0.013), and also a decrease in pSMAD labeling, 62 ± 17 versus 84 ± 10, p = 0.04. A significant increase for NFκB (p65) was noted in injured animals as compared to sham (73 ± 16 versus 7 ± 6, p = 0.0022). Tiotropium-treated animals showed decreased p65 labeling as compared to injured (35 ± 17 versus 74 ± 16, p = 0.02). The decrease in nuclear expression of pERK, pSMAD and NFκB molecules in SMG cells with tiotropium treatment is suggestive that their activation after injury is mediated in part through muscarinic receptors.

  17. Physiotherapy and bronchial mucus transport

    NARCIS (Netherlands)

    van der Schans, CP; Postma, DS; Koeter, GH; Rubin, BK

    1999-01-01

    Cough and expectoration of mucus are the best-known symptoms in patients with pulmonary disease, The most applied intervention for these symptoms is the use of chest physiotherapy to increase bronchial mucus transport and reduce retention of mucus in the airways, Chest physiotherapy interventions ca

  18. The effect of desalivation on the malignant transformation of the tongue epithelium and associated stromal myofibroblasts in a rat 4-nitroquinoline 1-oxide-induced carcinogenesis model.

    Science.gov (United States)

    Vered, Marilena; Grinstein-Koren, Osnat; Reiter, Shoshana; Allon, Irit; Dayan, Dan

    2010-08-01

    The aim of our study was to analyse desalivated rat tongue epithelium for histopathological changes, proliferating cell nuclear antigen (PCNA), and epithelium-associated stromal myofibroblasts [SMF; alpha-smooth muscle actin (alphaSMA)] following 0.001% 4-nitroquinoline 1-oxide (4NQO) administration in drinking water. Results were compared with those of identically treated but salivated specimens. 4NQO was administered for 7, 14, 22 and 28 weeks. Tongue length was divided into anterior, middle and posterior 'thirds'. The histopathological changes per 'third' were scored as normal epithelium, hyperplasia, dysplasia, carcinoma-in-situ, and superficial and invasive carcinoma. The PCNA and alphaSMA stains were assessed by a point-counting method. At all time points, the histopathological changes in the anterior and middle thirds were higher in the desalivated than in the salivated group (P 0.05). PCNA scores were significantly lower in the desalivated vs. the salivated group at almost all time points and tongue thirds (P tongue epithelium in the early stages. PCNA cannot be regarded as a marker of proliferation and probably contributes to this process by other mechanisms. Emergence of SMF seems to be highly dependent on growth factors from saliva in addition to factors from cancerous cells.

  19. Tumorigenicity studies of induced pluripotent stem cell (iPSC-derived retinal pigment epithelium (RPE for the treatment of age-related macular degeneration.

    Directory of Open Access Journals (Sweden)

    Hoshimi Kanemura

    Full Text Available Basic studies of human pluripotential stem cells have advanced rapidly and stem cell products are now seeing therapeutic applications. However, questions remain regarding the tumorigenic potential of such cells. Here, we report the tumorigenic potential of induced pluripotent stem cell (iPSC-derived retinal pigment epithelium (RPE for the treatment of wet-type, age-related macular degeneration (AMD. First, immunodeficient mouse strains (nude, SCID, NOD-SCID and NOG were tested for HeLa cells' tumor-forming capacity by transplanting various cell doses subcutaneously with or without Matrigel. The 50% Tumor Producing Dose (TPD50 value is the minimal dose of transplanted cells that generated tumors in 50% of animals. For HeLa cells, the TPD50 was the lowest when cells were embedded in Matrigel and transplanted into NOG mice (TPD50 = 10(1.1, n = 75. The TPD50 for undifferentiated iPSCs transplanted subcutaneously to NOG mice in Matrigel was 10(2.12; (n = 30. Based on these experiments, 1×10(6 iPSC-derived RPE were transplanted subcutaneously with Matrigel, and no tumor was found during 15 months of monitoring (n = 65. Next, to model clinical application, we assessed the tumor-forming potential of HeLa cells and iPSC 201B7 cells following subretinal transplantation of nude rats. The TPD50 for iPSCs was 10(4.73 (n = 20 and for HeLa cells 10(1.32 (n = 37 respectively. Next, the tumorigenicity of iPSC-derived RPE was tested in the subretinal space of nude rats by transplanting 0.8-1.5×10(4 iPSC-derived RPE in a collagen-lined (1 mm×1 mm sheet. No tumor was found with iPSC-derived RPE sheets during 6-12 months of monitoring (n = 26. Considering the number of rodents used, the monitoring period, the sensitivity of detecting tumors via subcutaneous and subretinal administration routes and the incidence of tumor formation from the iPSC-derived RPE, we conclude that the tumorigenic potential of the iPSC-derived RPE was

  20. Study of Therapeutic Mechanism of Acupuncture in Treating Bronchial Asthma

    Institute of Scientific and Technical Information of China (English)

    LI; Ji

    2001-01-01

    It has been considered by modern medicine that bronchial asthma is a chronic airway allergic inflammation (AAI) which is the major factor that induces reversible airway ventilating disturbance and bronchial hyper-responsiveness (BHR) in asthmatic patients, as well as a correlation between the delayed-phase onset of asthma and AAI is more significant than immediate-phase onset of asthma in its pathogenesis. Anti-inflammatory therapy as a fundamental principle of treatment for bronchial asthma has been brought forward during the interval phase so that a large number of anti-AAI drugs to significantly enhance the curative effect such as inhalant corticoid, disodium cromoglycate, and leukotriene receptors antagonist, etc., has been rapidly developed. Additionally, traditional Chinese medicine (TCM) and integration of TCM and western medicine (WM) therapies, including acupuncture, are gradually taken into account by the medical circle as a characteristic in our country for treatment of bronchial asthma. It is worthy of being pointed out that the curative effect of acupuncture and moxibustion in treating asthma is evident, and that its therapeutic mechanism has to a certain extent, been found along with the recent deep-going acupunctural research.……

  1. Study of Therapeutic Mechanism of Acupuncture in Treating Bronchial Asthma

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    @@  It has been considered by modern medicine that bronchial asthma is a chronic airway allergic inflammation (AAI) which is the major factor that induces reversible airway ventilating disturbance and bronchial hyper-responsiveness (BHR) in asthmatic patients, as well as a correlation between the delayed-phase onset of asthma and AAI is more significant than immediate-phase onset of asthma in its pathogenesis. Anti-inflammatory therapy as a fundamental principle of treatment for bronchial asthma has been brought forward during the interval phase so that a large number of anti-AAI drugs to significantly enhance the curative effect such as inhalant corticoid, disodium cromoglycate, and leukotriene receptors antagonist, etc., has been rapidly developed. Additionally, traditional Chinese medicine (TCM) and integration of TCM and western medicine (WM) therapies, including acupuncture, are gradually taken into account by the medical circle as a characteristic in our country for treatment of bronchial asthma. It is worthy of being pointed out that the curative effect of acupuncture and moxibustion in treating asthma is evident, and that its therapeutic mechanism has to a certain extent, been found along with the recent deep-going acupunctural research.

  2. Lung Sounds in Bronchial Asthma

    Directory of Open Access Journals (Sweden)

    Yukio Nagasaka

    2012-01-01

    In lung sound analysis, the narrower the airways are, the higher the frequency of breathing sounds is, and, if a patient has higher than normal breathing sounds, i.e., bronchial sounds, he or she may have airway narrowing or airway inflammation. It is sometimes difficult to detect subtle changes in lung sounds; therefore, we anticipate that automated analysis of lung sounds will be used to overcome these difficulties in the near future.

  3. Eosinofilia en esputo versus óxido nítrico en aire exhalado: aplicación clínica en el asma Eosinophils in induced sputum versus nitric oxide in exhaled air: clinical utility in bronchial asthma

    Directory of Open Access Journals (Sweden)

    M.J. Álvarez

    2009-08-01

    Full Text Available Fundamento. La eosinofilia en esputo inducido permite optimizar el tratamiento antiinflamatorio en el asma pero sus requerimientos técnicos hacen poco viable su aplicación clínica. Evaluamos si el óxido nítrico (FE NO, un marcador inflamatorio de fácil medición, podía suplir a la eosinofilia en esputo, así como la relación que ambos índices mostraban con aspectos clínicos y funcionales del asma. Métodos. Se estudiaron 106 asmáticos (50 con tratamiento antiinflamatorio [AB+] y 56 sin él [AB-] y 15 controles. Tras completar un cuestionario clínico, se les realizó medición de FE NO, espirometría forzada e inducción de esputo. Se calculó el valor de pendiente de la curva concentración-respuesta (CCR obtenida tras la inhalación de salino hipertónico. Resultados. Los resultados de FE NO y de eosinofilia en esputo fueron valorables en 100% y 81% de los casos respectivamente. Los valores de FE NO fueron superiores en AB- que en AB+ y en éstos respecto a controles. La eosinofilia, mayor en asmáticos que en controles aunque sin diferencias entre AB+ y AB-, se correlacionó con la FE NO y se comportó de forma paralela a la pendiente CCR. Había correlación entre el nivel de control del asma y los índices inflamatorios (eosinofilia y FE NO en el grupo AB- pero no en el AB+. Conclusión. La obtención de FE NO es rápida, sencilla y da resultados inmediatos que se correlacionan con la actividad del asma. Puede desempeñar un papel relevante en el diagnóstico y manejo terapéutico inicial de asma, aunque se necesitan más estudios para evaluar su aplicación en la monitorización a largo plazo de la enfermedad, por la influencia tan notable que tiene sobre sus niveles el tratamiento antiinflamatorio.Background. Assessment of eosinophils in induced sputum can help to optimize anti-inflammatory therapy in bronchial asthma, but this is a very demanding technique. The aim of the study is to compare nitric oxide in exhaled air (Fe

  4. Treatment of bronchial ruptures by delayed surgery

    Institute of Scientific and Technical Information of China (English)

    1999-01-01

    Objective:To study the causes that resulted in delayed surgery for bronchial ruptures and the results.Methods:The cases with the bronchial ruptures by the delayed surgery last decade were retrospectively reviewed.The causes and unsatisfactory results were analysed.Results:The severe complications usually occurred after the delayed surgery and the results were not as satisfactory as those by early surgery.Conclusion:The bronchial ruptures ought to be operated in the early stage after being wounded.

  5. Airway surface liquid volume expansion induces rapid changes in amiloride-sensitive Na+ transport across upper airway epithelium-Implications concerning the resolution of pulmonary edema

    Science.gov (United States)

    Azizi, Fouad; Arredouani, Abdelilah; Mohammad, Ramzi M

    2015-01-01

    During airway inflammation, airway surface liquid volume (ASLV) expansion may result from the movement of plasma proteins and excess liquid into the airway lumen due to extravasation and elevation of subepithelial hydrostatic pressure. We previously demonstrated that elevation of submucosal hydrostatic pressure increases airway epithelium permeability resulting in ASLV expansion by 500 μL cm−2 h−1. Liquid reabsorption by healthy airway epithelium is regulated by active Na+ transport at a rate of 5 μL cm−2 h−1. Thus, during inflammation the airway epithelium may be submerged by a large volume of luminal liquid. Here, we have investigated the mechanism by which ASLV expansion alters active epithelial Na+ transport, and we have characterized the time course of the change. We used primary cultures of tracheal airway epithelium maintained under air interface (basal ASLV, depth is 7 ± 0.5 μm). To mimic airway flooding, ASLV was expanded to a depth of 5 mm. On switching from basal to expanded ASLV conditions, short-circuit current (Isc, a measure of total transepithelial active ion transport) declined by 90% with a half-time (t1/2) of 1 h. 24 h after the switch, there was no significant change in ATP concentration nor in the number of functional sodium pumps as revealed by [3H]-ouabain binding. However, amiloride-sensitive uptake of 22Na+ was reduced by 70% upon ASLV expansion. This process is reversible since after returning cells back to air interface, Isc recovered with a t1/2 of 5–10 h. These results may have important clinical implications concerning the development of Na+ channels activators and resolution of pulmonary edema. PMID:26333829

  6. Trans, trans-2,4-decadienal, a product found in cooking oil fumes, induces cell proliferation and cytokine production due to reactive oxygen species in human bronchial epithelial cells.

    Science.gov (United States)

    Chang, Louis W; Lo, Wai-Sze; Lin, Pinpin

    2005-10-01

    Dienaldehydes are by-products of peroxidation of polyunsaturated lipids and commonly found in many foods or food-products. Both National Cancer Institute (NCI) and NTP have expressed great concern on the potential genotoxicity and carcinogenicity of dienaldehydes. Trans, trans-2,4-decadienal (tt-DDE or 2,4-De), a specific type of dienaldehyde, is abundant in heated oils and has been associated with lung adenocarcinoma development in women due to their exposure to oil fumes during cooking. Cultured human bronchial epithelial cells (BEAS-2B cells) were exposed to 0.1 or 1.0 microM tt-DDE for 45 days, and oxidative stress, reactive oxygen species (ROS) production, GSH/GSSG ratio, cell proliferation, and expression of TNFalpha and IL-1beta were measured. The results show that tt-DDE induced oxidative stress, an increase in ROS production, and a decrease in GSH/GSSG ratio (glutathione status) in a dose-dependent manner. Treatment of BEAS-2B cells with 1.0 microM tt-DDE for 45 days increased cell proliferation and the expression and release of pro-inflammatory cytokines TNFalpha and IL-1beta. Cotreatment of BEAS-2B cells with antioxidant N-acetylcysteine prevented tt-DDE-induced cell proliferation and release of cytokines. Therefore, these results suggest that tt-DDE-induced changes may be due to increased ROS production and enhanced oxidative stress. Since increased cell proliferation and the release of TNF-alpha and IL-1beta are believed to be involved in tumor promotion, our results suggest that tt-DDE may play a role in cancer promotion. Previous studies on dienaldehydes have focused on their genotoxic or carcinogenic effects in the gastrointestinal tract; the present study suggests a potential new role of tt-DDE as a tumor promoter in human lung epithelial cells.

  7. Imaging diagnosis of bronchial asthma and related diseases

    Energy Technology Data Exchange (ETDEWEB)

    Sakai, Fumikazu; Fujimura, Mikihiko; Kimura, Fumiko; Fujimura, Kaori; Hayano, Toshio; Nishii, Noriko; Machida, Haruhiko; Toda, Jo; Saito, Naoko [Tokyo Women' s Medical Coll. (Japan)

    2002-12-01

    We describe imaging features of bronchial asthma and related diseases. The practical roles of imaging diagnosis are the evaluation of severity and complications of bronchial asthma and differential diagnosis of diseases showing asthmatic symptoms other than bronchial asthma. (author)

  8. [Delayed asthma bronchiale due to epoxy resin].

    Science.gov (United States)

    Authried, Georg; Al-Asadi, Haifaa; Møller, Ulla; Sherson, David Lee

    2013-10-28

    Epoxy resin is a low molecular weight agent, which can cause both acute and delayed allergic reactions. However, it is known causing skin reactions with direct or airborne contact. Rarely it can cause airway reactions like asthma bronchiale. We describe a case of a windmill worker who developed delayed asthma bronchiale due to airborne contact with epoxy resin.

  9. Asbestos exposure increases human bronchial epithelial cell fibrinolytic activity.

    Science.gov (United States)

    Gross, T J; Cobb, S M; Gruenert, D C; Peterson, M W

    1993-03-01

    Chronic exposure to asbestos fibers results in fibrotic lung disease. The distal pulmonary epithelium is an early target of asbestos-mediated injury. Local plasmin activity may be important in modulating endoluminal inflammatory responses in the lung. We studied the effects of asbestos exposure on cell-mediated plasma clot lysis as a marker of pericellular plasminogen activation. Exposing human bronchial epithelial (HBE) cells to 100 micrograms/ml of asbestos fibers for 24 h resulted in increased plasma clot lysis. Fibrinolytic activity was augmented in a dose-dependent fashion, was not due to secreted protease, and occurred only when there was direct contact between the plasma clot and the epithelial monolayer. Further analysis showed that asbestos exposure increased HBE cell-associated urokinase-type plasminogen activator (uPA) activity in a time-dependent manner. The increased cell-associated PA activity could be removed by acid washing. The increase in PA activity following asbestos exposure required new protein synthesis because it was abrogated by treatment with either cycloheximide or actinomycin D. Therefore, asbestos exposure increases epithelial-mediated fibrinolysis by augmenting expression of uPA activity at the cell surface by mechanisms that require new RNA and protein synthesis. These observations suggest a novel mechanism whereby exposure of the distal epithelium to inhaled particulates may result in a chronic inflammatory response that culminates in the development of fibrotic lung disease.

  10. [Epidural emphysema complicating bronchial asthma].

    Science.gov (United States)

    Rouetbi, N; Ben Saad, A; Joobeur, S; Skhiri, N; Cheikh Mhamed, S; Mribah, H; El Kamel, A

    2012-12-01

    Epidural emphysema is an exceptional complication of bronchial asthma, revealed by an incidental finding in chest tomography. We report a case of a 21-year-old man admitted with asthma attack complicated by subcutaneous and mediastinal emphysema. Chest tomography confirmed the mediastinal emphysema and also revealed the epidural emphysema within the vertebral canal. Neurological examination was negative. The patient showed complete recovery 10days after the onset of symptoms. The epidural emphysema is a rare complication during asthma attacks. The benignity of this complication should not require a systematic chest tomography.

  11. "Bronchial Artery Delivery of Viral Vectors for Gene delivery in Cystic Fibrosis; Superior to Airway Delivery?"

    Directory of Open Access Journals (Sweden)

    Coutelle Charles C

    2002-04-01

    Full Text Available Abstract Background Attempts at gene therapy for the pulmonary manifestations of Cystic Fibrosis have relied mainly on airway delivery. However the efficiency of gene transfer and expression in the airway epithelia has not reached therapeutic levels. Access to epithelial cells is not homogenous for a number of reasons and the submucosal glands cannot be reached via the airways. Presentation We propose to inject gene delivery vectors directly into bronchial arteries combined with pre-delivery of vascular endothelial growth factor to increase vascular endothelial permeability and post-delivery flow reduction by balloon occlusion. Thus it may be possible to reach mucous secreting cells of the bronchial luminal epithelium and the submucosal glands in an increased and homogenous fashion. Testing This combination of techniques to the best of our knowledge has not previously been investigated, and may enable us to overcome some of the current limitations to gene therapy for Cystic Fibrosis.

  12. Alternative spliced CD1d transcripts in human bronchial epithelial cells.

    Directory of Open Access Journals (Sweden)

    Kambez Hajipouran Benam

    Full Text Available CD1d is a MHC I like molecule which presents glycolipid to natural killer T (NKT cells, a group of cells with diverse but critical immune regulatory functions in the immune system. These cells are required for optimal defence against bacterial, viral, protozoan, and fungal infections, and control of immune-pathology and autoimmune diseases. CD1d is expressed on antigen presenting cells but also found on some non-haematopoietic cells. However, it has not been observed on bronchial epithelium, a site of active host defence in the lungs. Here, we identify for the first time, CD1D mRNA variants and CD1d protein expression on human bronchial epithelial cells, describe six alternatively spliced transcripts of this gene in these cells; and show that these variants are specific to epithelial cells. These findings provide the basis for investigations into a role for CD1d in lung mucosal immunity.

  13. Cigarette smoke and the terminal ileum: increased autophagy in murine follicle-associated epithelium and Peyer's patches.

    Science.gov (United States)

    Verschuere, Stephanie; Allais, Liesbeth; Bracke, Ken R; Lippens, Saskia; De Smet, Rebecca; Vandenabeele, Peter; Brusselle, Guy G G; Cuvelier, Claude A

    2012-03-01

    Cigarette smoke (CS) exposure is associated with increased autophagy in several cell types, such as bronchial epithelial cells. Smoking is also an environmental risk factor in Crohn's disease, in which impairment of the autophagy-mediated anti-bacterial pathway has been implicated. So far, it is unknown whether CS induces autophagy in the gut. Here, we examined the effect of chronic CS exposure on autophagy in the follicle-associated epithelium (FAE) of murine Peyer's patches. Transmission electron microscopy revealed that the proportion of cell area occupied by autophagic vesicles significantly increased in the FAE after CS exposure. An increased number of autophagic vesicles was observed in the FAE, whereas the vesicle size remained unaltered. Besides enterocytes, also M-cells contain more autophagic vesicles upon CS exposure. In addition, the mRNA level of the autophagy-related protein Atg7 in the underlying Peyer's patches is increased after CS exposure, which indicates that the autophagy-inducing effect of CS is not limited to the FAE. In conclusion, our results demonstrate that CS exposure induces autophagy in murine FAE and in the underlying immune cells of Peyer's patches, suggesting that CS exposure increases the risk for Crohn's disease by causing epithelial oxidative damage, which needs to be repaired by autophagy.

  14. 真菌引起支气管哮喘发展和加重的免疫学机制%Immune mechanism of the development and exacerbation of bronchial asthma induced by fungi

    Institute of Scientific and Technical Information of China (English)

    王林林; 时国朝

    2011-01-01

    Bronchial asthma (asthma) is an inflammatory disease of the airways which maybe worsened due to many extrinsic factors.The most common trigger is the infection of fungi.There is increasing evidence for the presence of fungal sensitization in asthmatics.There is also a strong association between fungal sensitization and severity of asthma.Many studies mainly elucidated the immune mechanism of severe asthma induced by fungi from two aspects in recent years.One is immune cells,the other epithelial cells.The elucidation of the associated of mechanism is significant to explore the new approaches of asthma treatment.%支气管哮喘(简称哮喘)是常见的气道慢性炎症性疾病,多种环境因素可引起哮喘恶化加重,其中真菌感染是一个很重要的因素.有很多证据显示哮喘患者存在真菌致敏,且在真菌致敏和哮喘严重度之间存在强的相关性.近年来很多研究主要从真菌对免疫细胞和上皮细胞的影响两个方面阐释了真菌引起哮喘加重的免疫学机制.此免疫学机制的阐明对于探索治疗重症哮喘的新途径有重要的意义.

  15. Assessing dysplasia of a bronchial biopsy with FTIR spectroscopic imaging

    Science.gov (United States)

    Foreman, Liberty; Kimber, James A.; Oliver, Katherine V.; Brown, James M.; Janes, Samuel M.; Fearn, Tom; Kazarian, Sergei G.; Rich, Peter

    2015-03-01

    An FTIR image of an 8 µm section of de-paraffinised bronchial biopsy that shows a histological transition from normal to severe dysplasia/squamous cell carcinoma (SCC) in situ was obtained in transmission by stitching together images of 256 x 256 µm recorded using a 96 x 96 element FPA detector. Each pixel spectrum was calculated from 128 co-added interferograms at 4 cm-1 resolution. In order to improve the signal to noise ratio, blocks of 4x4 adjacent pixels were subsequently averaged. Analyses of this spectral image, after conversion of the spectra to their second derivatives, show that the epithelium and the lamina propria tissue types can be distinguished using the area of troughs at either 1591, 1334, 1275 or 1215 cm-1 or, more effectively, by separation into two groups by hierarchical clustering (HCA) of the 1614-1465 region. Due to an insufficient signal to noise ratio, disease stages within the image could not be distinguished with this extent of pixel averaging. However, after separation of the cell types, disease stages within either the epithelium or the lamina propria could be distinguished if spectra were averaged from larger, manually selected areas of the tissue. Both cell types reveal spectral differences that follow a transition from normal to cancerous histology. For example, spectral changes that occurred in the epithelium over the transition from normal to carcinoma in situ could be seen in the 1200-1000 cm-1 region, particularly as a decrease in the second derivative troughs at 1074 and 1036 cm-1 , consistent with changes in some form of carbohydrate. Spectral differences that indicate a disease transition from normal to carcinoma in the lamina propria could be seen in the 1350-1175 cm-1 and 1125-1030 cm-1 regions. Thus demonstrating that a progression from healthy to severe dysplasia/squamous cell carcinoma (SCC) in situ can be seen using FTIR spectroscopic imaging and multivariate analysis.

  16. Stimulation of mucin secretion from human bronchial epithelial cells by mast cell chymase

    Institute of Scientific and Technical Information of China (English)

    Shao-heng HE; Jian ZHENG

    2004-01-01

    AIM: To investigate the effect ofchymase on the mucin secretion from human bronchial epithelial cells. METHODS:Primarily-cultured human bronchial epithelial (PCHBE) cells and normal human bronchial epithelial (NHBE) cells were cultured with chymase or other stimulus in a mixture of bronchial epithelial growth medium (BEGM) and Dulbecco's modified Eagle's medium (DMEM), and the quantities of stimulatory mucin release were recorded.MUC5AC mucin was measured with an ELISA and dolichos biflorus agglutinin (DBA) mucin was determined with an enzyme linked DBA assay. RESULTS: A dose-dependent secretion of DBA mucin from PCHBE cells was observed with chymase with a maximum secretion of 98 % above baseline being achieved following 3 h incubation.The action of chymase started from 1 h, peaked at 3 h and dramatically decreased at 20 h following incubation.Chymase was able to also stimulate approximately 38 % increase in MUC5AC mucin release from PCHBE cells, and about 121% increase in DBA mucin release from NHBE cells. A chymase inhibitor soybean trypsin inhibitor (SBTI)was able to inhibit up to 85 % chymase induced mucin release, indicating that the enzymatic activity was essential for the actions of chymase on bronchial epithelial cells. CONCLUSION: Chymase is a potent stimulus of mucin secretion from human bronchial epithelial cells. It can contribute to mucus hypersecretion process in the patients with chronic obstructive pulmonary disease or asthma.

  17. Effect of TRPV1 gene mutation on bronchial asthma in children before and after treatment.

    Science.gov (United States)

    Chen, Chuan-Liang; Li, Hong; Xing, Xiao-Hong; Guan, Hai-Shan; Zhang, Jian-Hua; Zhao, Jun-Wu

    2015-01-01

    Bronchial asthma is a worldwide disease with high incidence. It not only harms children's physical and mental health, but it also brings a heavy burden to their families as well as the society. However, the trigger and pathogenesis of the disease remain unclear. This study aimed to analyze TRPV1 gene mutation and expression of cytokines in children with acute bronchial asthma before and after treatment, thus providing theoretical guidance for the diagnosis and treatment of bronchial asthma in children. Real-time quantitative polymerase chain reaction was adopted to detect TRPV1 mRNA expression level and enzyme-linked immuno sorbent assay was used to detect the serum total IgE level, eosinophil (EOS) number, IL-4, IL-5, and interferon (IFN) gamma levels in peripheral venous blood of children in the healthy control group and asthma group before and after treatment. Logistic regression analysis was applied to analyze the most essential factor inducing bronchial asthma in children. TRPV1 mRNA level of peripheral blood in the asthma group was higher than that in the control group before treatment (p asthma in children. TRPV1 gene mutation was closely related to bronchial asthma in children, which provided a theoretical basis for the treatment and prognosis of children with bronchial asthma.

  18. Environmental risk factors and allergic bronchial asthma.

    Science.gov (United States)

    D'Amato, G; Liccardi, G; D'Amato, M; Holgate, S

    2005-09-01

    The prevalence of allergic respiratory diseases such as bronchial asthma has increased in recent years, especially in industrialized countries. A change in the genetic predisposition is an unlikely cause of the increase in allergic diseases because genetic changes in a population require several generations. Consequently, this increase may be explained by changes in environmental factors, including indoor and outdoor air pollution. Over the past two decades, there has been increasing interest in studies of air pollution and its effects on human health. Although the role played by outdoor pollutants in allergic sensitization of the airways has yet to be clarified, a body of evidence suggests that urbanization, with its high levels of vehicle emissions, and a westernized lifestyle are linked to the rising frequency of respiratory allergic diseases observed in most industrialized countries, and there is considerable evidence that asthmatic persons are at increased risk of developing asthma exacerbations with exposure to ozone, nitrogen dioxide, sulphur dioxide and inhalable particulate matter. However, it is not easy to evaluate the impact of air pollution on the timing of asthma exacerbations and on the prevalence of asthma in general. As concentrations of airborne allergens and air pollutants are frequently increased contemporaneously, an enhanced IgE-mediated response to aeroallergens and enhanced airway inflammation could account for the increasing frequency of allergic respiratory allergy and bronchial asthma. Pollinosis is frequently used to study the interrelationship between air pollution and respiratory allergy. Climatic factors (temperature, wind speed, humidity, thunderstorms, etc) can affect both components (biological and chemical) of this interaction. By attaching to the surface of pollen grains and of plant-derived particles of paucimicronic size, pollutants could modify not only the morphology of these antigen-carrying agents but also their allergenic

  19. Role of acetylcholine and muscarinic receptors in serotonin-induced bronchoconstriction in the mouse.

    Science.gov (United States)

    Kummer, Wolfgang; Wiegand, Silke; Akinci, Sibel; Schinkel, Alfred H; Wess, Jürgen; Koepsell, Hermann; Haberberger, Rainer Viktor; Lips, Katrin Susanne

    2006-01-01

    For the murine trachea, it has been reported that constriction evoked by serotonin (5-HT) is largely dependent on acetylcholine (ACh) released from the epithelium, owing to the sensitivity of the 5-HT response to epithelium removal, sensitivity to atropine, and insensitivity to tetrodotoxin (Moffatt et al., 2003). Consistent with this assumption, the respiratory epithelium contains ACh, its synthesizing enzyme, and the high-affinity choline transporter CHT1 (Reinheimer et al., 1996; Pfeil et al., 2003; Proskocil et al., 2004). Recently, we demonstrated that ACh can be released from non-neuronal cells by corticosteroid-sensitive polyspecific organic cation transporters (OCTs), which are also expressed by airway epithelial cells (Lips et al., 2005). Hence, we proposed that 5-HT evokes release of ACh from epithelial cells via OCTs and that this epithelial-derived ACh induces bronchoconstriction. We tested this hypothesis in a well-established model of videomorphometric analysis of bronchial diameter in precision-cut murine lung slices utilizing epithelium removal to assess the role of the epithelium, OCT mouse knockout (KO) strains to assess the role of OCT isoforms, and muscarinic receptor M2/M3 double-KO mice to assess the cholinergic component of 5-HT induced bronchoconstriction, as bronchi of this strain are entirely unresponsive to cholinergic stimulation(Struckmann et al., 2003).

  20. Mechanically patterning the embryonic airway epithelium

    Science.gov (United States)

    Varner, Victor D.; Gleghorn, Jason P.; Miller, Erin; Radisky, Derek C.; Nelson, Celeste M.

    2015-01-01

    Collections of cells must be patterned spatially during embryonic development to generate the intricate architectures of mature tissues. In several cases, including the formation of the branched airways of the lung, reciprocal signaling between an epithelium and its surrounding mesenchyme helps generate these spatial patterns. Several molecular signals are thought to interact via reaction-diffusion kinetics to create distinct biochemical patterns, which act as molecular precursors to actual, physical patterns of biological structure and function. Here, however, we show that purely physical mechanisms can drive spatial patterning within embryonic epithelia. Specifically, we find that a growth-induced physical instability defines the relative locations of branches within the developing murine airway epithelium in the absence of mesenchyme. The dominant wavelength of this instability determines the branching pattern and is controlled by epithelial growth rates. These data suggest that physical mechanisms can create the biological patterns that underlie tissue morphogenesis in the embryo. PMID:26170292

  1. Pulmonary infections in swine induce altered porcine surfactant protein D expression and localization to dendritic cells in bronchial-associated lymphoid tissue

    DEFF Research Database (Denmark)

    Sørensen, C.M.; Holmskov, U.; Aalbæk, B.;

    2005-01-01

    Surfactant protein D (SP-D) is a pattern-recognition molecule of the innate immune system that recognizes various microbial surface-specific carbohydrate and lipid patterns. In vitro data has suggested that this binding may lead to increased microbial association with macrophages and dendritic...... among pSP-D, pathogens, phagocytic cells and dendritic cells. Lung tissue was collected from experimental and natural bronchopneumonias caused by Actinobacillus pleuropneumoniae or Staphylococcus aureus, and from embolic and diffuse interstitial pneumonia, caused by Staph. aureus or Arcanobacterium......SP-D through the specialized M cells overlying (BALT). In conclusion, we have shown that pSP-D expression in the lung surfactant is induced by bacterial infection by an aerogenous route rather than by a haematogenous route, and that the protein interacts specifically with alveolar macrophages...

  2. Autocrine Acetylcholine, Induced by IL-17A via NFκB and ERK1/2 Pathway Activation, Promotes MUC5AC and IL-8 Synthesis in Bronchial Epithelial Cells

    Directory of Open Access Journals (Sweden)

    Angela Marina Montalbano

    2016-01-01

    Full Text Available IL-17A is overexpressed in the lung during acute neutrophilic inflammation. Acetylcholine (ACh increases IL-8 and Muc5AC production in airway epithelial cells. We aimed to characterize the involvement of nonneuronal components of cholinergic system on IL-8 and Muc5AC production in bronchial epithelial cells stimulated with IL-17A. Bronchial epithelial cells were stimulated with recombinant human IL-17A (rhIL-17A to evaluate the ChAT expression, the ACh binding and production, the IL-8 release, and the Muc5AC production. Furthermore, the effectiveness of PD098,059 (inhibitor of MAPKK activation, Bay11-7082 (inhibitor of IkBα phosphorylation, Hemicholinium-3 (HCh-3 (choline uptake blocker, and Tiotropium bromide (Spiriva® (anticholinergic drug was tested in our in vitro model. We showed that rhIL-17A increased the expression of ChAT, the levels of ACh binding and production, and the IL-8 and Muc5AC production in stimulated bronchial epithelial cells compared with untreated cells. The pretreatment of the cells with PD098,059 and Bay11-7082 decreased the ChAT expression and the ACh production/binding, while HCh-3 and Tiotropium decreased the IL-8 and Muc5AC synthesis in bronchial epithelial cells stimulated with rhIL-17A. IL-17A is involved in the IL-8 and Muc5AC production promoting, via NFκB and ERK1/2 pathway activation, the synthesis of ChAT, and the related activity of autocrine ACh in bronchial epithelial cells.

  3. 克菌丹诱导人支气管上皮细胞转化%Transformation of Human Bronchial Epithelial Cells Induced by Captan

    Institute of Scientific and Technical Information of China (English)

    许建宁; 董琳; 王全凯; 胡洁; 李学峰

    2011-01-01

    [Methods] 16HBE cell was treated with captan at the concentration from 0.0625 to 1.0 mg/L and observed biological characteristics to ensure whether cell malignant transformation occurred. [Results] The 30th generation of 16HBE treated with captan grew faster, while its sensibility to conA and ability of growing in semi-solid agar also increased. The morphological change of transformed cells could be founded under scanning electron microscope and the pathology suggested that tumor formed in nude mice was squamous cell carcinoma. [Conclusions] Captan could induce 16HBE cell to get malignant transformation. This transformation model would be the foundation for further studying and evaluating the health damage caused by captan.%[方法]16HBE细胞经0.0625~1.0 mg/L剂量的克菌丹染毒,通过观察染毒细胞形态及恶性表型鉴定,检测克菌丹诱导16HBE细胞的转化.[结果]克菌丹转化第30代细胞生长速度增快,对conA凝集敏感性增强,失去贴壁生长依赖性,电镜下可见明显的形态学改变,裸鼠体内形成肿块为鳞状上皮细胞癌.[结论]克菌丹可直接诱导16HBE细胞发生恶性转化,该模型的建立为克菌丹对健康损伤效应研究及其评价奠定了基础.

  4. Permanent Cortical Blindness After Bronchial Artery Embolization

    Energy Technology Data Exchange (ETDEWEB)

    Doorn, Colette S. van, E-mail: cvandoorn@gmail.com; De Boo, Diederick W., E-mail: d.w.deboo@amc.uva.nl [Academic Medical Centre, Department of Radiology (Netherlands); Weersink, Els J. M., E-mail: e.j.m.weersink@amc.uva.nl [Academic Medical Centre, Department of Pulmonology (Netherlands); Delden, Otto M. van, E-mail: o.m.vandelden@amc.uva.nl; Reekers, Jim A., E-mail: j.a.reekers@amc.uva.nl; Lienden, Krijn P. van, E-mail: k.p.vanlienden@amc.uva.nl [Academic Medical Centre, Department of Radiology (Netherlands)

    2013-12-15

    A 35-year-old female with a known medical history of cystic fibrosis was admitted to our institution for massive hemoptysis. CTA depicted a hypertrophied bronchial artery to the right upper lobe and showed signs of recent bleeding at that location. Bronchial artery embolization (BAE) was performed with gelfoam slurry, because pronounced shunting to the pulmonary artery was present. Immediately after BAE, the patient developed bilateral cortical blindness. Control angiography showed an initially not opacified anastomosis between the embolized bronchial artery and the right subclavian artery, near to the origin of the right vertebral artery. Cessation of outflow in the bronchial circulation reversed the flow through the anastomosis and allowed for spill of embolization material into the posterior circulation. Unfortunately the cortical blindness presented was permanent.

  5. Permanent cortical blindness after bronchial artery embolization.

    Science.gov (United States)

    van Doorn, Colette S; De Boo, Diederick W; Weersink, Els J M; van Delden, Otto M; Reekers, Jim A; van Lienden, Krijn P

    2013-12-01

    A 35-year-old female with a known medical history of cystic fibrosis was admitted to our institution for massive hemoptysis. CTA depicted a hypertrophied bronchial artery to the right upper lobe and showed signs of recent bleeding at that location. Bronchial artery embolization (BAE) was performed with gelfoam slurry, because pronounced shunting to the pulmonary artery was present. Immediately after BAE, the patient developed bilateral cortical blindness. Control angiography showed an initially not opacified anastomosis between the embolized bronchial artery and the right subclavian artery, near to the origin of the right vertebral artery. Cessation of outflow in the bronchial circulation reversed the flow through the anastomosis and allowed for spill of embolization material into the posterior circulation. Unfortunately the cortical blindness presented was permanent.

  6. Acute and chronic respiratory lesions induced by sulfur mustard in guinea pigs: Role of tachykinins

    Energy Technology Data Exchange (ETDEWEB)

    Calvet, J.H.; Trouiller, G.; Harf, A.

    1993-05-13

    We investigated in anesthetized guinea pigs the involvement of tachykinins in respiratory alterations after an airway intoxication by sulfur mustard (SM). Early lesions were evaluated after 5h. Respiratory system resistance (R) and compliance were measured by the occlusion method and airway microvascular permeability by measuring the Evans Blue dye concentration in the trachea and main bronchi. Two groups of animals were studied treated with capsaicin (which induces a tachykinin depletion) or by its vehicle. Capsaicin pretreatment had no effect on the measured parameters. We also measured 14 J after the intoxication tracheal epithelium neutral endopeptidase (NEP) (the main enzyme which degrades tachykinins). In addition bronchial responsiveness to exogenous substance P was studied in two groups of animals intoxicated with SM or not. Tracheal epithelium NEP activity was decreased from 0.448 + or 0.027 nmol.min- 1.mg protein- 1 in controls to 0. 182 + or 0.038 in intoxicated animals. Response to substance P was greater in intoxicated animals with R=2.98 + or - 1.57 cmH20.MI-1.s versus 0.35 + or 0.02 in controls, after 5.10-5 M aerosolized substance P These results suggest tachykinins are not preponderant in the early stage lesions but that bronchial hyperactivity is present at recovery, related to epithelium NEP depletion.

  7. Macrophages are required for dendritic cell uptake of respiratory syncytial virus from an infected epithelium.

    Science.gov (United States)

    Ugonna, Kelechi; Bingle, Colin D; Plant, Karen; Wilson, Kirsty; Everard, Mark L

    2014-01-01

    We have previously shown that the respiratory syncytial virus [RSV] can productively infect monocyte derived dendritic cells [MoDC] and remain dormant within the same cells for prolonged periods. It is therefore possible that infected dendritic cells act as a reservoir within the airways of individuals between annual epidemics. In the present study we explored the possibility that sub-epithelial DCs can be infected with RSV from differentiated bronchial epithelium and that in turn RSV from DCs can infect the epithelium. A dual co-culture model was established in which a differentiated primary airway epithelium on an Air Liquid Interface (ALI) was cultured on a transwell insert and MoDCs were subsequently added to the basolateral membrane of the insert. Further experiments were undertaken using a triple co-culture model in which in which macrophages were added to the apical surface of the differentiated epithelium. A modified RSV [rr-RSV] expressing a red fluorescent protein marker of replication was used to infect either the MoDCs or the differentiated epithelium and infection of the reciprocal cell type was assessed using confocal microscopy. Our data shows that primary epithelium became infected when rr-RSV infected MoDCs were introduced onto the basal surface of the transwell insert. MoDCs located beneath the epithelium did not become infected with virus from infected epithelial cells in the dual co-culture model. However when macrophages were present on the apical surface of the primary epithelium infection of the basal MoDCs occurred. Our data suggests that RSV infected dendritic cells readily transmit infection to epithelial cells even when they are located beneath the basal layer. However macrophages appear to be necessary for the transmission of infection from epithelial cells to basal dendritic cells.

  8. VATS right upper lobe bronchial sleeve resection

    Science.gov (United States)

    Ma, Qianli

    2016-01-01

    Background The aim of this study is to discuss video-assisted thoracic surgery (VATS) sleeve bronchial lobectomy when handling the locally advanced central lung cancer (involving the trachea and/or main bronchus). Methods A 2.5 cm × 1.0 cm mass was found in the right upper lobe. Bronchoscopy demonstrated the tumor obstructing the right upper lobe bronchus and involved the right main bronchus and bronchus intermedius. Interrupted sutures were chosen for bronchial anastomosis. Bronchial membrane was sutured first, and then circumference end-to-end anastomoses were carried out using 3-0 absorbable sutures. Results There were no complications and the patient was discharged 8 days postoperatively. Conclusions The third intercostal space of the anterior axillary line was suggested for right upper lobe bronchial sleeve resection. This incision can reduce the distance and angle between the anastomosis to the incision, and facilitate anastomosis. This approach can also prevent operator from fatigue for keeping one posture for a long time. Clearance of the mediastinal lymph nodes before cutting the bronchus was helpful for exposing the right main bronchus, the upper lobe bronchus and bronchus intermedius satisfied. And this option would avoid pulling bronchial anastomosis during mediastinal lymph nodes clearance. Interrupted suture was safe and effective for VATS bronchial anastomosis. PMID:27621889

  9. Effect of acupuncture on bronchial asthma.

    Science.gov (United States)

    Yu, D Y; Lee, S P

    1976-11-01

    1. Needle acupuncture was performed at three sites in twenty patients in a clinical attack of bronchial asthma. 2. In all patients the symptoms of bronchoconstriction improved during the attacks when the correct site was stimulated, and in five patients wheezing was abolished. 3. Stimulation at the correct site produced a significant increase in the mean FEV1-0 (58%) and FVC (29%) but not in maximal mid-expiratory flow rate (MMFR; 76%), when compared with the findings before acupuncture, along with a significant fall in the Pa,CO2 and an insignificant fall in Pa,O2. A mild tachycardia was also observed. 4. After acupuncture a greater improvement in FEV1-0, FVC and MMFR was produced by inhalation of isoprenaline. 5. No significant changes in FEV1-0, FVC, MMFR, pulse rate or arterial blood gas tensions occurred after acupuncture at control sites. 6. In four of the patients during clinical remission acupuncture was performed before and after histamine aerosol challenge, but there was no effect on either the severity or the duration of the histamine-induced bronchoconstriction. 7. It is concluded that acupunture probably reduced the reflex component of the bronchoconstriction, but failed to influence direct smooth muscle constriction caused by histamine.

  10. AKT1E¹⁷K Is Oncogenic in Mouse Lung and Cooperates with Chemical Carcinogens in Inducing Lung Cancer.

    Directory of Open Access Journals (Sweden)

    Donatella Malanga

    Full Text Available The hotspot AKT1E17K mutation in the pleckstrin homology domain of AKT1 occurs in approximately 0.6-2% of human lung cancers. Recently, we have demonstrated that AKT1E17K transforms immortalized human bronchial cells. Here by use of a transgenic Cre-inducible murine strain in the wild type Rosa26 (R26 locus (R26-AKT1E17K mice we demonstrate that AKT1E17K is a bona-fide oncogene and plays a role in the development of lung cancer in vivo. In fact, we report that mutant AKT1E17K induces bronchial and/or bronchiolar hyperplastic lesions in murine lung epithelium, which progress to frank carcinoma at very low frequency, and accelerates tumor formation induced by chemical carcinogens. In conclusion, AKT1E17K induces hyperplasia of mouse lung epithelium in vivo and cooperates with urethane to induce the fully malignant phenotype.

  11. AKT1E17K Is Oncogenic in Mouse Lung and Cooperates with Chemical Carcinogens in Inducing Lung Cancer

    Science.gov (United States)

    Malanga, Donatella; Belmonte, Stefania; Colelli, Fabiana; Scarfò, Marzia; De Marco, Carmela; Oliveira, Duarte Mendes; Mirante, Teresa; Camastra, Caterina; Gagliardi, Monica; Rizzuto, Antonia; Mignogna, Chiara; Paciello, Orlando; Papparella, Serenella; Fagman, Henrik; Viglietto, Giuseppe

    2016-01-01

    The hotspot AKT1E17K mutation in the pleckstrin homology domain of AKT1 occurs in approximately 0.6–2% of human lung cancers. Recently, we have demonstrated that AKT1E17K transforms immortalized human bronchial cells. Here by use of a transgenic Cre-inducible murine strain in the wild type Rosa26 (R26) locus (R26-AKT1E17K mice) we demonstrate that AKT1E17K is a bona-fide oncogene and plays a role in the development of lung cancer in vivo. In fact, we report that mutant AKT1E17K induces bronchial and/or bronchiolar hyperplastic lesions in murine lung epithelium, which progress to frank carcinoma at very low frequency, and accelerates tumor formation induced by chemical carcinogens. In conclusion, AKT1E17K induces hyperplasia of mouse lung epithelium in vivo and cooperates with urethane to induce the fully malignant phenotype. PMID:26859676

  12. Experimental Study on Lung Cancer Model Induced by Bronchial Perfusion of 3, 4-benzopyrene in Pigs%3,4-苯并芘支气管灌注构建猪肺癌模型的实验研究

    Institute of Scientific and Technical Information of China (English)

    陈锦润; 杨立民; 张震; 王维; 赵珍

    2013-01-01

    目的:探讨3,4-苯并芘经气管导管支气管灌注构建猪肺癌模型的可行性.方法购置24头实验猪,随机分为模型组、对照组,每组12头.实验猪麻醉满意后行气管插管,经气管导管向模型组支气管内注入3,4-苯并芘-玉米油混合液,对照组注入等量玉米油.每周灌注1次,连续16周.于第16周、32周、48周对全部实验猪行肺部CT扫描,观察肺部有无病灶.第48周解剖实验猪肺、食管、胃肠道、肝及脑等脏器,观察有无肿瘤形成,并对肿块及实验猪的肺组织切片进行苏木素伊红( hematoxylin and eosin, HE)染色分析.结果对照组肺部CT及解剖均未发现肺部肿瘤.模型组中,8头肺部CT显示有不同部位、大小不等的占位性病变,病理学均证实为恶性肿瘤,其中3头中分化腺癌,2头高分化鳞癌,1头肺泡细胞癌,2头腺鳞癌.4头肺部CT无异常,其中一头食管距声门2 cm处有一2 cm×1.5 cm×1.0 cm肿块,标本送病理检查证实为食管磷癌.另外3头及对照组肺部CT及解剖均未发现肿瘤.模型组实验猪1 a内成功诱发恶性肿瘤,总成瘤率75%,肺部成瘤率为66.66%.结论经气管导管支气管内灌注3,4-苯并芘是一种简便、安全可靠的肺癌动物模型的构建方法.%Objective To investigate the feasibility of pig lung cancer model induced by bronchial perfusion of 3,4-benzopyrene. Methods 24 experimental pig were randomly divided into model group and control group, each containing 12 cases. Experimental pigs were under the anaesthetic state, pigs in the model group were given endobronchial infusion of 3,4 - benzopyrene - corn oil mixture, pigs in control group were injected with equal capacity of corn oil.Perfusion 1 times a week for 16 weeks.In week 16,32 and 48,all experimental pig were given lung CT scans, then the lung lesions were observed.After 48 weeks, the pig lung, esophagus, and gastrointestinal tract

  13. [Research advances in association between pediatric obesity and bronchial asthma].

    Science.gov (United States)

    Zhu, Lian; Xu, Zhi-Liang; Cheng, Yan-Yang

    2016-07-01

    This review article introduces the research advances in the pathophysiological mechanism of obesity in inducing pediatric bronchial asthma, including the role of leptin in obesity and asthma, the association of plasminogen activator inhibitor-1 with obesity and asthma, the association of adiponectin and interleukins with obesity and asthma, and the influence of neurotransmitter on asthma. In particular, this article introduces the latest research on the inhibition of allergic asthma through targeting at the nociceptor of dorsal root ganglion and blocking the signaling pathway of the nociceptor.

  14. Risk factors inducing children bronchial asthma in Bao'an District of Shenzhen City%深圳市宝安区儿童支气管哮喘发病的危险因素

    Institute of Scientific and Technical Information of China (English)

    刘晓娟; 吴智娟; 钟文明

    2013-01-01

    [Objective] To learn the risk factors of bronchial asthma of children in Baoan District of Shenzhen City,and provide basis for early intervening and treating bronchial asthma.[Methods] With case-control study method,a total of 108 cases of children bronchial asthma as case group and 110 cases of non-bronchial asthma as control group.These cases were investigated with self-designed questionnaire,then used single factor analysis and multiple factors analysis method to screen the risk factors.[Results] The study results showed that the risk factors of children bronchial asthma included hypersensitiveness history (OR =2.646),family asthma history (OR =5.155),repeated respiratory infection history (OR =4.116),smoking history of parents (OR =3.028),bad habitation environment (OR =2.123),contacting allergens (OR =4.509),but usually airing quilt (OR =O.500) was the protective factor.[Conclusion] Children bronchial asthma is closely related with hereditary factors,host factors and environmental factors,so it is very important to prevent and intervene children bronchial asthma with high risk factors.%目的 了解深圳市宝安区儿童支气管哮喘(哮喘)发病的危险因素,为早期预防和治疗提供依据.方法 采用病例对照的研究方法,将确诊的108例儿童哮喘病例作为病例组,同时收集110例非支气管哮喘患儿作为对照组;对病例组和对照组进行问卷调查,采用单因素和多因素分析研究儿童哮喘发病的危险因素.结果 研究结果显示,患儿过敏史(OR=2.646)、父母哮喘史(OR=5.155)、呼吸道反复感染史(OR =4.116)、父母吸烟史(OR=3.028)、居住环境差(OR =2.123)、接触过敏原(OR =4.509)为危险因素,而经常晾晒被辱(OR=0.500)为保护因素.结论 儿童支气管哮喘发病与遗传因素、宿主因素、环境因素等密切相关,应针对高危因素和高危人群进行重点预防和干预.

  15. Influenza enhances caspase-1 in bronchial epithelial cells from asthmatic volunteers and is associated with pathogenesis

    Science.gov (United States)

    Background: The leading cause of asthma exacerbation is respiratory viral infection. Innate antiviral defense pathways are altered in the asthmatic epithelium, yet involvement of inflammasome signaling in virus-induced asthma exacerbation is not known. Objective: This study com...

  16. [Bronchial asthma pathogenesis and genetic prognosis development].

    Science.gov (United States)

    Balmasova, I P; Sepiashvili, R I; Sepiashvili, Ia R; Malova, E S

    2014-01-01

    The review is dedicated to an actual problem--genetic prognosis of risk of bronchial asthma development that is quite a complex aspect of studies from a methodological viewpoint. Bronchial asthma--heterogeneous disease by both etiology and clinical characteristics. At the same time genetic prognosis is based on the unity of pathogenetic mechanisms of development, though in immunological reactions that are the base of this disease, alternative variants are possible. The aim of this review is carrying out parallels between modern achievements in the field of deciphering trigger mechanisms of bronchial asthma pathogenesis and object of genetic studies based on these mechanisms. Among the examined conceptions--role of epithelial tissue in trigger mechanisms of bronchial asthma, variants of key role of immune system cells, first of all, T-helpers of various types for further development of inflammatory-effector reactions with damage characteristic for this disease. Compliance of contemporary approaches of genetic studies and novel concepts of bronchial asthma pathogenesis is shown.

  17. The response of human nasal and bronchial organotypic tissue cultures to repeated whole cigarette smoke exposure.

    Science.gov (United States)

    Talikka, Marja; Kostadinova, Radina; Xiang, Yang; Mathis, Carole; Sewer, Alain; Majeed, Shoaib; Kuehn, Diana; Frentzel, Stefan; Merg, Celine; Geertz, Marcel; Martin, Florian; Ivanov, Nikolai V; Peitsch, Manuel C; Hoeng, Julia

    2014-01-01

    Exposure to cigarette smoke (CS) is linked to the development of respiratory diseases, and there is a need to understand the mechanisms whereby CS causes damage. Although animal models have provided valuable insights into smoking-related respiratory tract damage, modern toxicity testing calls for reliable in vitro models as alternatives for animal experimentation. We report on a repeated whole mainstream CS exposure of nasal and bronchial organotypic tissue cultures that mimic the morphological, physiological, and molecular attributes of the human respiratory tract. Despite the similar cellular staining and cytokine secretion in both tissue types, the transcriptomic analyses in the context of biological network models identified similar and diverse biological processes that were impacted by CS-exposed nasal and bronchial cultures. Our results demonstrate that nasal and bronchial tissue cultures are appropriate in vitro models for the assessment of CS-induced adverse effects in the respiratory system and promising alternative to animal experimentation.

  18. Single-Cell RNA Sequencing of the Bronchial Epithelium in Smokers With Lung Cancer

    Science.gov (United States)

    2015-07-01

    14-1-0234 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Jennifer Beane-Ebel, Joshua Campbell , Grant Duclos 5d. PROJECT NUMBER 5e. TASK NUMBER E...cell biology as well as contribute to molecular biology and bioinformatics methods. An example of a broad impact would be if the study suggests...Foundation, NIH/NIAID, Industry award, Internal funds     Name:   Joshua Campbell   Project Role:   Postdoctoral Fellow   Researcher

  19. Single-Cell RNA Sequencing of the Bronchial Epithelium in Smokers With Lung Cancer

    Science.gov (United States)

    2016-07-01

    addition, we spike-in ERCC controls into each well and compare the number of reads aligned to these controls to their known concentrations. A high...each donor, single Hoechst 33342+ PI- CD235a- cells are sorted into five 96-well PCR plates (480 cells), frozen on dry ice and stored at -80 °C until...capacities11. Frozen 96-well PCR plates containing sorted cells are thawed on ice and RNA is directly reverse transcribed (Ambion AM1751) from whole

  20. Human neutrophil defensins and secretory leukocyte proteinase inhibitor in squamous metaplastic epithelium of bronchial airways.

    NARCIS (Netherlands)

    Aarbiou, J.; Schadewijk, A. van; Stolk, J.; Sont, J.K.; Boer, W.I.; Rabe, K.F.; Krieken, J.H.J.M. van; Mauad, T.; Hiemstra, P.S.

    2004-01-01

    OBJECTIVE: The aim of this study was to analyze a possible contribution of human neutrophil defensins and secretory leukocyte proteinase inhibitor (SLPI) to the induction of airway epithelial changes such as squamous cell metaplasia. MATERIALS AND METHODS: The presence of these molecules and the num

  1. Mechanisms underlying epithelium-dependent relaxation in rat bronchioles

    DEFF Research Database (Denmark)

    Kroigaard, Christel; Dalsgaard, Thomas; Simonsen, Ulf

    2010-01-01

    This study investigated the mechanisms underlying epithelium-derived hyperpolarizing factor (EpDHF)-type relaxation in rat bronchioles. Immunohistochemistry was performed, and rat bronchioles and pulmonary arteries were mounted in microvascular myographs for functional studies. An opener of small...... (SK(Ca)) and intermediate (IK(Ca))-conductance calcium-activated potassium channels, NS309 (6,7-dichloro-1H-indole-2,3-dione 3-oxime) was used to induce EpDHF-type relaxation. IK(Ca) and SK(Ca)3 positive immunoreactions were observed mainly in the epithelium and endothelium of bronchioles and arteries......, respectively. In 5-hydroxytryptamine (1 microM)-contracted bronchioles (828 +/- 20 microm, n = 84) and U46619 (0.03 microM)-contracted arteries (720 +/- 24 microm, n = 68), NS309 (0.001-10 microM) induced concentration-dependent relaxations that were reduced by epithelium/endothelium removal and by blocking IK...

  2. Detection of trisomy 7 in bronchial cells from uranium miners

    Energy Technology Data Exchange (ETDEWEB)

    Lechner, J.F.; Neft, R.E.; Belinsky, S.A. [and others

    1995-12-01

    New Mexico was the largest producer of uranium in the western world during 1960s and 1970s. Investigators at the University of New Mexico School of Medicine`s Epidemiology and Cancer Control Program have been conducting epidemiological studies on uranium miners over the past 2 decades. Currently, this cohort includes more than 3600 men who had completed at least 1 y of underground work experience in New Mexico by December 31, 1976. These miners, who are now in their 5th through 7th decades, the age when lung cancer incidence is highest, are at high risk for developing this disease because they were exposed to high levels of radon progeny in the mines, and they also smoked tobacco. However, not all people comparably exposed develop lung cancer; in fact, the lifetime risk of lung cancer for the smoking uranium miners has been projected by epidemiological analyses to be no higher than 50%. Therefore, the identification of gene alterations in bronchial epithelium would be a valuable tool to ascertain which miners are at greatest risk for lung cancer. The underlying significance of the current effort confirms the hypothesis that chronic exposure to high concentrations of {alpha}-particles and tobacco smoke produces genetically altered lung epithelial cells throughout the respiratory tract of some susceptible individuals before they develop clinical disease.

  3. An antagonist of the platelet-activating factor receptor inhibits adherence of both nontypeable Haemophilus influenzae and Streptococcus pneumoniae to cultured human bronchial epithelial cells exposed to cigarette smoke

    Directory of Open Access Journals (Sweden)

    Shukla SD

    2016-07-01

    Full Text Available Shakti D Shukla,1,* Rory L Fairbairn,1,* David A Gell,1 Roger D Latham,1 Sukhwinder S Sohal,1,2 Eugene H Walters,1 Ronan F O’Toole11Breathe Well Centre, School of Medicine, Faculty of Health, University of Tasmania, Hobart, TAS, Australia; 2School of Health Sciences, Faculty of Health, University of Tasmania, Launceston, TAS, Australia*These authors contributed equally to this workBackground: COPD is emerging as the third largest cause of human mortality worldwide after heart disease and stroke. Tobacco smoking, the primary risk factor for the development of COPD, induces increased expression of platelet-activating factor receptor (PAFr in the lung epithelium. Nontypeable Haemophilus influenzae (NTHi and Streptococcus pneumoniae adhere to PAFr on the luminal surface of human respiratory tract epithelial cells.Objective: To investigate PAFr as a potential drug target for the prevention of infections caused by the main bacterial drivers of acute exacerbations in COPD patients, NTHi and S. pneumoniae.Methods: Human bronchial epithelial BEAS-2B cells were exposed to cigarette smoke extract (CSE. PAFr expression levels were determined using immunocytochemistry and quantitative polymerase chain reaction. The epithelial cells were challenged with either NTHi or S. pneumoniae labeled with fluorescein isothiocyanate, and bacterial adhesion was measured using immunofluorescence. The effect of a well-evaluated antagonist of PAFr, WEB-2086, on binding of the bacterial pathogens to BEAS-2B cells was then assessed. In silico studies of the tertiary structure of PAFr and the binding pocket for PAF and its antagonist WEB-2086 were undertaken.Results: PAFr expression by bronchial epithelial cells was upregulated by CSE, and significantly associated with increased bacterial adhesion. WEB-2086 reduced the epithelial adhesion by both NTHi and S. pneumoniae to levels observed for non-CSE-exposed cells. Furthermore, it was nontoxic toward the bronchial epithelial

  4. Bis-Retinoid A2E Induces an Increase of Basic Fibroblast Growth Factor via Inhibition of Extracellular Signal-Regulated Kinases 1/2 Pathway in Retinal Pigment Epithelium Cells and Facilitates Phagocytosis

    Science.gov (United States)

    Balmer, Delphine; Bapst-Wicht, Linda; Pyakurel, Aswin; Emery, Martine; Nanchen, Natacha; Bochet, Christian G.; Roduit, Raphael

    2017-01-01

    Age-related macular degeneration (ARMD) is the leading cause of vision loss in developed countries. Hallmarks of the disease are well known; indeed, this pathology is characterized by lipofuscin accumulation, is principally composed of lipid-containing residues of lysosomal digestion. The N-retinyl-N-retinylidene ethanolamine (A2E) retinoid which is thought to be a cytotoxic component for RPE is the best-characterized component of lipofuscin so far. Even if no direct correlation between A2E spatial distribution and lipofuscin fluorescence has been established in aged human RPE, modified forms or metabolites of A2E could be involved in ARMD pathology. Mitogen-activated protein kinase (MAPK) pathways have been involved in many pathologies, but not in ARMD. Therefore, we wanted to analyze the effects of A2E on MAPKs in polarized ARPE19 and isolated mouse RPE cells. We showed that long-term exposure of polarized ARPE19 cells to low A2E dose induces a strong decrease of the extracellular signal-regulated kinases' (ERK1/2) activity. In addition, we showed that A2E, via ERK1/2 decrease, induces a significant decrease of the retinal pigment epithelium-specific protein 65 kDa (RPE65) expression in ARPE19 cells and isolated mouse RPE. In the meantime, we showed that the decrease of ERK1/2 activity mediates an increase of basic fibroblast growth factor (bFGF) mRNA expression and secretion that induces an increase in phagocytosis via a paracrine effect. We suggest that the accumulation of deposits coming from outer segments (OS) could be explained by both an increase of bFGF-induced phagocytosis and by the decrease of clearance by A2E. The bFGF angiogenic protein may therefore be an attractive target to treat ARMD. PMID:28298893

  5. Upper respiratory tract disease and bronchial asthma

    Institute of Scientific and Technical Information of China (English)

    1993-01-01

    930904 A clinical study on determination ofplasma vasoactive intestinal peptide and its rela-tionship with bronchial responsiveness in asth-matics.LIU Ao(刘翱),et al.Dept Respir Med,Kunming General Hosp,Kunming Command,Kunming,650032.Chin J Intern Med 1993;32(3):165-166.Vasoactive intestinal peptide(VIP),which islocalized in normal human lung,may play an im-portant role in regulating bronchial tone,pul-monary blood flow and mucus secretion.Thelevel of plasma VIP and bronchial responsivenesswere studied in patients with asthma,and chronicbronchitis and in the healthy subjects.The re-sults showed that the level of plasma VIP in

  6. Chronic Pulmonary Aspergillosis Complicating Bronchial Atresia

    Directory of Open Access Journals (Sweden)

    Mazen O. Al-Qadi

    2014-01-01

    Full Text Available Bronchial atresia is a rare pulmonary developmental anomaly characterized by the presence of a focal obliteration of a segmental or lobar bronchial lumen. The lung distal to the atretic bronchus is typically emphysematous along with the presence of mucus filled ectatic bronchi (mucoceles. BA is usually asymptomatic but pulmonary infections can rarely develop in the emphysematous lung distal to the atretic bronchus. We present a unique case of chronic pulmonary aspergillosis (CPA in a patient with BA with no evidence of immune dysfunction. The patient was treated initially with voriconazole and subsequently underwent surgical excision of the involved area. On follow-up, she has done extremely well with no evidence for recurrence. In summary, we describe the first case of chronic pulmonary aspergillosis in an immunocompetent patient with bronchial atresia.

  7. Change of bronchial hyperresponsiveness in asthmatic children

    Directory of Open Access Journals (Sweden)

    Stojković-Anđelković Anđelka

    2011-01-01

    Full Text Available Introduction. Bronchial hyperresponsiveness (BHR is a factor in predicting bronchial asthma independently of inflammation markers. Objective. The aims were to determine the frequency and important predictive facts of BHR and the effect of prophylaxis by Global Initiative for Asthma (GINA and National Asthma Education and Prevention Program (NAEPP on BHR in asthmatic children. Methods. BHR in 106 children was evaluated by the bronchoprovocation test with methacholine. Results. The prevalence rate of symptomatic BHR is 18% for crucial point of PC20=4.1±3.03 mg/ml and PD20=3.22±2.59 μmol methacholine. On average asthmatic children express moderate BHR, which persists even two years after administering prophylaxis. After two years bronchial reactivity is significantly smaller, the change of FEV1 is significantly smaller, the velocity of change of slope dose response curve (sDRC is faster and the provocative concentration of methacholine that causes wheezing is 2-3 times lower. A mild sDRC shows milder bronchoconstriction after two years. The fast change of bronchial reactivity in 41% of asthmatic children is contributed to aero-pollution with sulfur dioxide and/ or, possible insufficient and/or inadequate treatment during two years of administering prophylaxis. A simultaneous effect of allergens from home environment and grass and tree pollens and of excessive aero-pollution on children’s airways is important in the onset of symptomatic BHR. After two years of treatment by GINA and NAEPP children do not show asthma symptoms or show mild asthma symptoms, however bronchial sensitivity remains unchanged. Conclusion. Optimal duration of anti-inflammatory treatment in asthmatic children who show moderate bronchial hyperresponsiveness should be longer than two years.

  8. The impact of allergic rhinitis and asthma on human nasal and bronchial epithelial gene expression.

    Directory of Open Access Journals (Sweden)

    Ariane H Wagener

    Full Text Available BACKGROUND: The link between upper and lower airways in patients with both asthma and allergic rhinitis is still poorly understood. As the biological complexity of these disorders can be captured by gene expression profiling we hypothesized that the clinical expression of rhinitis and/or asthma is related to differential gene expression between upper and lower airways epithelium. OBJECTIVE: Defining gene expression profiles of primary nasal and bronchial epithelial cells from the same individuals and examining the impact of allergic rhinitis with and without concomitant allergic asthma on expression profiles. METHODS: This cross-sectional study included 18 subjects (6 allergic asthma and allergic rhinitis; 6 allergic rhinitis; 6 healthy controls. The estimated false discovery rate comparing 6 subjects per group was approximately 5%. RNA was extracted from isolated and cultured epithelial cells from bronchial brushings and nasal biopsies, and analyzed by microarray (Affymetrix U133+ PM Genechip Array. Data were analysed using R and Bioconductor Limma package. For gene ontology GeneSpring GX12 was used. RESULTS: The study was successfully completed by 17 subjects (6 allergic asthma and allergic rhinitis; 5 allergic rhinitis; 6 healthy controls. Using correction for multiple testing, 1988 genes were differentially expressed between healthy lower and upper airway epithelium, whereas in allergic rhinitis with or without asthma this was only 40 and 301 genes, respectively. Genes influenced by allergic rhinitis with or without asthma were linked to lung development, remodeling, regulation of peptidases and normal epithelial barrier functions. CONCLUSIONS: Differences in epithelial gene expression between the upper and lower airway epithelium, as observed in healthy subjects, largely disappear in patients with allergic rhinitis with or without asthma, whilst new differences emerge. The present data identify several pathways and genes that might be

  9. Effects of nitrogen dioxide on the expression of intercellular adhesion molecule-1, neutrophil adhesion, and cytotoxicity: studies in human bronchial epithelial cells.

    Science.gov (United States)

    Ayyagari, Vijayalakshmi N; Januszkiewicz, Adolph; Nath, Jayasree

    2007-02-01

    Nitrogen Dioxide (NO2) is a product of high-temperature combustion and an environmental oxidant of concern. We have recently reported that early changes in NO2-exposed human bronchial epithelial cells are causally linked to increased generation of proinflammatory mediators, such as nitric oxide/nitrite and cytokines like interleukin (IL)-1beta, tumor necrosis factor (TNF)-alpha and IL-8. The objective of the present in vitro study was to further delineate the cellular mechanisms of NO2-mediated toxicity, and to define the nature of cell death that ensues upon exposure of normal human bronchial epithelial (NHBE) cells to a brief high dose of NO2. Our results demonstrate that the NHBE cells undergo apoptotic cell death during the early post-NO2 period, but this is independent of any significant increase in caspase-3 activity. However, necrotic cell death was more prevalent at later time intervals. Interestingly, an increased expression of HO-1, a redox-sensitive stress protein, was observed in NO2-exposed NHBE cells at 24 h. Since neutrophils (PMNs) play an active role in acute lung inflammation and resultant oxidative injury, we also investigated changes in human PMN-NHBE cell interactions. As compared to normal cells, increased adhesion of PMNs to NO2-exposed cells was observed, which resulted in an increased NHBE cell death. The latter was also increased in the presence of IL-8 and TNF-alpha + interferon (IFN)-gamma, which correlated with upregulation of intercellular adhesion molecule-1 (ICAM-1). Our results confirmed an involvement of nitric oxide (NO) in NO2-induced cytotoxicity. By using NO synthase inhibitors such as L-NAME and 3-aminoguanidine (AG), a significant decrease in cell death, PMN adhesion, and ICAM-1 expression was observed. These findings indicate a role for the L-arginine/NO synthase pathway in the observed NO2-mediated toxicity in NHBE cells. Therapeutic strategies aimed at controlling excess generation of NO and/or inflammatory cytokines may

  10. Induction of mucin secretion from human bronchial tissue and epithelial cells by rhinovirus and lipopolysaccharide

    Institute of Scientific and Technical Information of China (English)

    Shao-heng HE; Jian ZHENG; Ming-ke DUAN

    2004-01-01

    AIM: To examine the effects of rhinovirus and lipopolysaccharide (LPS) on mucin secretion from bronchial tissue and epithelial cells in vitro. METHODS: Human small bronchial tissue fragments (HSBTF) and human bronchial epithelial cells (HBEC) were cultured with rhinovirus 16 and LPS, respectively and culture supernatants were collected for mucin measurement. To determine mucin levels in the culture supernatants, a MUC5AC enzyme linked immunosorbent assay and an enzyme linked lectin assay procedure with dolichos bifiorus agglutinin (DBA)were developed, and mucin release was expressed as percentage increased (or decreased) secretion over baseline level. RESULTS: A concentration-dependent release of DBA mucin and MUC5AC mucin were observed when HSBTF were infected with various concentrations of rhinovirus 16 at 37 ℃. The maximum-induced DBA mucin and MUC5AC mucin release were approximately 258 % and 83 % over baseline. The response of HSBTF to rhinovirus was completely abolished by metabolic inhibitors. Rhinovirus was also able to induce a concentrationdependent release of DBA mucin and MUC5AC mucin from primarily cultured HBEC. LPS 100 mg/L was able to provoke up to approximately 19 % and 54 % increase in DBA and MUC5AC mucin release over baseline, respectively from HSBTF, and 3.1% and 57 % increase from HBEC at 20 h. Soybean trypsin inhibitor (SBTI) 30 mg/L was able to inhibit LPS-induced mucin release from HSBTF and HBEC. CONCLUSION: Rhinovirus is able to induce mucin secretion from human bronchial tissue and bronchial epithelial cells in vitro. LPS can induce MUC5AC mucin release from HSBTF and HBEC.

  11. 支气管哮喘患儿不同治疗方法内皮素和降钙素基因相关肽结果比较%Study of endothelin and calcitonin gene-related peptide levels in children with bronchial asthma by different therapies

    Institute of Scientific and Technical Information of China (English)

    吕汉文; 卢远达; 徐淑兰; 叶彩丽; 林灿华; 周翔

    2002-01-01

    Background: Bronchial asthma is an allergic pulmonary disease. The attack is mostly induced by the inhalation of or contact with allergens, such as pollens, dusts, insects (such as mite), germs, etc. During the attack, patients have severe dyspnea which is due to spasm of bronchial smooth muscles, swelling of the bronchial mucosa, and hypersecretion of the mucus, leading to bronchial obstruction. To observe the endothelin(ET) and calcitonin gene related peptide(CGRP) changes in treating children with bronchial asthma by dopamine( DP), dobutamine( DOB),and regitine.

  12. The effect of inhaled sodium cromoglycate on cellular infiltration into the bronchial mucosa and the expression of adhesion molecules in asthmatics.

    Science.gov (United States)

    Hoshino, M; Nakamura, Y

    1997-04-01

    There is no direct evidence of the anti-inflammatory effect of inhaled sodium cromoglycate (SCG). To investigate whether inhaled SCG has any effect on cellular infiltration into the bronchial mucosa and the expression of adhesion molecules in patients with asthma, biopsies of the bronchial mucosa were taken from nine patients with atopic bronchial asthma before and after treatment with inhaled SCG (8 mg x day(-1)) from a metered-dose inhaler (MDI). Eosinophils were stained with anti-EG2, neutrophils with anti-NP57, mast cells with anti-AA1, T-lymphocytes with anti-CD4, CD8 and CD3, and macrophages with anti-CD68. Intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), endothelial leucocyte adhesion molecule-1 (ELAM-1) and P-selectin were stained at the same time as adhesion molecules expressed in vascular endothelium. The intensity of ICAM-1 expression in the bronchial epithelium was also evaluated. The numbers of eosinophils, mast cells, T-lymphocytes and macrophages were significantly reduced as a result of SCG administration, and the expression of ICAM-1, VCAM-1 and ELAM-1 was also significantly inhibited. A significant correlation was found between ICAM-1 expression and T-lymphocytes and between VCAM-1 expression and eosinophils. It was concluded that sodium cromoglycate does have an effect on the infiltration of the bronchial mucosa by inflammatory cells and also on the expression of adhesion molecules.

  13. Gastrin-releasing peptide receptor expression in non-cancerous bronchial epithelia is associated with lung cancer: a case-control study

    Directory of Open Access Journals (Sweden)

    Egloff Ann Marie

    2012-02-01

    Full Text Available Abstract Background Normal bronchial tissue expression of GRPR, which encodes the gastrin-releasing peptide receptor, has been previously reported by us to be associated with lung cancer risk in 78 subjects, especially in females. We sought to define the contribution of GRPR expression in bronchial epithelia to lung cancer risk in a larger case-control study where adjustments could be made for tobacco exposure and sex. Methods We evaluated GRPR mRNA levels in histologically normal bronchial epithelial cells from 224 lung cancer patients and 107 surgical cancer-free controls. Associations with lung cancer were tested using logistic regression models. Results Bronchial GRPR expression was significantly associated with lung cancer (OR = 4.76; 95% CI = 2.32-9.77 in a multivariable logistic regression (MLR model adjusted for age, sex, smoking status and pulmonary function. MLR analysis stratified by smoking status indicated that ORs were higher in never and former smokers (OR = 7.74; 95% CI = 2.96-20.25 compared to active smokers (OR = 1.69; 95% CI = 0.46-6.33. GRPR expression did not differ by subject sex, and lung cancer risk associated with GRPR expression was not modified by sex. Conclusions GRPR expression in non-cancerous bronchial epithelium was significantly associated with the presence of lung cancer in never and former smokers. The association in never and former smokers was found in males and females. Association with lung cancer did not differ by sex in any smoking group.

  14. Bronchial gland duct ectasia in fatal bronchial asthma: association with interstitial emphysema.

    OpenAIRE

    Cluroe, A.; Holloway, L.; Thomson, K.; Purdie, G; Beasley, R.

    1989-01-01

    To determine the incidence of bronchial gland duct ectasia in fatal asthma and its association with interstitial emphysema, the histological features of 72 patients in whom death was considered to be due to asthma, and 72 matched control subjects in whom sudden death was not attributed to asthma, were reviewed. In all cases and controls, sections of two or more blocks of lung tissue stained with haematoxylin and eosin were obtained at necropsy. Bronchial gland duct ectasia was diagnosed if th...

  15. Directional secretory response of double stranded RNA-induced thymic stromal lymphopoetin (TSLP and CCL11/eotaxin-1 in human asthmatic airways.

    Directory of Open Access Journals (Sweden)

    Gustavo Nino

    Full Text Available BACKGROUND: Thymic stromal lymphoproetin (TSLP is a cytokine secreted by the airway epithelium in response to respiratory viruses and it is known to promote allergic Th2 responses in asthma. This study investigated whether virally-induced secretion of TSLP is directional in nature (apical vs. basolateral and/or if there are TSLP-mediated effects occurring at both sides of the bronchial epithelial barrier in the asthmatic state. METHODS: Primary human bronchial epithelial cells (HBEC from control (n = 3 and asthmatic (n = 3 donors were differentiated into polarized respiratory tract epithelium under air-liquid interface (ALI conditions and treated apically with dsRNA (viral surrogate or TSLP. Sub-epithelial effects of TSLP were examined in human airway smooth muscle cells (HASMC from normal (n = 3 and asthmatic (n = 3 donors. Clinical experiments examined nasal airway secretions obtained from asthmatic children during naturally occurring rhinovirus-induced exacerbations (n = 20 vs. non-asthmatic uninfected controls (n = 20. Protein levels of TSLP, CCL11/eotaxin-1, CCL17/TARC, CCL22/MDC, TNF-α and CXCL8 were determined with a multiplex magnetic bead assay. RESULTS: Our data demonstrate that: 1 Asthmatic HBEC exhibit an exaggerated apical, but not basal, secretion of TSLP after dsRNA exposure; 2 TSLP exposure induces unidirectional (apical secretion of CCL11/eotaxin-1 in asthmatic HBEC and enhanced CCL11/eotaxin-1 secretion in asthmatic HASMC; 3 Rhinovirus-induced asthma exacerbations in children are associated with in vivo airway secretion of TSLP and CCL11/eotaxin-1. CONCLUSIONS: There are virally-induced TSLP-driven secretory immune responses at both sides of the bronchial epithelial barrier characterized by enhanced CCL11/eotaxin-1 secretion in asthmatic airways. These results suggest a new model of TSLP-mediated eosinophilic responses in the asthmatic airway during viral-induced exacerbations.

  16. Bronchial hyperresponsiveness and anti-asthmatic therapy

    NARCIS (Netherlands)

    Kraan, Jan

    1990-01-01

    Many asthmatic patients experience shortness of breath or wheezing, when exposed to cold air, or irritants like baking fumes, exhaust gases or cigarette smoke. This clinical phenomenon has been called bronchial hypemsponsiveness (BHR), which is defined as an exaggerated broncho-obstructive response

  17. Clavicular osteoma associated with bronchial osteomas

    Energy Technology Data Exchange (ETDEWEB)

    Saglik, Yener; Yiliz, H. Yusuf; Erakar, Aziz [Department of Orthopaedic Surgery, Ankara University School of Medicine, 06100, Ankara (Turkey); Kendi, Tuba Karaguelle [Integra MR Imaging Center, Ankara (Turkey); CMRR, University of Minnesota, 2021 6th Street SE, MN 55455, Minneapolis (United States); Guengoer, Adem [Department of Chest Surgery, Ankara University School of Medicine, 06100, Ankara (Turkey); Erekul, Selim [Department of Pathology, Ankara University School of Medicine, 06100, Ankara (Turkey)

    2004-04-01

    Osteoma is a rare benign tumor, composed of bony tissues. It predominantly involves the skull but rarely the long bones. In this report we present a case of clavicular osteoma associated with bronchial osteomas. This association has not previously been reported. There was no evidence of Gardner's syndrome. (orig.)

  18. Pocket epithelium in the pathological setting for HMGB1 release.

    Science.gov (United States)

    Ebe, N; Hara-Yokoyama, M; Iwasaki, K; Iseki, S; Okuhara, S; Podyma-Inoue, K A; Terasawa, K; Watanabe, A; Akizuki, T; Watanabe, H; Yanagishita, M; Izumi, Y

    2011-02-01

    High-mobility group box-1 (HMGB1) protein acts as a transcription factor in the nucleus and also as a pro-inflammatory cytokine when released into extracellular fluids. The presence of higher levels of HMGB1 is reported in the gingival crevicular fluid from periodontal patients. Since the proliferation of bacteria within the periodontal pocket is closely involved in the exacerbation of periodontal disease, it is hypothesized that the periodontal pocket causes the release of HMGB1. Immunohistochemical staining of inflamed gingiva revealed that HMGB1 is exclusively dislocated from the nucleus to the cytoplasm in the pocket epithelium, whereas it is mainly present in the nucleus in the gingival epithelium. Butyric acid, an extracellular metabolite from periodontopathic bacteria populating the periodontal pocket, induced the passive release of HMGB1 as a result of eliciting necrosis in the human gingival epithelial cell line. Thus, the periodontal epithelium may provide a unique pathological setting for HMGB1 release by bacterial insult.

  19. Anti-apoptotic effects of Z alpha1-antitrypsin in human bronchial epithelial cells.

    LENUS (Irish Health Repository)

    Greene, C M

    2010-05-01

    alpha(1)-antitrypsin (alpha(1)-AT) deficiency is a genetic disease which manifests as early-onset emphysema or liver disease. Although the majority of alpha(1)-AT is produced by the liver, it is also produced by bronchial epithelial cells, amongst others, in the lung. Herein, we investigate the effects of mutant Z alpha(1)-AT (ZAAT) expression on apoptosis in a human bronchial epithelial cell line (16HBE14o-) and delineate the mechanisms involved. Control, M variant alpha(1)-AT (MAAT)- or ZAAT-expressing cells were assessed for apoptosis, caspase-3 activity, cell viability, phosphorylation of Bad, nuclear factor (NF)-kappaB activation and induced expression of a selection of pro- and anti-apoptotic genes. Expression of ZAAT in 16HBE14o- cells, like MAAT, inhibited basal and agonist-induced apoptosis. ZAAT expression also inhibited caspase-3 activity by 57% compared with control cells (p = 0.05) and was a more potent inhibitor than MAAT. Whilst ZAAT had no effect on the activity of Bad, its expression activated NF-kappaB-dependent gene expression above control or MAAT-expressing cells. In 16HBE14o- cells but not HEK293 cells, ZAAT upregulated expression of cIAP-1, an upstream regulator of NF-kappaB. cIAP1 expression was increased in ZAAT versus MAAT bronchial biopsies. The data suggest a novel mechanism by which ZAAT may promote human bronchial epithelial cell survival.

  20. Lung function and bronchial reactivity in farmers.

    Science.gov (United States)

    Iversen, M; Dahl, R; Jensen, E J; Korsgaard, J; Hallas, T

    1989-01-01

    The purpose of this study was to evaluate the prevalence and type of lung function disorders in Danish farmers. Three samples of farmers were drawn from a group of unselected farmers who had participated in an epidemiological study. Group I (47 persons) was a sample of the 8% of all farmers who had reported that they had asthma; group II (63 persons) was a sample of the 28% of farmers who had had wheezing, shortness of breath, or cough without phlegm; and group III (34 persons) a sample of the farmers (64% of the total) who had no asthma and no respiratory symptoms. The farmers with symptoms (groups I and II) had low mean levels of FEV1 and high values for residual volume, whereas the symptomless farmers had normal lung function and no airways obstruction. The proportion of farmers with an FEV1 below the 95% confidence limit for predicted values was 43% in group I and 23% in group II; there were none in group III. Bronchial hyperreactivity to histamine occurred in 96% of asthmatic farmers, 67% of farmers with wheezing or shortness of breath, and 59% of symptomless farmers. A low level of FEV1 was associated with the number of years in pig farming and bronchial hyperreactivity in group II but not group I or III. Most of the bronchial hyperreactivity was explained in the multiple regression analysis by a low FEV1, though this was significant only for farmers in group II. Thus farmers who reported asthma, wheezing, shortness of breath, or a dry cough in general had airways obstruction with an increased residual volume, whereas symptomless farmers had normal lung function. Severe bronchial hyperreactivity was mostly explained by a diagnosis of asthma and poor lung function, though some farmers with normal lung function and no respiratory symptoms had increased bronchial reactivity. PMID:2799744

  1. Monitoring asthma in childhood: lung function, bronchial responsiveness and inflammation

    Directory of Open Access Journals (Sweden)

    Alexander Moeller

    2015-06-01

    Full Text Available This review focuses on the methods available for measuring reversible airways obstruction, bronchial hyperresponsiveness (BHR and inflammation as hallmarks of asthma, and their role in monitoring children with asthma. Persistent bronchial obstruction may occur in asymptomatic children and is considered a risk factor for severe asthma episodes and is associated with poor asthma outcome. Annual measurement of forced expiratory volume in 1 s using office based spirometry is considered useful. Other lung function measurements including the assessment of BHR may be reserved for children with possible exercise limitations, poor symptom perception and those not responding to their current treatment or with atypical asthma symptoms, and performed on a higher specialty level. To date, for most methods of measuring lung function there are no proper randomised controlled or large longitudinal studies available to establish their role in asthma management in children. Noninvasive biomarkers for monitoring inflammation in children are available, for example the measurement of exhaled nitric oxide fraction, and the assessment of induced sputum cytology or inflammatory mediators in the exhaled breath condensate. However, their role and usefulness in routine clinical practice to monitor and guide therapy remains unclear, and therefore, their use should be reserved for selected cases.

  2. Regulation of epithelium-specific Ets-like factors ESE-1 and ESE-3 in airway epithelial cells:potential roles in airway inflammation

    Institute of Scientific and Technical Information of China (English)

    Jing Wu; Martin Post; A Keith Tanswell; Jim Hu; Rongqi Duan; Huibi Cao; Deborah Field; Catherine M Newnham; David R Koehler; Noe Zamel; Melanie A Pritchard; Paul Hertzog

    2008-01-01

    Airway inflammation is the hallmark of many respiratory disorders,such as asthma and cystic fibrosis.Changes in airway gene expression triggered by inflammation play a key role in the pathogenesis of these diseases.Genetic linkage studies suggest that ESE-2 and ESE-3,which encode epithelium-specific Ets-domain-containing transcription factors,are candidate asthma susceptibility genes.We report here that the expression of another member of the Ets family transcription factors ESE-1,as well as ESE-3,is upregulated by the inflammatory cytokines interleukin-1β (IL-1β) and tumor necrosis factor-a (TNF-a) in bronchial epithelial cell lines.Treatment of these cells with IL-1β and TNF-a resulted in a dramatic increase in mRNA expression for both ESE-1 and ESE-3.We demonstrate that the induced expression is mediated by activation of the transcription factor NF-kB.We have characterized the ESE-1 and ESE-3 promoters and have identified the NF-kB binding sequences that are required for the cytokine-induced expression.In addition,we also demonstrate that ESE-1 upregulates ESE-3 expression and downregulates its own induction by cytokines.Finally,we have shown that in Elf3 (homologous to human ESE-1) knockout mice,the expression of the inflammatory cytokine interleukin-6 (IL-6) is downregulated.Our findings suggest that ESE-1 and ESE-3 play an important role in airway inflammation.

  3. Changes of Th17 cytokine in human bronchial epithelial cells induced by coke oven emission%焦炉逸散物致支气管上皮细胞 Th17细胞因子改变

    Institute of Scientific and Technical Information of China (English)

    李红丽; 解秋艳; 刘秀玲; 牛勇; 戴宇飞; 郑玉新; 姚林; 段化伟

    2014-01-01

    OBJECTIVE To find the infla mmation bio markers induced by coke oven e missions (COE),we investigated the changes of T helper 17 (Th17 )cytokines in hu man bronchial epithelial (16HBE)cells.METHODS 16HBE cells were exposed to organic extracts of COE collected fro m co-king plant at the concentrations of 5,10 and 20 mg·L -1 for 24 h or 5 d to establish short-term and long-term cell models,respectively.Cell viability was measured by MTT assay and infla mmatory da mage was assessed by lactate dehydrogenase assay (LDH).The cytokines in culture supernatant sa mples was detected by co mmercial hu man Th17 cytokine panel kit.RESULTS COE Can induce infla mmation in COE 20 mg·L -1 group and no expression on IL-17 F and IL-1 β.The concentration of IL-10 was 1 .25 ± 0.54,1 .39 ±0.13 and (1 .90 ±0.73)pg·mL -1 in COE 5,10 and 20 mg·L -1 group showing good con-centration-effect relationship (r=0.98,P <0.05 ).IL-23 expression was found only higher at 10 and 20 mg·L -1 and the concentrations were 3.38 ±3.90 and (1 .74 ±2.00 )pg·mL -1 ,respectively.In 16HBE cells treated by COE for 5 d,elevated expression of IL-17A was found in COE 5 and 10 mg·L -1 group,and there was statistically sigificant difference between COE 10 mg·L -1 and DMSO group (P<0.05).Elevated concentration of IL-17F of 10.2 ±1 1 .78 and (6.79 ±7.84)pg·mL -1 was found in COE 5 and 10 mg·L -1 group.The concentration of IL-10 was 1 .71 ±0.02,1 .49 ±0.25 and (2.82 ± 0.33)pg·mL -1 in COE 5,10 and 20 mg·L -1 group,respectively.We found increased IL-1 βexpression with concentration of 2.72 ±0.62,2.25 ±0.33 and (0.93 ±0.21 )pg·mL -1 in COE 5,10 and 20 mg·L -1 group with negative dose-response relationship.We also found more elevated TNF-αlevels in the 5 d than in the 24 h model with no COE specific relationship.CONCLUSION COE induces expression changes of Th17 cytokines profile in 16HBE cells,including IL-23 and IL-1 βfor early and long-term infla mmation,respectively.IL-10 may be a candidate

  4. The 5HT1a receptor agonist 8-Oh DPAT induces protection from lipofuscin accumulation and oxidative stress in the retinal pigment epithelium.

    Directory of Open Access Journals (Sweden)

    Prajitha Thampi

    Full Text Available Age-related macular degeneration (AMD, a major cause of blindness in the elderly, is associated with oxidative stress, lipofuscin accumulation and retinal degeneration. The aim of this study was to determine if a 5-HT(1A receptor agonist can reduce lipofuscin accumulation, reduce oxidative damage and prevent retinal cell loss both in vitro and in vivo. Autophagy-derived and photoreceptor outer segment (POS-derived lipofuscin formation was assessed using FACS analysis and confocal microscopy in cultured retinal pigment epithelial (RPE cells in the presence or absence of the 5-HT(1A receptor agonist, 8-OH DPAT. 8-OH DPAT treatment resulted in a dose-dependent reduction in both autophagy- and POS-derived lipofuscin compared to control. Reduction in autophagy-induced lipofuscin was sustained for 4 weeks following removal of the drug. The ability of 8-OH DPAT to reduce oxidative damage following exposure to 200 µM H(2O(2 was assessed. 8-OH DPAT reduced superoxide generation and increased mitochondrial superoxide dismutase (MnSOD levels and the ratio of reduced glutathione to the oxidized form of glutathione in H(2O(2-treated cells compared to controls and protected against H(2O(2-initiated lipid peroxidation, nitrotyrosine levels and mitochondrial damage. SOD2 knockdown mice, which have an AMD-like phenotype, received daily subcutaneous injections of either saline, 0.5 or 5.0 mg/kg 8-OH DPAT and were evaluated at monthly intervals. Systemic administration of 8-OH DPAT improved the electroretinogram response in SOD2 knockdown eyes of mice compared to knockdown eyes receiving vehicle control. There was a significant increase in the ONL thickness in mice treated with 8-OH DPAT at 4 months past the time of MnSOD knockdown compared to untreated controls together with a 60% reduction in RPE lipofuscin. The data indicate that 5-HT(1A agonists can reduce lipofuscin accumulation and protect the retina from oxidative damage and mitochondrial dysfunction. 5-HT

  5. 三氧化二砷诱导人晶状体上皮细胞凋亡的机制研究%Mechanism of arsenic trioxide induced apoptosis in cultured human lens epithelium cells

    Institute of Scientific and Technical Information of China (English)

    张红; 刘平; 于旭辉; 宋甄

    2008-01-01

    Objective To study cytotoxic effects of arsenic trioxide(As2O3)on the human lens epithelium cells and to identify the bioiogical mechanism for these effects.Methods In this experimental study,human lens epithelium cells(FHL124 cells)were cultured in Eagle's minimum essential medium supplemented with 5%fetal calf serum.The effects of As2O3 on FHL124 cells growth were tested by MTT,and apoptosis was detected by TUNEL assay.Gene changes were detected by real-time PCR(Taqman).As2O3-induced changes in cell calcium level were measured by real-time fluorometric single-cell digital imaging techniques after Fura-2 incorporation.Results As2O3 inhibited the growth of FHL 124 cells in vitro in a dose-dependent manner,given an IC50 value of 1.5 μmol/L As2O3 induced apeptosis of FHL124 cells as showed by TUNEL assay.As2O3 provoked an endoplasmic reticulum(ER)stress response identified through an up regulation of EIF2A,ERN1 and ATF6(F=8.51,P=0.0005).As2O3 depleted the calcium store and consequently lead to a decrease of calcium signaling(P=0.0018).Moreover,As2O3 had a modcrate effect on the caicium influx pathway.Conclusions As2O3 inhibits the growth and induces apoptosis of human lens epithelium cells.As2O3 provokes an ER stress which could be the cause of apoptic processes.%目的 研究三氧化二砷(As2O3)对离体培养的人晶状体上皮细胞(FHL124)的凋亡及其作用机制.方法 实验研究.四甲基偶氮唑盐比色法观察As2O3对FHL124细胞的抑制作用;原位缺口末端标记(TUNEL)法测定细胞凋亡;Taqman实时荧光定量PCR检测基因表达的变化;荧光显微镜动态监测细胞内Ca2+浓度的变化.As2O3对FHL124细胞的生长抑制和细胞内Ca2+浓度的变化采用t检验进行分析;3种基因不同处理组间表达水平差异的比较采用Wilks'λ检验;单个基因比较采用LSD-t检验.结果 As2O3(3×10-7~1×10-4mol/L)对FHL124细胞的作用呈浓度依赖性,1 μmol/L As2O3即可显著抑制FHL124细

  6. Using radioaerosols to monitor physiotherapy-enhanced mucus clearance at different levels of the bronchial tree

    Energy Technology Data Exchange (ETDEWEB)

    Hasani, A.; Pavia, D.; Clarke, S.W.; Agnew, J.E. (Royal Free Hospital, London (United Kingdom))

    1993-01-01

    Patients with airways obstruction often find it difficult to clear excess lung secretions. Frequent coughing can clear the larger airways but may itself further damage the airways ciliated epithelium. Various physiotherapy regimes have been proposed yet objective evidence of their efficacy is sparse. Deposited aerosol particles - with an appropriate label for gamma imaging - can track clearance from different lung regions. Published reports have however tended to be equivocal in respect of clearance from the more distal conducting airways. Questions also arise as to coordination of transport rates at different levels of the bronchial tree. We therefore sought to re-assess requirements for effective analysis of physiotherapy-enhanced clearance to yield data on both peripheral and central airways clearance. (author).

  7. Bronchiolitis obliterans organising pneumonia simulating bronchial carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Murphy, J.; Flower, C. [Department of Radiology, Addenbrooke`s Hospital, University of Cambridge Teaching Hospital (United Kingdom); Schnyder, P. [Department of Radiology, University Hospital, Lausanne (Switzerland); Herold, C. [Department of Radiology, University Hospital of Vienna (Austria)

    1998-09-01

    Idiopathic bronchiolitis obliterans organising pneumonia (BOOP) is an uncommon but well-recognised condition that usually presents radiologically as bilateral multifocal patchy areas of consolidation on the chest radiograph and on computed tomography (CT). Five cases are described in which the presenting feature was that of a solitary pulmonary nodule. Four of these nodules showed evidence of cavitation and three patients presented with haemoptysis. In all cases the appearances closely resembled bronchial carcinoma. (orig.) With 5 figs., 21 refs.

  8. Dynamic Properties of Human Bronchial Airway Tissues

    CERN Document Server

    Wang, Jau-Yi; Pallai, Prathap; Corrigan, Chris J; Lee, Tak H

    2011-01-01

    Young's Modulus and dynamic force moduli were measured on human bronchial airway tissues by compression. A simple and low-cost system for measuring the tensile-strengh of soft bio-materials has been built for this study. The force-distance measurements were undertaken on the dissected bronchial airway walls, cartilages and mucosa from the surgery-removed lungs donated by lung cancer patients with COPD. Young's modulus is estimated from the initial slope of unloading force-displacement curve and the dynamic force moduli (storage and loss) are measured at low frequency (from 3 to 45 Hz). All the samples were preserved in the PBS solution at room temperature and the measurements were perfomed within 4 hours after surgery. Young's modulus of the human bronchial airway walls are fond ranged between 0.17 and 1.65 MPa, ranged between 0.25 to 1.96 MPa for cartilages, and between 0.02 to 0.28 MPa for mucosa. The storage modulus are found varying 0.10 MPa with frequency while the loss modulus are found increasing from ...

  9. Ciliary genes are down-regulated in bronchial tissue of primary ciliary dyskinesia patients.

    Directory of Open Access Journals (Sweden)

    Maciej Geremek

    Full Text Available Primary ciliary dyskinesia (PCD is a rare, genetically heterogeneous disease characterized by recurrent respiratory tract infections, sinusitis, bronchiectasis and male infertility. The pulmonary phenotype in PCD is caused by the impaired motility of cilia in the respiratory epithelium, due to ultrastructural defects of these organelles. We hypothesized that defects of multi-protein ciliary complexes should be reflected by gene expression changes in the respiratory epithelium. We have previously found that large group of genes functionally related to cilia share highly correlated expression pattern in PCD bronchial tissue. Here we performed an explorative analysis of differential gene expression in the bronchial tissue from six PCD patients and nine non-PCD controls, using Illumina HumanRef-12 Whole Genome BeadChips. We observed 1323 genes with at least 2-fold difference in the mean expression level between the two groups (t-test p-value <0.05. Annotation analysis showed that the genes down-regulated in PCD biopsies (602 were significantly enriched for terms related to cilia, whereas the up-regulated genes (721 were significantly enriched for terms related to cell cycle and mitosis. We assembled a list of human genes predicted to encode ciliary proteins, components of outer dynein arms, inner dynein arms, radial spokes, and intraflagellar transport proteins. A significant down-regulation of the expression of genes from all the four groups was observed in PCD, compared to non-PCD biopsies. Our data suggest that a coordinated down-regulation of the ciliome genes plays an important role in the molecular pathomechanism of PCD.

  10. Audit of bronchial artery embolisation in a specialist respiratory centre.

    OpenAIRE

    1992-01-01

    OBJECTIVE--To audit the use of bronchial arteriography and embolisation for controlling haemoptysis. DESIGN--Retrospective review of radiological and clinical data. SETTING--Brompton and National Heart Hospitals. PATIENTS--35 patients with severe pulmonary disease in whom 58 bronchial arteriograms were obtained between 1 January 1984 and 31 December 1989 with the intention of bronchial artery embolisation for controlling haemoptysis. MAIN MEASURES--Rate of technical success and cessation of h...

  11. Quantitative morphology and water distribution of bronchial biopsy samples.

    OpenAIRE

    Baldwin, D. R.; Wise, R.; Andrews, J. M.; HONEYBOURNE, D

    1992-01-01

    BACKGROUND: An approach to the study of the pharmacokinetics of drugs in the lung is to measure their concentrations in bronchial biopsy specimens. The main criticism of this technique is that bronchial biopsy specimens consist of more than one tissue type and that drugs are often not distributed evenly. The morphology of bronchial biopsy specimens and the distribution of water between the extracellular and the intracellular compartments is therefore important. METHODS: Fifteen subjects under...

  12. Airway Responsiveness: Role of Inflammation, Epithelium Damage and Smooth Muscle Tension

    Directory of Open Access Journals (Sweden)

    K. I. Gourgoulianis

    1999-01-01

    Full Text Available The purpose of this study was the effect of epithelium damage on mechanical responses of airway smooth muscles under different resting tension. We performed acetylcholine (ACh (10-5M-induced contraction on tracheal strips from 30 rabbits in five groups (0.5, 1, 1.5, 2 and 2.5 g before and after epithelium removal. At low resting tension (0.5-1.5g, the epithelium removal decreased the ACh-induced contractions. At 2g resting tension, the epithelium removal increased the ACh-induced contractions of airways with intact epithelium about 20%. At 2.5 g resting tension, the elevation of contraction is about 25% (p<0.01. Consequently, after epithelium loss, the resting tension determines the airway smooth muscles responsiveness. In asthma, mediators such as ACh act on already contracted inflammatory airways, which results in additional increase of contraction. In contrast, low resting tension, a condition that simulates normal tidal breathing, protects from bronchoconstriction even when the epithelium is damaged.

  13. Differential role of FGF9 on epithelium and mesenchyme in mouse embryonic lung.

    Science.gov (United States)

    del Moral, Pierre-Marie; De Langhe, Stijn P; Sala, Frédéric G; Veltmaat, Jacqueline M; Tefft, Denise; Wang, Kasper; Warburton, David; Bellusci, Savério

    2006-05-01

    Mesothelial Fibroblast Growth Factor 9 (Fgf9) has been demonstrated by inactivation studies in mouse to be critical for the proliferation of the mesenchyme. We now show that Fgf9 is also expressed at significant levels in the distal epithelium from the mid-pseudoglandular stages. Using mesenchymal-free lung endoderm culture, we show that FGF9 triggers the proliferation of the distal epithelium leading to the formation of a cyst-like structure. On embryonic Fgfr2b-/- lungs, FGF9 induces proliferation of the mesenchyme but fails to trigger a similar effect on the epithelium, therefore involving the FGFR2b receptor in the proliferative response of the epithelium to FGF9. While FGF9 inhibits the differentiation of the mesenchyme, the epithelium appears to differentiate normally. At the molecular level, FGF9 up-regulates Fgf10 expression in the mesenchyme likely via increased expression of Tbx4 and 5 and controls the transcription of Hedgehog targets Ptc and Gli-1 in a Hedgehog-independent manner. We also show that FGF9 inhibits the activation of the canonical Wnt pathway in the epithelium by increasing Dkk1 expression, a canonical Wnt antagonist. Our work shows for the first time that FGF9 acts on the epithelium involving FGFR2b to control its proliferation but not its differentiation and contributes to the regulation of canonical Wnt signaling in the epithelium.

  14. The predictive value of bronchial histamine challenge in the diagnosis of bronchial asthma

    DEFF Research Database (Denmark)

    Madsen, F; Holstein-Rathlou, N H; Mosbech, H

    1985-01-01

    A prospective survey aiming to study the predictive value of bronchial histamine challenge was performed on 151 patients with a forced expiratory volume1 (FEV1) above 60% of predicted. According to variations in peak expiratory flow rate (PEFR) and medical history the patients were classified...... was below 0.125 mg/ml the predictive value of a positive test was 1.00, but an increase in PC20 in the range from 4.00 to 16 mg/ml did not increase the predictive value of a negative test. In this study the prevalence of asthma was about 0.6. We therefore conclude that bronchial histamine challenge...

  15. Is platelet activating factor (PAF an important mediator in bronchial asthma?

    Directory of Open Access Journals (Sweden)

    R. H. Gundel

    1992-01-01

    Full Text Available The development of selective PAF receptor antagonists may provide a novel approach to the treatment of human bronchial asthma. In preclinical animal models of human asthma, PAF receptor antagonists have been found to be efficacious in blocking antigen-induced changes in lung function. However, the majority of these models involve acute inflammatory events and transient changes in lung function and, therefore, their relevance to human asthma is questionable. In a recent study with a primate model of chronic airway inflammation and hyperresponsiveness, we have shown that treatment with a PAF receptor antagonist had no effect on reducing chronic inflammation and hyperresponsiveness. Similarly, recent studies in human asthmatics with PAF receptor antagonists have failed to show efficacy in blocking allergen-induced airway responses or to have any steroid sparing effects in patients with ongoing asthma. Thus, it seems that PAF may not be a key mediator which can be blocked and thereby provide therapy for bronchial asthma.

  16. Tight Junctions in Salivary Epithelium

    Directory of Open Access Journals (Sweden)

    Olga J. Baker

    2010-01-01

    Full Text Available Epithelial cell tight junctions (TJs consist of a narrow belt-like structure in the apical region of the lateral plasma membrane that circumferentially binds each cell to its neighbor. TJs are found in tissues that are involved in polarized secretions, absorption functions, and maintaining barriers between blood and interstitial fluids. The morphology, permeability, and ion selectivity of TJ vary among different types of tissues and species. TJs are very dynamic structures that assemble, grow, reorganize, and disassemble during physiological or pathological events. Several studies have indicated the active role of TJ in intestinal, renal, and airway epithelial function; however, the functional significance of TJ in salivary gland epithelium is poorly understood. Interactions between different combinations of the TJ family (each with their own unique regulatory proteins define tissue specificity and functions during physiopathological processes; however, these interaction patterns have not been studied in salivary glands. The purpose of this review is to analyze some of the current data regarding the regulatory components of the TJ that could potentially affect cellular functions of the salivary epithelium.

  17. Effects in cigarette smoke stimulated bronchial epithelial cells of a corticosteroid entrapped into nanostructured lipid carriers

    OpenAIRE

    Bondì, Maria Luisa; Ferraro, Maria; Di Vincenzo, Serena; Gerbino, Stefania; Cavallaro, Gennara; Giammona, Gaetano; Botto, Chiara; Gjomarkaj, Mark; Pace, Elisabetta

    2014-01-01

    Background Nanomedicine studies have showed a great potential for drug delivery into the lung. In this manuscript nanostructured lipid carriers (NLC) containing Fluticasone propionate (FP) were prepared and their biocompatibility and effects in a human bronchial epithelial cell line (16-HBE) stimulated with cigarette smoke extracts (CSE) were tested. Results Biocompatibility studies showed that the NLC did not induce cell necrosis or apoptosis. Moreover, it was confirmed that CSE increased in...

  18. Pranlukast hydrate in the treatment of pediatric bronchial asthma

    Directory of Open Access Journals (Sweden)

    Yoshihara S

    2013-07-01

    Full Text Available Shigemi Yoshihara Department of Pediatrics, Dokkyo Medical University, Tochigi, Japan Abstract: Pranlukast hydrate is a potent, selective, orally active, cysteinyl leukotriene antagonist that binds at the type 1 receptor. It is used as a 10% dry syrup to treat asthma and allergic rhinitis in pediatric patients. In a 4-week, dose-finding study, a dose-dependent improvement in lung function was observed in pediatric patients with asthma at an optimal dose of 5.1–10 mg/kg/day. In a comparative, randomized, double-blind, 4-week multicenter trial, pranlukast dry syrup 7 mg/kg/day achieved significantly better final overall improvement (71.4% versus oxatomide 1 mg/kg/day (37.2% in pediatric patients older than one year with asthma. In two 12-week, open-label trials and in a long-term open-label trial of treatment for up to 24 months, pranlukast dry syrup improved asthma control over baseline values. In a prospective post-marketing surveillance study and a long-term follow-up study, the safety and efficacy of pranlukast dry syrup was confirmed in infants younger than one year with bronchial asthma. In a 4-week, open-label trial, pranlukast dry syrup improved overall health-related quality of life and physical and emotional domain scores over baseline in pediatric patients with asthma. In a randomized, multicenter, double-blind, placebo-controlled, two-period crossover trial, pranlukast dry syrup significantly inhibited exercise-induced bronchospasm in children with asthma compared with placebo. In a modified Childhood Asthma Control Test, pranlukast dry syrup was significantly more effective in controlling asthma in patients younger than 4 years with the common cold. These findings show that pranlukast is useful and beneficial for treating pediatric patients with bronchial asthma. Keywords: pranlukast, leukotriene receptor antagonist, pediatric asthma

  19. Symptoms, physical findings and bronchial hypersensitivity in patients with bronchial asthma and normal spirometry

    Directory of Open Access Journals (Sweden)

    Aćimović Slobodan

    2009-01-01

    Full Text Available Background/Aim. The diagnosis of bronchial asthma, a chronic inflammatory disease of the respiratory tract, is made on the basis of anamnesis, pathologic auscultatory findings of the lungs, lung function disturbances, skin tests, as well as the basic indices of immunologic condition in bronchial trunk. The aim of the study was to find out correlation of objective indices of the disease and than relation with the symptoms in the patients with bronchial asthma. Methods. The study included 60 young male non smokers with long lasting symptoms of bronchial asthma including shortness of breath, wheezing, hard breathing, nonproductive or productive cough, weakness and night hard breathing. There were no symptoms of respiratory infection over the past two months and lung radiography and spirometry were normal. Based on the results of nonspecific bronchoprovocative test two groups of the patients were formed, group I (n = 30 with positive histamine test (average value of the inhaled histamine concentration with FEV1 drop by 20% in regard with the initial value (PC20 = 2.99 ± 0.51 mg/ml of histamine and group II (n = 30 with negative histamine test (PC20(a = 14.58 ± 6.34 mg/ml of histamine. Results. The obtained spirometry results revealed a statistically significant difference in values of FEV1 between groups: I group - FEV1 = 93.2%; II group - FEV1 = 101.8%; (p < 0.05, Wilcoxon test, although all the FEV1 values were normal. Regarding the presence of the most common symptoms there was not statistically significant difference between the groups (p > 0. 05, chisquare test. Pathologic auscultatory lung findings were found in 73.4% of the patients in the group I and 27.5% of the patients in the group II. There was statistically significant difference (p < 0.05, chi-squared test. A positive correlation between the degree of hypersensitivity and lung physical findings was confirmed (p < 0.05 Spearman's rho, but there was no correlation with FEV1 values

  20. Asthma control during the year after bronchial thermoplasty

    DEFF Research Database (Denmark)

    Cox, Gerard; Thomson, Neil C.; Rubin, Adalberto S.

    2007-01-01

    BACKGROUND: Bronchial thermoplasty is a bronchoscopic procedure to reduce the mass of airway smooth muscle and attenuate bronchoconstriction. We examined the effect of bronchial thermoplasty on the control of moderate or severe persistent asthma. METHODS: We randomly assigned 112 subjects who had...

  1. BRONCHOSCOPIC THERAPY IN PATIENTS WITH INTRALUMINAL TYPICAL BRONCHIAL CARCINOID

    NARCIS (Netherlands)

    SUTEDJA, TG; SCHREURS, AJ; VANDERSCHUEREN, RG; KWA, B; VANDERWERF, TS; POSTMUS, PE

    1995-01-01

    Objective: To study the efficacy of bronchoscopic therapy in patients with intraluminal typical bronchial carcinoid. Design: Retrospective analysis of the data of patients with bronchial carcinoid, treated primarily with bronchoscopic techniques such as Nd-YAG laser in various hospitals in the Nethe

  2. Upper respiratory tract disease and bronchial asthma

    Institute of Scientific and Technical Information of China (English)

    1995-01-01

    950302 A synthetical evaluation of occupational asth-ma.LIU Jingyu(刘镜愉),et al.Occup Dis Res Cen-ter,3rd Hosp,Beijing Med Univ,Beijing,100083.ChinJ Industr Hyg & Occouat Dis 1994;12(6)322-325.The occupational exposure and medical history,physical examination,allergen bronchial provocationtest(A-BPT),skin test (ST),specific IgE(S-IgE) andIgG4(S-IgG4) were examined in 43 asthmatic patientswho were suspected to be related to their occupationa

  3. Radioaerosol Inhalation Imaging in Bronchial Asthma

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Bum Soo; Park, Young Ha; Park, Jeong Mi; Chung, Myung Hee; Chung, Soo Kyo; Shinn, Kyung Sub; Bahk, Yong Whee [Catholic University College of Medicine, Seoul (Korea, Republic of)

    1991-03-15

    Radioaerosol inhalation imaging (RII) has been used in radionuclide pulmonary studies for the past 20 years. The method is well accepted for assessing regional ventilation because of its usefulness, easy fabrication and simple application system. To evaluate its clinical utility in the study of impaired regional ventilation in bronchial asthma, we obtained and analysed RIIs in 31 patients (16 women and 15 men; age ranging 21-76 years) with typical bronchial asthma at the Department of Radiology, Kangnam St. Mary's Hospital, Catholic University Medical college, from January, 1988 to August, 1989. Scintiscans were obtained with radioaerosol produced by a HARC(Bhabha Atomic Research Center, India) nebulizer with 15 mCi of {sup 99m}Tc-phytate. The scanning was performed in anterior, posterior and lateral projections following 5-minute inhalation of radioaerosol on sitting position. The scans were analysed and correlated with the results of pulmonary function study and the findings of chest radiography. Fifteen patients had concomitant lung perfusion image with {sup 99m}Tc-MAA. Follow-up scans were obtained in 5 patients after bronchodilator therapy. 1 he patients were divided into (1) attack type (4 patients), (2) resistant type (5 patients), (3) remittent type (10 patients) and (4) bronchitic type (12 patients). Chest radiography showed hyperinflation, altered pulmonary vascularity, thickening of the bronchial wall and accentuation of hasal interstitial markings in 26 of the 31 patients. Chest radiographs were normal in the remaining 5 patients. Regardless of type, the findings of RII were basically the same, and characterized by the deposition of radioaerosol in the central parts or in the main respiratory air ways along with mottled nonsegmental ventilation defects in the periphery. Peripheral parenchymal defects were more extensive than that of expected findings from clinical symptoms, pulmonary function test and chest radiograph. Broomstick sign was present

  4. Bronchial effects of leukotriene D4 inhalation in normal human lung

    DEFF Research Database (Denmark)

    Bisgaard, H; Groth, S

    1987-01-01

    airways in asthmatic patients out of attack. LTD4 caused a dose-dependent obstruction of the airways as measured by partial flow-volume curves and volume of trapped gas, yet only minor changes in forced expiratory volume in 1 s (FEV1) and peak expiratory flow rate. LTD4 was 1900-7000 times more potent...... than histamine. LTD4 inhalations were almost symptomless as opposed to the irritative and dyspnoeic symptoms seen after inhalation of histamine. The time duration for the induced change in partial flow-volume curves was the same for the two drugs. Approximately 30 min elapsed until the bronchial...... not on partial flow-volume curves. Pretreatment with either cimetidine and mepyramine or with indomethacin, did not affect the bronchial obstruction after LTD4.(ABSTRACT TRUNCATED AT 250 WORDS)...

  5. Effects of SO{sub 2} derivatives on expressions of MUC5AC and IL-13 in human bronchial epithelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Li, Ruijin; Meng, Ziqiang [Shanxi University, Institute of Environmental Medicine and Toxicology, Taiyuan (China)

    2007-12-15

    Sulfur dioxide (SO{sub 2}) is a common air pollutant, and inhaled SO{sub 2} in airway epithelium easily forms its soluble derivatives in vivo (bisulfite and sulfite), which are toxic to the respiratory system and related to the exacerbation of asthma. To investigate the effects of SO{sub 2} derivatives on the expressions of asthma related genes (MUC5AC and IL-13), the mRNA and protein levels of the two genes in cultured human bronchial epithelial (BEP2D) cells were analyzed using real-time reverse transcription-polymerase chain reaction (real-time RT-PCR) assay, immunocytochemistry method and enzyme-linked immunosorbent assay (ELISA), respectively. The results showed that the mRNA expressions of MUC5AC and IL-13 were significantly increased at different concentrations of SO{sub 2} derivatives (0.0001, 0.001, 0.01, 0.1 and 1.0 mM), and the maximum appeared at 0.01 mM for MUC5AC (3.9-fold) or at 0.001 mM for IL-13 (4.7-fold). Meanwhile, SO{sub 2} derivatives significantly increased the mRNA levels at 0, 0.5, 1, 4 and 24 h post-exposure with the maximum at 4 h post-exposure (25-fold for MUC5AC and 41-fold for IL-13). Furthermore, the protein levels of MUC5AC and IL-13 in BEP2D cells were significantly increased at different concentrations and different time courses exposed to SO{sub 2} derivatives, along with the maximum at 4 h post-exposure. These results lead to a conclusion that SO{sub 2} derivatives can increase the expressions of MUC5AC and IL-13 genes on the transcription and translation levels, and it suggests that SO{sub 2} derivatives can induce mucus over-production and inflammation responses in human bronchial epithelial cells and may have relations with asthma diseases. This might be one of the possible mechanisms that SO{sub 2} aggravates asthma disease. (orig.)

  6. Metastatic urachal carcinoma in bronchial brush cytology

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    Fatima Zahra Aly

    2013-01-01

    Full Text Available Urachal carcinoma is rare comprising less than 1% of all bladder carcinomas. Metastases of urachal carcinoma have been reported to meninges, brain, ovary, lung, and maxilla. Cytologic features of metastatic urachal carcinoma have not been previously reported. We present a case of metastatic urachal adenocarcinoma in bronchial brushings and review the use of immunohistochemistry in its diagnosis. A 47-year-old female was seen initially in 2007 with adenocarcinoma of the bladder dome for which she underwent partial cystectomy. She presented in 2011 with a left lung mass and mediastinal adenopathy. Bronchoscopy showed an endobronchial lesion from which brushings were obtained. These showed numerous groups of columnar cells with medium sized nuclei and abundant cytoplasm. The cells were positive for CK20 and CDX2 and negative for CK7. The cytomorphological findings were similar to those in the previous resection specimen and concurrent biopsy. This is the first case report of bronchial brushings containing metastatic urachal carcinoma. No specific immunohistochemical profile is available for its diagnosis. The consideration of a second primary was a distinct possibility in this case due to the lapse of time from primary resection, absence of local disease, and lack of regional metastases.

  7. Hydrodynamics of stratified epithelium: steady state and linearized dynamics

    CERN Document Server

    Yeh, Wei-Ting

    2015-01-01

    A theoretical model for stratified epithelium is presented. The viscoelastic properties of the tissue is assumed to be dependent on the spatial distribution of proliferative and differentiated cells. Based on this assumption, a hydrodynamic description for tissue dynamics at long-wavelength, long-time limit is developed, and the analysis reveals important insight for the dynamics of an epithelium close to its steady state. When the proliferative cells occupy a thin region close to the basal membrane, the relaxation rate towards the steady state is enhanced by cell division and cell apoptosis. On the other hand, when the region where proliferative cells reside becomes sufficiently thick, a flow induced by cell apoptosis close to the apical surface could enhance small perturbations. This destabilizing mechanism is general for continuous self-renewal multi-layered tissues, it could be related to the origin of certain tissue morphology and developing pattern.

  8. Hydrodynamics of stratified epithelium: Steady state and linearized dynamics

    Science.gov (United States)

    Yeh, Wei-Ting; Chen, Hsuan-Yi

    2016-05-01

    A theoretical model for stratified epithelium is presented. The viscoelastic properties of the tissue are assumed to be dependent on the spatial distribution of proliferative and differentiated cells. Based on this assumption, a hydrodynamic description of tissue dynamics at the long-wavelength, long-time limit is developed, and the analysis reveals important insights into the dynamics of an epithelium close to its steady state. When the proliferative cells occupy a thin region close to the basal membrane, the relaxation rate towards the steady state is enhanced by cell division and cell apoptosis. On the other hand, when the region where proliferative cells reside becomes sufficiently thick, a flow induced by cell apoptosis close to the apical surface enhances small perturbations. This destabilizing mechanism is general for continuous self-renewal multilayered tissues; it could be related to the origin of certain tissue morphology, tumor growth, and the development pattern.

  9. Bronchial reactivity in hyperresponsive patients and healthy individuals: demonstration with high resolution computed tomography

    Energy Technology Data Exchange (ETDEWEB)

    Schueller, G. E-mail: gerd.schueller@univie.ac.at; Neumann, K.; Helbich, T.; Riemer, H.; Backfrieder, W.; Sertl, K.; Herold, C.J

    2004-11-01

    Objective: High resolution computed tomography (HRCT) was used to assess the extent of bronchial reactivity after inhalative bronchoprovocation and dilation in hyperresponsive patients and healthy subjects. Patients and methods: Patients with mild intermittent asthma, 15 with a >20% decrease in FEV{sub 1} and a >10 mmHg (PC{sub 20}+) in PaO{sub 2}, 12 with a <20% decrease in FEV{sub 1} and a >10 mmHg (PC{sub 20}-) in PaO{sub 2} after provocation, and eight healthy humans were included in the study. Changes in cross-sectional area in a total of 1256 bronchi and in bronchial wall area (792 bronchi) were evaluated after histamine-triggered bronchoprovocation and salbutamol-induced bronchodilation at high lung volumes (FVC 80%). Data were compared with the results of pulmonary function tests (FEV{sub 1}, PaO{sub 2}, PaCO{sub 2}). Results: In all groups, a significant decrease in bronchial cross-sectional area (P<0.001) and a significant increase in bronchial wall area (P<0.001) were observed subsequent to bronchoprovocation. After bronchodilation, the increase in cross-sectional area (P<0.001) and the further increase in airway wall area (P<0.01) were significant in all groups. In PC{sub 20}+ and PC{sub 20}- asthmatics, significant differences (P<0.05) in PaO{sub 2}, >10 mmHg between baseline and provocation were observed. In healthy persons, the PaO{sub 2} decrease was <10 mmHg (P>0.05). After histamine provocation, the decrease in FEV{sub 1} was measured in the PC{sub 20}+ group, whereas a <20% FEV{sub 1} decrease was found in the PC{sub 20}- and the control groups, respectively. No significant correlations were observed between radiological data and the results of pulmonary function tests. Conclusions: HRCT demonstrated bronchial reactivity in hyperresponsive patients and, unexpectedly, in healthy subjects. The applied pulmonary function tests failed to characterize bronchial reactions in the healthy subjects. Based on these results, HRCT is a useful tool by which

  10. Epithelial-mesenchymal transition in primary human bronchial epithelial cells is Smad-dependent and enhanced by fibronectin and TNF-α

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    Câmara Joana

    2010-01-01

    , potentiates EMT in both human alveolar epithelial cells and HBECs. Furthermore, we also show that the collagen discoidin domain receptor 1 (DDR1, generally expressed in epithelial cells, is downregulated during the EMT of bronchial epithelium whereas DDR2 is unaffected. Our results also suggest that bone morphogenetic protein-4 is likely to have a context dependent effect during the EMT of HBECs, being able to induce the expression of EMT markers and, at the same time, to inhibit TGF-β induced epithelial transdifferentiation. Conclusions The results presented in this study provide additional insights into EMT, a potentially very important mechanism in fibrogenesis. We show that, in addition to alveolar epithelial type II cells, primary HBECs are also able to undergo EMT in vitro upon TGF-β1 stimulation via a primarily Smad 2/3 dependent mechanism. The effect of TGF-β1 is potentiated on fibronectin matrix and in the presence of TNF-α, representing a millieu reminiscent of fibrotic lesions. Our results can contribute to a better understanding of lung fibrosis and to the development of new therapeutic approaches.

  11. The junctional epithelium originates from the odontogenic epithelium of an erupted tooth.

    Science.gov (United States)

    Yajima-Himuro, Sara; Oshima, Masamitsu; Yamamoto, Gou; Ogawa, Miho; Furuya, Madoka; Tanaka, Junichi; Nishii, Kousuke; Mishima, Kenji; Tachikawa, Tetsuhiko; Tsuji, Takashi; Yamamoto, Matsuo

    2014-05-02

    The junctional epithelium (JE) is an epithelial component that is directly attached to the tooth surface and has a protective function against periodontal diseases. In this study, we determined the origin of the JE using a bioengineered tooth technique. We transplanted the bioengineered tooth germ into the alveolar bone with an epithelial component that expressed green fluorescence protein. The reduced enamel epithelium from the bioengineered tooth fused with the oral epithelium, and the JE was apparently formed around the bioengineered tooth 50 days after transplantation. Importantly, the JE exhibited green fluorescence for at least 140 days after transplantation, suggesting that the JE was not replaced by oral epithelium. Therefore, our results demonstrated that the origin of the JE was the odontogenic epithelium, and odontogenic epithelium-derived JE was maintained for a relatively long period.

  12. Endoscopic Management of Obstruction due to an Acquired Bronchial Web

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    Kevin L Kovitz

    2002-01-01

    Full Text Available Bronchial webs are thin, membrane-like diaphragms that may obstruct the airway. Several congenital cases have been reported. Though rare, the true incidence of these lesions is probably underestimated because many of them are unrecognized. The case of a 71-year-old woman with an acquired bronchial web causing right main stem bronchus obstruction that went unrecognized for 47 years post-trauma is reported. The lesion was successfully treated using rigid bronchoscopy with laser therapy, balloon dilation and stent placement. This is the first reported case of an acquired bronchial web formation. It is also the first reported case that was successfully treated with this technique.

  13. Autocrine growth factors are involved in branching morphogenesis of mouse lung epithelium.

    Science.gov (United States)

    Okada, Kimiko; Noda, Masatsugu; Nogawa, Hiroyuki

    2013-01-01

    The current model for branching morphogenesis of mouse lung proposes that the epithelium bifurcates as cells pursue separate sources of fibroblast growth factor (FGF) 10, secreted from mesenchymal tissue through interactions with epithelial tissue. If so, it may be assumed that the lung epithelium will grow into a uniform, expanding ball (without branching) when uniformly exposed to a constant concentration of FGF10. To test this hypothesis, we cultured Matrigel-embedded lung epithelium explants in FGF10-supplemented medium while shaking the culture dishes. Shaking cultures with FGF10 resulted in inferior epithelial branching compared to control cultures at rest. However, this effect was unexpectedly accompanied by poor growth rather than by ball-like expansion. When using FGF1, epithelial cultures grew and branched similarly well under either culture condition. Thus, we hypothesized that FGF10 signaling must be mediated by autocrine FGFs, such as FGF1, which might easily diffuse through the culture medium in the shaking culture. Reverse transcription-polymerase chain reaction analyses showed that FGF9 as well as FGF1 were expressed in the epithelium in vivo and in FGF10-stimulated epithelium in vitro, and FGF9 induced epithelial branching at a much lower concentration than FGF10. These results suggest that FGF1 and FGF9 may mediate FGF10 signaling and induce branching in the lung epithelium via autocrine signaling.

  14. Permeability and ultrastructure of human bladder epithelium

    DEFF Research Database (Denmark)

    Eldrup, J; Thorup, Jørgen Mogens; Nielsen, S L;

    1983-01-01

    Leakage of tight junctions as observed with electron microscopy and demonstration of solute transport across bladder epithelium was investigated in 13 patients with different bladder diseases: urinary retention and infection, bladder tumours and interstitial cystitis. The latter group showed cons...

  15. Endocytosis of Multiwalled Carbon Nanotubes in Bronchial Epithelial and Mesothelial Cells

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    Kayo Maruyama

    2015-01-01

    Full Text Available Bronchial epithelial cells and mesothelial cells are crucial targets for the safety assessment of inhalation of carbon nanotubes (CNTs, which resemble asbestos particles in shape. Intrinsic properties of multiwalled CNTs (MWCNTs are known to cause potentially hazardous effects on intracellular and extracellular pathways. These interactions alter cellular signaling and affect major cell functions, resulting in cell death, lysosome injury, reactive oxygen species production, apoptosis, and cytokine release. Furthermore, CNTs are emerging as a novel class of autophagy inducers. Thus, in this study, we focused on the mechanisms of MWCNT uptake into the human bronchial epithelial cells (HBECs and human mesothelial cells (HMCs. We verified that MWCNTs are actively internalized into HBECs and HMCs and were accumulated in the lysosomes of the cells after 24-hour treatment. Next, we determined which endocytosis pathways (clathrin-mediated, caveolae-mediated, and macropinocytosis were associated with MWCNT internalization by using corresponding endocytosis inhibitors, in two nonphagocytic cell lines derived from bronchial epithelial cells and mesothelioma cells. Clathrin-mediated endocytosis inhibitors significantly suppressed MWCNT uptake, whereas caveolae-mediated endocytosis and macropinocytosis were also found to be involved in MWCNT uptake. Thus, MWCNTs were positively taken up by nonphagocytic cells, and their cytotoxicity was closely related to these three endocytosis pathways.

  16. Advances in mechanical ventilation onrespiratoryfailure as a result of chronic obstructive pulmonary disease and bronchial asthma

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    Zhuang MA

    2011-08-01

    Full Text Available Over years,great strides have been made in theories and practices of mechanical ventilation.The indications of non-invasive ventilation have been increasing,while invasive ventilation has been playing a vital role in patients who are critically ill with inadequate drainage of sputum and fail to benefit from non-invasive ventilation.Chronic diseases,including chronic obstructive pulmonary disease(COPD,one of the most common chronic diseases,and bronchial asthma,the incidence of which is ascending recent years,are main causes for respiratory failure.Accordingly,we focus in the present paper on discussion and elaboration of respiratory failure as a result of COPD and bronchial asthma.Type II respiratory failure is the major type of respiratory failure induced by COPD,both in acute exacerbation and stable stage,and mechanical ventilation is one of the most common treatments.Severe acute bronchial asthma complicated with respiratory failure is an emergency.In this situation,primary goal of mechanical ventilation is to make an efficient oxygenation and ventilation of patients,and to avoid hyperinflation to the utmost.For patients who are able to cooperate,non-invasive ventilation in early stage may be beneficial,avoiding tracheal intubation and application of invasive ventilation.But in those who can not achieve remission in a short term,an artificial airway should be established for invasive ventilation as soon as possible.

  17. Cigarette smoke-induced damage-associated molecular pattern release from necrotic neutrophils triggers proinflammatory mediator release.

    Science.gov (United States)

    Heijink, Irene H; Pouwels, Simon D; Leijendekker, Carin; de Bruin, Harold G; Zijlstra, G Jan; van der Vaart, Hester; ten Hacken, Nick H T; van Oosterhout, Antoon J M; Nawijn, Martijn C; van der Toorn, Marco

    2015-05-01

    Cigarette smoking, the major causative factor for the development of chronic obstructive pulmonary disease, is associated with neutrophilic airway inflammation. Cigarette smoke (CS) exposure can induce a switch from apoptotic to necrotic cell death in airway epithelium. Therefore, we hypothesized that CS promotes neutrophil necrosis with subsequent release of damage-associated molecular patterns (DAMPs), including high mobility group box 1 (HMGB1), alarming the innate immune system. We studied the effect of smoking two cigarettes on sputum neutrophils in healthy individuals and of 5-day CS or air exposure on neutrophil counts, myeloperoxidase, and HMGB1 levels in bronchoalveolar lavage fluid of BALB/c mice. In human peripheral blood neutrophils, mitochondrial membrane potential, apoptosis/necrosis markers, caspase activity, and DAMP release were studied after CS exposure. Finally, we assessed the effect of neutrophil-derived supernatants on the release of chemoattractant CXCL8 in normal human bronchial epithelial cells. Cigarette smoking caused a significant decrease in sputum neutrophil numbers after 3 hours. In mice, neutrophil counts were significantly increased 16 hours after repeated CS exposure but reduced 2 hours after an additional exposure. In vitro, CS induced necrotic neutrophil cell death, as indicated by mitochondrial dysfunction, inhibition of apoptosis, and DAMP release. Supernatants from CS-treated neutrophils significantly increased the release of CXCL8 in normal human bronchial epithelial cells. Together, these observations show, for the first time, that CS exposure induces neutrophil necrosis, leading to DAMP release, which may amplify CS-induced airway inflammation by promoting airway epithelial proinflammatory responses.

  18. Comparative cytokeratin distribution patterns in cholesteatoma epithelium.

    Science.gov (United States)

    Olszewska, E; Sudhoff, H

    2007-01-01

    Cytokeratins (CKs) are known as the intermediate filament proteins of epithelial origin. Their distribution in human epithelia is different according to the type of epithelium, state of growth and differentiation. We used monoclonal mouse antibodies against cytokeratins to study CK expression in the following human tissues: cholesteatoma, middle ear mucosa, glandular epithelium, and meatal ear canal epithelium. Immunohistochemical processing was performed using the labeled steptavidin peroxidase method to demonstrate the presence of CKs in cells of human epidermis. Positive reaction was obtained for CK4, CK34betaE12, CK10, CK14 in skin and cholesteatoma epithelium. However, a more extensive positive reaction with those CKs was observed in cholesteatoma epithelium. Positive immunoreactivity was seen with anti- CK19 in the glandular epithelium. Middle ear mucosa specimens revealed positive immunoreactivity with the antibodies against CK4. The expression of CK4 was definitely positive within the basal layers of the epidermis. The glandular epithelium showed no positive reaction with anti- CK4, anti- CK34betaE12, anti- CK14 and anti-CK10. Immunohistochemistry for CK18 showed no reaction in all examined tissues. Cholesteatoma is known as a proliferative disease in the middle ear which pathogenesis is not completely understood. Keratinocytes express hyperproliferation- associated CKs and after reaching the suprabasal layers they finally undergo apoptosis creating keratinous debris. Cytokeratin expression observed in the epithelium explains proliferative behavior of cholesteatoma which is associated with increased keratinocyte migration. Cytokeratins can be used as potential proliferative markers. It can also allow for searching the usefulness of inhibiting regulators in the treatment of hyperproliferative diseases.

  19. Integrin Beta 1 suppresses multilayering of a simple epithelium.

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    Jichao Chen

    Full Text Available Epithelia are classified as either simple, a single cell layer thick, or stratified (multilayered. Stratified epithelia arise from simple epithelia during development, and transcription factor p63 functions as a key positive regulator of epidermal stratification. Here we show that deletion of integrin beta 1 (Itgb1 in the developing mouse airway epithelium abrogates airway branching and converts this monolayer epithelium into a multilayer epithelium with more than 10 extra layers. Mutant lung epithelial cells change mitotic spindle orientation to seed outer layers, and cells in different layers become molecularly and functionally distinct, hallmarks of normal stratification. However, mutant lung epithelial cells do not activate p63 and do not switch to the stratified keratin profile of epidermal cells. These data, together with previous data implicating Itgb1 in regulation of epidermal stratification, suggest that the simple-versus-stratified developmental decision may involve not only stratification inducers like p63 but suppressors like Itgb1 that prevent simple epithelia from inappropriately activating key steps in the stratification program.

  20. 36. Study on p16INK4a and p15INK4b genes of human bronchial epithelial cells malignantly transformed by cyclophosphamide and thiotepa

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    @@Transformed human bronchial epithelial cells BEAS-2B induced by CP and TEPA were used to study abnormity of the tumor suppressor genes p15INK4b and p16INK4a, through which we can provide clues for explanations of the molecular mechanism in carcinogenesis of human bronchial epithelial cells induced by CP and TEPA. Analysis of the genomic DNA from the transformed BEAS-CP, and BEAS-T cells using PCR amplification, singe strand conformation polymorphism(SSCP) and DNA sequencing

  1. Imaging findings of bronchial atresia in fetuses, neonates and infants

    Energy Technology Data Exchange (ETDEWEB)

    Alamo, Leonor; Meuli, Reto [University Hospital of Lausanne (CHUV) and University of Lausanne (UNIL), Department of Diagnostic and Interventional Radiology, Lausanne (Switzerland); Vial, Yvan [University Hospital of Lausanne (CHUV) and University of Lausanne (UNIL), Department of Obstetrics and Gynecology, Lausanne (Switzerland); Gengler, Carole [University Hospital of Lausanne (CHUV) and University of Lausanne (UNIL), Department of Pathology, Lausanne (Switzerland)

    2016-03-15

    Congenital lung malformations are increasingly detected before birth. However, bronchial atresia is rarely identified in utero and not always recognized in neonates. There are two types of atresia: (1) proximal, located at the level of the mainstem or the proximal lobar bronchi, which is extremely rare and usually lethal during pregnancy, causing a tremendous volume increase of the distal involved lung with secondary hypoplasia of the normal lung, and (2) peripheral, located at the segmental/subsegmental bronchial level, which may present as an isolated lesion or as part of a complex congenital malformation. Prenatal findings are mostly nonspecific. Postnatal exams show overinflated lung areas and focal bronchial dilations. The typical fluid-filled bronchoceles are not always observed in neonates but develop progressively in the first months of life. This pictorial essay describes the spectrum of imaging findings of bronchial atresia in fetuses, neonates and infants. (orig.)

  2. A Case of Severe Bronchial Asthma Controlled with Tacrolimus

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    Hirokazu Taniguchi

    2011-01-01

    Full Text Available Background. The control of severe bronchial asthma, such as corticosteroid-resistant asthma, is difficult. It is also possible that immunosuppressive agents would be effective for bronchial asthma. Case Summary. A 55-year-old Japanese female presented with severe bronchial asthma controlled with tacrolimus. She had been diagnosed with bronchial asthma during childhood. Her asthma worsened, and a chest radiograph showed atelectasis of the left lung. Bronchoscopy revealed the left main bronchus to be obstructed with viscous sputum consisting of 82% neutrophils and no eosinophils. The atelectasis did not improve with corticosteroid treatment, but was ameliorated by administration of tacrolimus. Discussion. This patient had severe asthma due to neutrophilic inflammation of the airways. Tacrolimus is effective for treating severe asthma, for example, in corticosteroid-resistant cases.

  3. Undifferentiated bronchial fibroblasts derived from asthmatic patients display higher elastic modulus than their non-asthmatic counterparts.

    Directory of Open Access Journals (Sweden)

    Michal Sarna

    Full Text Available During asthma development, differentiation of epithelial cells and fibroblasts towards the contractile phenotype is associated with bronchial wall remodeling and airway constriction. Pathological fibroblast-to-myofibroblast transition (FMT can be triggered by local inflammation of bronchial walls. Recently, we have demonstrated that human bronchial fibroblasts (HBFs derived from asthmatic patients display some inherent features which facilitate their FMT in vitro. In spite of intensive research efforts, these properties remain unknown. Importantly, the role of undifferentiated HBFs in the asthmatic process was systematically omitted. Specifically, biomechanical properties of undifferentiated HBFs have not been considered in either FMT or airway remodeling in vivo. Here, we combine atomic force spectroscopy with fluorescence microscopy to compare mechanical properties and actin cytoskeleton architecture of HBFs derived from asthmatic patients and non-asthmatic donors. Our results demonstrate that asthmatic HBFs form thick and aligned 'ventral' stress fibers accompanied by enlarged focal adhesions. The differences in cytoskeleton architecture between asthmatic and non-asthmatic cells correlate with higher elastic modulus of asthmatic HBFs and their increased predilection to TGF-β-induced FMT. Due to the obvious links between cytoskeleton architecture and mechanical equilibrium, our observations indicate that HBFs derived from asthmatic bronchi can develop considerably higher static tension than non-asthmatic HBFs. This previously unexplored property of asthmatic HBFs may be potentially important for their myofibroblastic differentiation and bronchial wall remodeling during asthma development.

  4. Undifferentiated bronchial fibroblasts derived from asthmatic patients display higher elastic modulus than their non-asthmatic counterparts.

    Science.gov (United States)

    Sarna, Michal; Wojcik, Katarzyna A; Hermanowicz, Pawel; Wnuk, Dawid; Burda, Kvetoslava; Sanak, Marek; Czyż, Jarosław; Michalik, Marta

    2015-01-01

    During asthma development, differentiation of epithelial cells and fibroblasts towards the contractile phenotype is associated with bronchial wall remodeling and airway constriction. Pathological fibroblast-to-myofibroblast transition (FMT) can be triggered by local inflammation of bronchial walls. Recently, we have demonstrated that human bronchial fibroblasts (HBFs) derived from asthmatic patients display some inherent features which facilitate their FMT in vitro. In spite of intensive research efforts, these properties remain unknown. Importantly, the role of undifferentiated HBFs in the asthmatic process was systematically omitted. Specifically, biomechanical properties of undifferentiated HBFs have not been considered in either FMT or airway remodeling in vivo. Here, we combine atomic force spectroscopy with fluorescence microscopy to compare mechanical properties and actin cytoskeleton architecture of HBFs derived from asthmatic patients and non-asthmatic donors. Our results demonstrate that asthmatic HBFs form thick and aligned 'ventral' stress fibers accompanied by enlarged focal adhesions. The differences in cytoskeleton architecture between asthmatic and non-asthmatic cells correlate with higher elastic modulus of asthmatic HBFs and their increased predilection to TGF-β-induced FMT. Due to the obvious links between cytoskeleton architecture and mechanical equilibrium, our observations indicate that HBFs derived from asthmatic bronchi can develop considerably higher static tension than non-asthmatic HBFs. This previously unexplored property of asthmatic HBFs may be potentially important for their myofibroblastic differentiation and bronchial wall remodeling during asthma development.

  5. [The measurement of bronchial hyperreactivity for military service fitness].

    Science.gov (United States)

    Ferrante, E; Grasso, S; Corbo, G M; Ciappi, G

    1991-10-01

    The authors discuss the efficacy of methacholine challenge to discriminate fit subjects to military service. We evaluated the relation between bronchial hyperreactivity and clinical symptoms, airways caliber and atopic status in a group of italian conscripts who reported to have bronchial asthma. Five-hundred-four subjects were studied. Bronchial hyperreactivity was measured by methacholine test, and atopic status was assessed by skin-tests. A measurable PC20 FEV1 was detected in 424 subjects. On the basis of the methacholine threshold concentration the overall sample was divided in four categories. The four categories differed as regards onset of disease, lung function and skin reactivity towards Dermatophagoides Pter, whereas no difference was found as regards skin reactivity towards Grass. In the group evaluated in spring, the four categories differed as regards skin reactivity towards Grass. In conclusion we found that bronchial hyperreactivity is related to clinical history, lung function and atopic status; the measurement of bronchial hyperreactivity is important to evaluate conscripts referring bronchial asthma.

  6. Bronchial Artery Embolization for Massive Hemoptysis: a Retrospective Study

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    Ali Fani

    2013-05-01

    Full Text Available   Introduction: To assess the efficacy and safety of bronchial artery embolization in the treatment of massive hemoptysis.   Materials and Methods: A retrospective study on 46 patients (26 males and 20 females who were referred to the Razavi Hospital from April 2009 to May 2012 with massive hemoptysis and had bronchial artery embolization procedures. General characteristics of the patients including age, gender, etiology, and thorax computed tomograms, findings of bronchial angiographic, results of the embolization, complications related to bronchial artery embolization and clinical outcome during follow-up were reviewed. Results: The etiology included previous pulmonary tuberculosis in 20 cases, previous tuberculosis with bronchiectasis in 16 cases, bronchiectasis in 6 cases, and active pulmonary tuberculosis in one case. No identifiable causes could be detected in three patients. Moreover, massive hemoptysis was successfully and immediately controlled following the embolization procedure in all patients. One patient developed recurrent hemoptysis during one month following the procedure and was treated by re-embolization. No major procedure–related complication such as bronchial infarction was identified However none of the patientsexperienced neurological complications. Conclusion: Bronchial artery embolization is a safe and effective means of controlling massive hemoptysis and should be regarded as the first-line treatment for this condition.

  7. Importin-α7 is required for enhanced influenza A virus replication in the alveolar epithelium and severe lung damage in mice.

    Science.gov (United States)

    Resa-Infante, Patricia; Thieme, René; Ernst, Thomas; Arck, Petra C; Ittrich, Harald; Reimer, Rudolph; Gabriel, Gülsah

    2014-07-01

    Influenza A viruses recruit components of the nuclear import pathway to enter the host cell nucleus and promote viral replication. Here, we analyzed the role of the nuclear import factor importin-α7 in H1N1 influenza virus pulmonary tropism by using various ex vivo imaging techniques (magnetic resonance imaging, confocal laser scanning microscopy, and correlative light-electron microscopy). We infected importin-α7 gene-deficient (α7(-/-)) mice with a recombinant H1N1 influenza virus and compared the in vivo viral kinetics with those in wild-type (WT) mice. In WT mice, influenza virus replication in the bronchial and alveolar epithelium already occurred a few days after infection. Accordingly, extensive mononuclear infiltration and alveolar destruction were present in the lungs of infected WT mice, followed by 100% lethality. Conversely, in α7(-/-) mice, virus replication was restricted mostly to the bronchial epithelium with marginal alveolar infection, resulting in significantly reduced lung damage and enhanced animal survival. To investigate the host immune response during alveolar virus replication, we studied the role of primary macrophages in virus propagation and clearance. The ability of macrophages to support or clear the virus infection, as well as the host cellular immune responses, did not significantly differ between WT and α7(-/-) mice. However, cytokine and chemokine responses were generally elevated in WT mice, likely reflective of increased viral replication in the lung. In summary, these data show that a cellular factor, importin-α7, is required for enhanced virus replication in the alveolar epithelium, resulting in elevated cytokine and chemokine levels, extensive mononuclear infiltration, and thus, severe pneumonia and enhanced virulence in mice. Importance: Influenza A viruses are respiratory pathogens that may cause pneumonia in humans. Viral infection and replication in the alveoli of the respiratory tract are believed to be crucial for

  8. A microRNA network dysregulated in asthma controls IL-6 production in bronchial epithelial cells.

    Science.gov (United States)

    Martinez-Nunez, Rocio T; Bondanese, Victor P; Louafi, Fethi; Francisco-Garcia, Ana S; Rupani, Hitasha; Bedke, Nicole; Holgate, Stephen; Howarth, Peter H; Davies, Donna E; Sanchez-Elsner, Tilman

    2014-01-01

    MicroRNAs are short non-coding single stranded RNAs that regulate gene expression. While much is known about the effects of individual microRNAs, there is now growing evidence that they can work in co-operative networks. MicroRNAs are known to be dysregulated in many diseases and affect pathways involved in the pathology. We investigated dysregulation of microRNA networks using asthma as the disease model. Asthma is a chronic inflammatory disease of the airways characterized by bronchial hyperresponsiveness and airway remodelling. The airway epithelium is a major contributor to asthma pathology and has been shown to produce an excess of inflammatory and pro-remodelling cytokines such as TGF-β, IL-6 and IL-8 as well as deficient amounts of anti-viral interferons. After performing microRNA arrays, we found that microRNAs -18a, -27a, -128 and -155 are down-regulated in asthmatic bronchial epithelial cells, compared to cells from healthy donors. Interestingly, these microRNAs are predicted in silico to target several components of the TGF-β, IL-6, IL-8 and interferons pathways. Manipulation of the levels of individual microRNAs in bronchial epithelial cells did not have an effect on any of these pathways. Importantly, knock-down of the network of microRNAs miR-18a, -27a, -128 and -155 led to a significant increase of IL-8 and IL-6 expression. Interestingly, despite strong in silico predictions, down-regulation of the pool of microRNAs did not have an effect on the TGF-β and Interferon pathways. In conclusion, using both bioinformatics and experimental tools we found a highly relevant potential role for microRNA dysregulation in the control of IL-6 and IL-8 expression in asthma. Our results suggest that microRNAs may have different roles depending on the presence of other microRNAs. Thus, interpretation of in silico analysis of microRNA function should be confirmed experimentally in the relevant cellular context taking into account interactions with other micro

  9. A microRNA network dysregulated in asthma controls IL-6 production in bronchial epithelial cells.

    Directory of Open Access Journals (Sweden)

    Rocio T Martinez-Nunez

    Full Text Available MicroRNAs are short non-coding single stranded RNAs that regulate gene expression. While much is known about the effects of individual microRNAs, there is now growing evidence that they can work in co-operative networks. MicroRNAs are known to be dysregulated in many diseases and affect pathways involved in the pathology. We investigated dysregulation of microRNA networks using asthma as the disease model. Asthma is a chronic inflammatory disease of the airways characterized by bronchial hyperresponsiveness and airway remodelling. The airway epithelium is a major contributor to asthma pathology and has been shown to produce an excess of inflammatory and pro-remodelling cytokines such as TGF-β, IL-6 and IL-8 as well as deficient amounts of anti-viral interferons. After performing microRNA arrays, we found that microRNAs -18a, -27a, -128 and -155 are down-regulated in asthmatic bronchial epithelial cells, compared to cells from healthy donors. Interestingly, these microRNAs are predicted in silico to target several components of the TGF-β, IL-6, IL-8 and interferons pathways. Manipulation of the levels of individual microRNAs in bronchial epithelial cells did not have an effect on any of these pathways. Importantly, knock-down of the network of microRNAs miR-18a, -27a, -128 and -155 led to a significant increase of IL-8 and IL-6 expression. Interestingly, despite strong in silico predictions, down-regulation of the pool of microRNAs did not have an effect on the TGF-β and Interferon pathways. In conclusion, using both bioinformatics and experimental tools we found a highly relevant potential role for microRNA dysregulation in the control of IL-6 and IL-8 expression in asthma. Our results suggest that microRNAs may have different roles depending on the presence of other microRNAs. Thus, interpretation of in silico analysis of microRNA function should be confirmed experimentally in the relevant cellular context taking into account interactions

  10. Uncoordinated production of Laminin-5 chains in airways epithelium of allergic asthmatics

    Directory of Open Access Journals (Sweden)

    Virtanen Ismo

    2005-09-01

    Full Text Available Abstract Background Laminins are a group of proteins largely responsible for the anchorage of cells to basement membranes. We hypothesized that altered Laminin chain production in the bronchial mucosa might explain the phenomenon of epithelial cell shedding in asthma. The aim was to characterize the presence of Laminin chains in the SEBM and epithelium in allergic and non-allergic asthmatics. Patients and methods Biopsies were taken from the bronchi of 11 patients with allergic and 9 patients with non-allergic asthma and from 7 controls and stained with antibodies against the Laminin (ln chains alpha1-alpha5, beta1-beta2 and gamma1-gamma2. Results Lns-2,-5 and -10 were the main Laminins of SEBM. The layer of ln-10 was thicker in the two asthmatic groups while an increased thickness of lns-2 and -5 was only seen in allergic asthmatics. The ln gamma2-chain, which is only found in ln 5, was exclusively expressed in epithelial cells in association with epithelial injury and in the columnar epithelium of allergic asthmatics. Conclusion The uncoordinated production of chains of ln-5 in allergic asthma could have a bearing on the poor epithelial cell anchorage in these patients.

  11. A Rotating Bioreactor for Scalable Culture and Differentiation of Respiratory Epithelium.

    Science.gov (United States)

    Raredon, Micha Sam Brickman; Ghaedi, Mahboobe; Calle, Elizabeth A; Niklason, Laura E

    2015-10-01

    Respiratory epithelium is difficult to grow in vitro, as it requires a well-maintained polarizing air-liquid interface (ALI) to maintain differentiation. Traditional methods rely on permeable membrane culture inserts, which are difficult to work with and are ill-suited for the production of large numbers of cells, such as the quantities required for cell-based clinical therapies. Herein, we investigate an alternative form of culture in which the cells are placed on a porous substrate that is continuously rolled, such that the monolayer of cells is alternately submerged in media or apically exposed to air. Our prototype bioreactor is reliable for up to 21 days of continuous culture and is designed for scale-up for large-scale cell culture with continuous medium and gas exchange. Normal human bronchial epithelial (NHBE) cells were cultured on an absorbent substrate in the reactor for periods of 7, 14, and 21 days and were compared to static controls that were submerged in media. Quantification by immunohistochemistry and quantitative PCR of markers specific to differentiated respiratory epithelium indicated increased cilia, mucous production, and tight junction formation in the rolled cultures, compared to static. Together with scanning electron microscopy and paraffin histology, the data indicate that the intermittent ALI provided by the rolling bioreactor promotes a polarized epithelial phenotype over a period of 21 days.

  12. Paracellular transport through healthy and cystic fibrosis bronchial epithelial cell lines--do we have a proper model?

    Directory of Open Access Journals (Sweden)

    Natalia Molenda

    Full Text Available It has been reported recently that the cystic fibrosis transmembrane conductance regulator (CFTR besides transcellular chloride transport, also controls the paracellular permeability of bronchial epithelium. The aim of this study was to test whether overexpressing wtCFTR solely regulates paracellular permeability of cell monolayers. To answer this question we used a CFBE41o- cell line transfected with wtCFTR or mutant F508del-CFTR and compered them with parental line and healthy 16HBE14o- cells. Transepithelial electrical resistance (TER and paracellular fluorescein flux were measured under control and CFTR-stimulating conditions. CFTR stimulation significant decreased TER in 16HBE14o- and also in CFBE41o- cells transfected with wtCFTR. In contrast, TER increased upon stimulation in CFBE41o- cells and CFBE41o- cells transfected with F508del-CFTR. Under non-stimulated conditions, all four cell lines had similar paracellular fluorescein flux. Stimulation increased only the paracellular permeability of the 16HBE14o- cell monolayers. We observed that 16HBE14o- cells were significantly smaller and showed a different structure of cell-cell contacts than CFBE41o- and its overexpressing clones. Consequently, 16HBE14o- cells have about 80% more cell-cell contacts through which electrical current and solutes can leak. Also tight junction protein composition is different in 'healthy' 16HBE14o- cells compared to 'cystic fibrosis' CFBE41o- cells. We found that claudin-3 expression was considerably stronger in 16HBE14o- cells than in the three CFBE41o- cell clones and thus independent of the presence of functional CFTR. Together, CFBE41o- cell line transfection with wtCFTR modifies transcellular conductance, but not the paracellular permeability. We conclude that CFTR overexpression is not sufficient to fully reconstitute transport in CF bronchial epithelium. Hence, it is not recommended to use those cell lines to study CFTR-dependent epithelial transport.

  13. Sessile alveolar macrophages communicate with alveolar epithelium to modulate immunity

    Science.gov (United States)

    Westphalen, Kristin; Gusarova, Galina A.; Islam, Mohammad N.; Subramanian, Manikandan; Cohen, Taylor S.; Prince, Alice S.; Bhattacharya, Jahar

    2014-02-01

    The tissue-resident macrophages of barrier organs constitute the first line of defence against pathogens at the systemic interface with the ambient environment. In the lung, resident alveolar macrophages (AMs) provide a sentinel function against inhaled pathogens. Bacterial constituents ligate Toll-like receptors (TLRs) on AMs, causing AMs to secrete proinflammatory cytokines that activate alveolar epithelial receptors, leading to recruitment of neutrophils that engulf pathogens. Because the AM-induced response could itself cause tissue injury, it is unclear how AMs modulate the response to prevent injury. Here, using real-time alveolar imaging in situ, we show that a subset of AMs attached to the alveolar wall form connexin 43 (Cx43)-containing gap junction channels with the epithelium. During lipopolysaccharide-induced inflammation, the AMs remained sessile and attached to the alveoli, and they established intercommunication through synchronized Ca2+ waves, using the epithelium as the conducting pathway. The intercommunication was immunosuppressive, involving Ca2+-dependent activation of Akt, because AM-specific knockout of Cx43 enhanced alveolar neutrophil recruitment and secretion of proinflammatory cytokines in the bronchoalveolar lavage. A picture emerges of a novel immunomodulatory process in which a subset of alveolus-attached AMs intercommunicates immunosuppressive signals to reduce endotoxin-induced lung inflammation.

  14. Justification of advisability of using physical factors in the treatment of patients with allergic rhinitis and associated bronchial asthma

    Directory of Open Access Journals (Sweden)

    T. N. Zaripova

    2012-01-01

    Full Text Available The efficiency of treatment of patients with allergic rhinitis and associated bronchial asthma by physical factors and advisability of two-stage treatment are justified. Sixty six patients were observed. The conclusion on the efficiency of treatment was based on the data about the dynamics clinical state of the primary and associated diseases, intensity of inflammation activity in respiratory tract (rhinocytograms, biochemical indices of nasal lavages, level of nitrogen oxide in expired air were studied, patency of airways (manometry, spirography. We compared two versions of treatment: two- and one-stage. Patients of the first group (30 patients received elimination therapy for 3 to 5 days with the following peaty mud application, current of supersonic frequency, massage, inhalations, physical therapy. Patients of the second group (36 patients did not receive elimination therapy. We have found a decrease in intensity of clinical implications of the primary and associated diseases, decrease in inflammation activity, better nasal and bronchial носовой patency, improvement of the mucociliary function in patients of the first group. In the second group, the recovery of the surface epithelium and nasal patency was not observed against the background of improvement of the clinical state.

  15. Cooling-induced contraction in ovine airways smooth muscle.

    Science.gov (United States)

    Mustafa, S M; Pilcher, C W; Williams, K I

    1999-02-01

    The mechanism of cold-induced bronchoconstriction is poorly understood. This prompted the present study whose aim was to determine the step-wise direct effect of cooling on smooth muscle of isolated ovine airways and analyse the role of calcium in the mechanisms involved. Isolated tracheal strips and bronchial segments were suspended in organ baths containing Krebs' solution for isometric tension recording. Tissue responses during stepwise cooling from 37 to 5 degrees C were examined. Cooling induced a rapid and reproducible contraction proportional to cooling temperature in ovine tracheal and bronchial preparations which was epithelium-independent. On readjustment to 37 degrees C the tone returned rapidly to basal level. Maximum contraction was achieved at a temperature of 5 degrees C for trachea and 15 degrees C for bronchiole. Cooling-induced contractions (CIC) was resistant to tetrodotoxin (1; 10 micrometer), and not affected by the muscarinic antagonist atropine (1 micrometer) or the alpha-adrenergic antagonist phentolamine (1 micrometer), or the histamine H1-antagonist mepyramine (1 micrometer) or indomethacin (1 micrometer). Ca2+ antagonists (nifedipine and verapamil) and Mn2+ raised tracheal but not bronchiolar tone and augmented CIC. Incubation in Ca2+-free, EGTA-containing Krebs' solution for 5 min had no effect on CIC, although it significantly reduced KCl-induced contraction by up to 75%. Cooling inhibited Ca2+ influx measured using 45Ca2+ uptake. Caffeine (100 micrometer) significantly inhibited CIC. The results show that cooling-induced contractions do not appear to involve activation of nerve endings, all surface reception systems or Ca2+ influx. However, CIC is mainly dependent on release of intracellular Ca2+.

  16. Lung epithelium as a sentinel and effector system in pneumonia--molecular mechanisms of pathogen recognition and signal transduction.

    Science.gov (United States)

    Hippenstiel, Stefan; Opitz, Bastian; Schmeck, Bernd; Suttorp, Norbert

    2006-07-08

    Pneumonia, a common disease caused by a great diversity of infectious agents is responsible for enormous morbidity and mortality worldwide. The bronchial and lung epithelium comprises a large surface between host and environment and is attacked as a primary target during lung infection. Besides acting as a mechanical barrier, recent evidence suggests that the lung epithelium functions as an important sentinel system against pathogens. Equipped with transmembranous and cytosolic pathogen-sensing pattern recognition receptors the epithelium detects invading pathogens. A complex signalling results in epithelial cell activation, which essentially participates in initiation and orchestration of the subsequent innate and adaptive immune response. In this review we summarize recent progress in research focussing on molecular mechanisms of pathogen detection, host cell signal transduction, and subsequent activation of lung epithelial cells by pathogens and their virulence factors and point to open questions. The analysis of lung epithelial function in the host response in pneumonia may pave the way to the development of innovative highly needed therapeutics in pneumonia in addition to antibiotics.

  17. Diminished expression of multidrug resistance-associated protein 1 (MRP1) in bronchial epithelium of COPD patients

    NARCIS (Netherlands)

    van der Deen, Margaretha; Marks, Hendrik; Willemse, Brigitte W. M.; Postma, Dirkje S.; Muller, Michael; Smit, Egbert F.; Scheffer, George L.; Scheper, Rik J.; de Vries, Elisabeth G. E.; Timens, Wim

    2006-01-01

    Cigarette smoke is the principal risk factor for chronic obstructive pulmonary disease (COPD). Multidrug resistance proteins, such as multidrug resistance-associated protein-1 (MRP1), P-glycoprotein (P-gp), and lung resistance-related protein (LRP), may protect against oxidative stress and toxic com

  18. Dynamic relationship of the epithelium and mesenchyme during salivary gland initiation: the role of Fgf10

    Directory of Open Access Journals (Sweden)

    Kirsty L. Wells

    2013-08-01

    Salivary glands provide an excellent model for the study of epithelial–mesenchymal interactions. We have looked at the interactions involved in the early initiation and development of murine salivary glands using classic recombination experiments and knockout mice. We show that salivary gland epithelium, at thickening and initial bud stages, is able to direct salivary gland development in non-gland pharyngeal arch mesenchyme at early stages. The early salivary gland epithelium is therefore able to induce gland development in non-gland tissue. This ability later shifts to the mesenchyme, with non-gland epithelium, such as from the limb bud, able to form a branching gland when combined with pseudoglandular stage gland mesenchyme. This shift appears to involve Fgf signalling, with signals from the epithelium inducing Fgf10 in the mesenchyme. Fgf10 then signals back to the epithelium to direct gland down-growth and bud development. These experiments highlight the importance of epithelial–mesenchymal signalling in gland initiation, controlling where, when and how many salivary glands form.

  19. Changes of Interleukin-27, Interleukin-35 and Epstein-Barr virus -induced Gene 3 Expressions in Peripheral Blood of Children with Bronchial Asthma and Its Significance%支气管哮喘患儿外周血 IL-27、IL-35及 EBI3的表达变化及意义

    Institute of Scientific and Technical Information of China (English)

    周月朋; 李俊杰; 李晓东; 王伟; 陶开山; 钱钻好

    2014-01-01

    Objective To investigate the changes of interleukin-27 (IL-27), interleukin-35 (IL-35) and Ep-stein-Barr virus -induced gene 3 (EBI3) expressions in different stages in children with bronchial asthma and its signifi-cance. Methods Seventy-eight children with bronchial asthma (observation group) and seventy-five healthy children (control group) during February 2012 and December 2013 were selected. The samples of peripheral blood were collected in the two groups in the stage of uncontrolled stage, 1 week after partly controlled stage and 1 week after controlled stage. Expression levels of serum IL-27, IL-35 and EBI3 were detected using enzyme-linked immunosorbent test, and the ex-pression levels of IL-27, IL-35 EBI3 and mRNA of mononuclearcell were also detected using real-time fluorescent quanti-tation RT-PCR (reverse transcription polymerase chain reaction) method. Results Levels of serum IL-27 and IL-35 in the stage of uncontrolled stage, 1 week after partly controlled stage and 1 week after controlled stage in observation group were significantly lower than those in control group (P 0. 05). Conclusion The dynamic monitoring of IL-27, IL-35 and mRNA in the peripheral blood and serum level may be used as indexes of control level of asthma in children.%目的:探讨支气管哮喘患儿外周血白介素27(IL-27)、白介素35(IL-35)及 EBI3在不同阶段表达水平的变化及意义。方法采集2012年2月—2013年12月78例支气管哮喘患儿未控制期、部分控制后1周、控制后1周及对照组75例健康儿童外周血,利用酶联免疫吸附试验检测血清中 IL-27及 IL-35的表达水平,并利用实时荧光定量 RT-PCR 的方法检测外周血中单个核细胞中 IL-27、IL-35及 EBI3的 mRNA 的表达情况。结果未控制期、部分控制后1周、控制后1周血清 IL-27、IL-35均明显低于对照组(P 0.05)。结论动态监测外周血中的 IL-27、IL-35 mRNA 及血清水平可以作为儿童哮喘控制水平的指标。

  20. Translocation of the retinal pigment epithelium and choroidal neovascularization induced by injecting Matrigel to subretinal space of rats%大鼠视网膜下注射Matrigel诱导视网膜色素上皮易位和脉络膜新生血管形成

    Institute of Scientific and Technical Information of China (English)

    汪振芳; 万鹏霞; 何丽文; 袁钊辉; 温容

    2007-01-01

    Objective To establish an animal model of sub-retinal pigment epithelium (sub-RPE)deposits,and to explore the pathological process of the transloeation of retinal pigment epithelium, choroidal neovascularization and the pathogenesis of age-related macular degeneration (AMD). Methods Matrigel was injected to the subretinal space of rats to create an amorphous deposit. Translocation of retinal pigment epithelium and choroidal neovascularization were observed. Results The subretinal deposit of Matrigel induced RPE translocation and therefore it became a sub-RPE deposit. The RPE mobilization required the presence of photoreceptors. Bruch's membrane devoid of RPE attachment became vulnerable to the invasion of new blood vessels from the choroid. Conclusions A novel model of sub-RPE deposit formation is established successfully. The presence of sub-RPE deposit is sufficient to induce choroidal neovascularization to penetrate Bruch's membrane and may cause the exudative form of AMD.%目的 制备视网膜色素上皮(RPE)下沉积物形成动物模型,并探讨其诱导视网膜色素上皮易位和脉络膜新牛血管(CNV)形成的病理过程以及年龄相关性黄斑变性(AMD)的发病机制.方法 将Matrigel基质胶注射于大鼠视网膜下形成视网膜下沉积物,观察视网膜色素上皮的迁移和脉络膜新生血管的形成.结果 Matrigel形成视网膜下沉积物后诱导RPE易位,而沉积物换位成为视网膜色素上皮层下沉积物.REP细胞的动员需要光感受器细胞的参与.缺乏色素上皮细胞贴附的Bruch膜易受脉络膜新生血管的侵袭.结论 建立了一个新的视网膜色素上皮层下沉积物形成的AMD动物模型.视网膜色素上皮层下沉积物足以导致CNV穿透Bruch膜,可能导致湿性AMD发生.

  1. Repeated whole cigarette smoke exposure alters cell differentiation and augments secretion of inflammatory mediators in air-liquid interface three-dimensional co-culture model of human bronchial tissue.

    Science.gov (United States)

    Ishikawa, Shinkichi; Ito, Shigeaki

    2017-02-01

    In vitro models of human bronchial epithelium are useful for toxicological testing because of their resemblance to in vivo tissue. We constructed a model of human bronchial tissue which has a fibroblast layer embedded in a collagen matrix directly below a fully-differentiated epithelial cell layer. The model was applied to whole cigarette smoke (CS) exposure repeatedly from an air-liquid interface culture while bronchial epithelial cells were differentiating. The effects of CS exposure on differentiation were determined by histological and gene expression analyses on culture day 21. We found a decrease in ciliated cells and perturbation of goblet cell differentiation. We also analyzed the effects of CS exposure on the inflammatory response, and observed a significant increase in secretion of IL-8, GRO-α, IL-1β, and GM-CSF. Interestingly, secretion of these mediators was augmented with repetition of whole CS exposure. Our data demonstrate the usefulness of our bronchial tissue model for in vitro testing and the importance of exposure repetition in perturbing the differentiation and inflammation processes.

  2. Heterogeneity of the intrahepatic biliary epithelium

    Institute of Scientific and Technical Information of China (English)

    Shannon Glaser; Heather Francis; Sharon DeMorrow; Gene LeSage; Giammarco Fava; Marco Marzioni; Julie Venter; Gianfranco Alpini

    2006-01-01

    The objectives of this review are to outline the recent findings related to the morphological heterogeneity of the biliary epithelium and the heterogeneous pathophysiological responses of different sized bile ducts to liver gastrointestinal hormones and peptides and liver injury/toxins with changes in apoptotic, proliferative and secretory activities. The knowledge of biliary function is rapidly increasing because of the recognition that biliary epithelial cells (cholangiocytes) are the targets of human cholangiopathies, which are characterized by proliferation/damage of bile ducts within a small range of sizes. The unique anatomy, morphology, innervation and vascularization of the biliary epithelium are consistent with function of cholangiocytes within different regions of the biliary tree. The in vivo models [e.g., bile duct ligation (BDL), partial hepatectomy, feeding of bile acids,carbon tetrachloride (CCl4) or α-naphthylisothiocyanate (ANIT)] and the in vivo experimental tools [e.g., freshly isolated small and large cholangiocytes or intrahepatic bile duct units (IBDU) and primary cultures of small and large murine cholangiocytes] have allowed us to demonstrate the morphological and functional heterogeneity of the intrahepatic biliary epithelium.These models demonstrated the differential secretory activities and the heterogeneous apoptotic and proliferative responses of different sized ducts. Similar to animal models of cholangiocyte proliferation/injury restricted to specific sized ducts, in human liver diseases bile duct damage predominates specific sized bile ducts.Future studies related to the functional heterogeneity of the intrahepatic biliary epithelium may disclose new pathophysiological treatments for patients with cholangiopathies.

  3. Recurrent pneumothorax associated with bronchial atresia: report of a case.

    Science.gov (United States)

    Tanaka, Kazuhisa; Suzuki, Hidemi; Nakajima, Takahiro; Tagawa, Tetsuzo; Iwata, Takekazu; Mizobuchi, Teruaki; Yoshida, Shigetoshi; Yoshino, Ichiro

    2015-10-01

    We herein report a case of recurrent pneumothorax associated with congenital bronchial atresia. A 26-year-old male presented with chest pain. Chest roentgenograms showed left pneumothorax, a left apical bulla and an area of hyperlucency in the left upper lung field, and chest computed tomography revealed a discontinuation of the left superior bronchus. Additionally, both ventilation and perfusion scintigraphy showed a defect in the left superior segment. A thoracoscopy-assisted left superior segmentectomy was performed, and a pathological examination indicated left superior segmental bronchial atresia, which might have predisposed the peripheral lung to emphysematous conditions. No relapse was observed 6 months after the operation. Although this entity is rare, congenital bronchial atresia should be considered in the differential diagnosis when a patient has suffered from a recurrent spontaneous pneumothorax.

  4. IMMUNOLOGICAL AND PSYCHOPHYSIOLOGICAL HETEROGENEITY AMONG PATIENTS WITH BRONCHIAL ASTHMA

    Directory of Open Access Journals (Sweden)

    A. V. Smyk

    2008-01-01

    Full Text Available Abstract. Bronchial asthma is a classic psychosomatic disease by immunopathological origin. In present investigation, we studied influence of body-oriented psychotherapeutic methods directed towards clinico-immunological parameters and special psychological features of the patients with bronchial asthma, i.e., decrease in alexithymia, as an important pathogenetic factor of bronchial asthma, and improvement in motor coordination and interhemispheric interactions in motor sphere. We investigated 38 patients (18 men and 20 women, while discriminating those patients who underwent a course of body-oriented psychotherapy, and a group of comparison, who did not undergo similar therapy. When observing conventional standards of randomization according to sex, age, clinical variants, and disease severity, some heterogeneity of these groups was revealed. In general, the people with active life attitude, being ready to work with a psychologist, possessed special features both in psychological and immunological spheres.

  5. Changes of the lingual epithelium in Ambystoma mexicanum.

    Science.gov (United States)

    Wistuba, J; Clemen, G

    1998-12-01

    Changes in the lingual epithelium during ontogenesis and after induced metamorphosis in Ambystoma mexicanum are described as observed by light microscopy and scanning electron microscopy. The epithelium of the tongue is always multilayered in the larva as well as in the adult. It consists of a stratum germinativum with little differentiated basal cells and a stratum superficiale (superficial layer) with specialized superficial cells and goblet cells. Usually, there are more than two layers because of a stratum intermedium consisting of replacement cells. The apical cell membrane of the superficial cells is perforated by fine pores. Its most typical feature are microridges. Maturing superficial cells possess microvilli. Goblet cells occur in early larvae primarily in the centre of the tongue. They spread throughout the dorsal face of the tongue as their numbers increase during ontogenesis. The small apices of the goblet cells are intercalated in the wedges between the superficial cells. Leydig cells are not found on the larval tongue but on that of adults. Due to metamorphosis, the epithelium of the tongue changes. It is furrowed in its anterior part. The furrows house the openings of the lingual glands. The surface is further modulated by ridges which are densely coated by microvilli and which bear the taste buds. The villi of the tongue which lack extrusion pores show cilia and microvilli but lack microridges. The Leydig cells disappear during metamorphosis. In addition to the two types of goblet cells found in different regions of the glandular tubules, goblet cells occur in the caudal part. They secrete directly into the cavity of the mouth. The posterior part is characterised by a dense coat of cilia.

  6. Empirical description of bronchial and nonbronchial arteries with MDCT

    Energy Technology Data Exchange (ETDEWEB)

    Yu Hong, E-mail: yuhong.2002@hotmail.co [Department of Imageology, Changzheng hospital, Second Military Medical University, Shanghai 200003 (China); Liu Shiyuan, E-mail: cjr.liushiyuan@vip.163.co [Department of Imageology, Changzheng hospital, Second Military Medical University, Shanghai 200003 (China); Li Huimin, E-mail: yuhongphd@163.co [Department of Imageology, Changzheng hospital, Second Military Medical University, Shanghai 200003 (China); Xiao Xiangsheng, E-mail: cjr.xxsh@vip.163.co [Department of Imageology, Changzheng hospital, Second Military Medical University, Shanghai 200003 (China); Dong Weihua, E-mail: dongweihua2000@163.co [Department of Imageology, Changzheng hospital, Second Military Medical University, Shanghai 200003 (China)

    2010-08-15

    Purpose: We aimed to retrospectively evaluate bronchial and nonbronchial systemic arteries using multi-detector row helical computed tomographic (MDCT) angiography in patients with pulmonary disorders. Materials and Methods: Thirty-nine patients (24 men, 15 women; mean age, 63.4 years; range, 20-82 years) with congenital and acquired pulmonary disorders of the bronchial and nonbronchial systemic arteries underwent multi-detector row helical computed tomographic angiography of the thorax using a 16-detector row scanner. Each of these patients had experienced an episode of hemoptysis. Computed tomographic angiogram data, which included maximum intensity projections, multiplanar reconstruction, and three-dimensional volume-rendered images, were used to retrospectively analyse the characteristics of the bronchial and nonbronchial systemic arteries. Results: We identified a total of 128 bronchial arteries (76 on the right side and 52 on the left) in 39 patients. We detected 42 nonbronchial systemic artery branches, including 19 internal mammary artery branches, 8 subclavian artery branches, 8 inferior phrenic artery branches, 5 intercostal artery branches, 1 thyrocervical trunk branch, and 1 celiac trunk branch. Thirty-five dilated and tortuous nonbronchial systemic arteries entered into the lung parenchyma and extended down to the lesions. Every case, except the one case of sequestration, was associated with pleural thickening where the vascular structures passed through the extrapleural fat. Conclusions: The variations in both the bronchial artery anatomy and the location and type of the nonbronchial arteries were great. Nonbronchial arteries may be a significant source of hemoptysis. MDCT angiography can be used to detect detailed anatomical information about the origins and courses of bronchial and nonbronchial systemic arteries and their pathophysiologic features.

  7. Bronchial Sparganosis mansoni accompanied by abnormal hyperplasia diagnosed by bronchoscopy

    Institute of Scientific and Technical Information of China (English)

    BAI Jing; HE Zhi-yi; LIU Guang-nan; ZHANG Jian-quan; DENG Jing-min; LI Mei-hua; ZHONG Xiao-ning

    2012-01-01

    Pulmonary sparganosis mansoni is rare in humans and bronchial sparganosis mansoni has not been reported.We reported a patient with a soft-tissue mass in the right hilum area on a chest computed tomography (CT) scan that was suspected of being lung cancer.Bronchoscopy identified sparganum larvae.Bronchial sparganosis mansoni accompanied by abnormal hyperplasia was diagnosed by histopathology.We introduced our experience and reviewed the clinical characteristics of three pulmonary sparganosis mansoni cases and three pleural cavity sparganosis mansoni cases that have been reoorted.

  8. Exhaled Eicosanoids following Bronchial Aspirin Challenge in Asthma Patients with and without Aspirin Hypersensitivity: The Pilot Study

    Directory of Open Access Journals (Sweden)

    L. Mastalerz

    2012-01-01

    Full Text Available Background. Special regulatory role of eicosanoids has been postulated in aspirin-induced asthma. Objective. To investigate effects of aspirin on exhaled breath condensate (EBC levels of eicosanoids in patients with asthma. Methods. We determined EBC eicosanoid concentrations using gas chromatography/mass spectrometry (GC-MS and high-performance liquid chromatography/mass spectrometry (HPLC-MS2 or both. Determinations were performed at baseline and following bronchial aspirin challenge, in two well-defined phenotypes of asthma: aspirin-sensitive and aspirin-tolerant patients. Results. Aspirin precipitated bronchial reactions in all aspirin-sensitive, but in none of aspirin-tolerant patients (ATAs. At baseline, eicosanoids profile did not differ between both asthma groups except for lipoxygenation products: 5- and 15-hydroxyeicosatetraenoic acid (5-, 15-HETE which were higher in aspirin-induced asthma (AIA than inaspirin-tolerant subjects. Following aspirin challenge the total levels of cysteinyl-leukotrienes (cys-LTs remained unchanged in both groups. The dose of aspirin had an effect on magnitude of the response of the exhaled cys-LTs and prostanoids levels only in AIA subjects. Conclusion. The high baseline eicosanoid profiling of lipoxygenation products 5- and 15-HETE in EBC makes it possible to detect alterations in aspirin-sensitive asthma. Cysteinyl-leukotrienes, and eoxins levels in EBC after bronchial aspirin administration in stable asthma patients cannot be used as a reliable diagnostic index for aspirin hypersensitivity.

  9. Cystic fibrosis bronchial epithelial cells are lipointoxicated by membrane palmitate accumulation.

    Directory of Open Access Journals (Sweden)

    Laurie-Anne Payet

    Full Text Available The F508del-CFTR mutation, responsible for Cystic Fibrosis (CF, leads to the retention of the protein in the endoplasmic reticulum (ER. The mistrafficking of this mutant form can be corrected by pharmacological chaperones, but these molecules showed limitations in clinical trials. We therefore hypothesized that important factors in CF patients may have not been considered in the in vitro assays. CF has also been associated with an altered lipid homeostasis, i. e. a decrease in polyunsaturated fatty acid levels in plasma and tissues. However, the precise fatty acyl content of membrane phospholipids from human CF bronchial epithelial cells had not been studied to date. Since the saturation level of phospholipids can modulate crucial membrane properties, with potential impacts on membrane protein folding/trafficking, we analyzed this parameter for freshly isolated bronchial epithelial cells from CF patients. Interestingly, we could show that Palmitate, a saturated fatty acid, accumulates within Phosphatidylcholine (PC in CF freshly isolated cells, in a process that could result from hypoxia. The observed PC pattern can be recapitulated in the CFBE41o(- cell line by incubation with 100 µM Palmitate. At this concentration, Palmitate induces an ER stress, impacts calcium homeostasis and leads to a decrease in the activity of the corrected F508del-CFTR. Overall, these data suggest that bronchial epithelial cells are lipointoxicated by hypoxia-related Palmitate accumulation in CF patients. We propose that this phenomenon could be an important bottleneck for F508del-CFTR trafficking correction by pharmacological agents in clinical trials.

  10. Prostaglandin E2 release from dermis regulates sodium permeability of frog skin epithelium

    DEFF Research Database (Denmark)

    Rytved, Klaus A.; Brodin, Birger; Nielsen, Robert

    1995-01-01

    Arachidonic acid, cAMP, epithelium, frog skin, intracellular calcium, prostaglandin E*U2, sodium transport, tight epithelium.......Arachidonic acid, cAMP, epithelium, frog skin, intracellular calcium, prostaglandin E*U2, sodium transport, tight epithelium....

  11. Passive sensitization increases histamine-stimulated calcium signaling and NF-кB transcription activity in bronchial epithelial cells

    Institute of Scientific and Technical Information of China (English)

    Si JIN; Dan TIAN; Jian-guo CHEN; Li-ping ZHU; Sheng-yuan LIU; Di-xun WANG

    2006-01-01

    Aim: To find out if the two aspects of asthma (chronic airway inflammation and bronchial hyperresponsiveness) are related to hypersensitivity of calcium signaling in bronchial epithelial cells. Methods: Porcine bronchial epithelial cells (PBEC) were divided into sensitized (S) and nonsesitized (N) groups. In group S, the cells were preincubated with serum from ovalbumin sensitized guinea pigs. In group N, the cells were preincubated with serum from nonsensitized guinea pigs. Single cell calcium imaging and ELISA-based NF-κB activity were used to evaluate the histamine-stimulated intracellular free calcium level and NF-κB activity, respectively. Results: First, 0.1 umol/L histamine could induce [Ca2+]i oscillations in PBEC of group S, but not in group N. Second, 1 umol/L histamine could induce [Ca2+]i oscillations of PBEC in both group S and group N. The [Ca2+]i oscillation frequency of PBEC was significantly higher in group S than in group N, though the [Ca2+]i oscillation amplitude showed no difference between the two groups. Finally, when 10 umol/L histamine was used to stimulate PBEC, a transient initial increase followed by a sustained elevation (FSE) of [Ca2+]i was observed in PBEC in both groups. The amplitude of the FSE of [Ca2+]i in PBEC was significantly higher in group S than in group N. The subsequent NF-KB activity was in accordance to the calcium oscillation frequency evoked by histamine, but not to the amplitude. Conclusion: It was suggested that the increased sensitivity of calcium signaling in bronchial epithelial cells might contribute to the exorbitant inflammation or increased susceptibility in asthmatic airway epithelial cells.

  12. Occupational allergic airbone contact dermatitis and delayed bronchial asthma from epoxy resin revealed by bronchial provocation test.

    Science.gov (United States)

    Kanerva, L; Estlander, T; Keskinen, H; Jolanki, R

    2000-08-01

    Diglycidyl ether of bisphenol A (DGEBA) epoxy resins belong to the most common causes of occupational allergic contact dermatitis. DGEBA has on rare occasions caused occupational asthma. Here we present a patient who first developed occupational allergic contact dermatitis (ACD) caused by a single accidental exposure to DGEBA. Then, on continued occupational exposure to DGEBA, the patient developed occupational asthma from DGEBA, in addition to ACD. A bronchial provocation test with DGEBA caused a 36% drop in the peak expiratory flow, reflecting a delayed type of occupational asthma. This bronchial provocation test caused a strong dermatitis of the exposed skin of the face, in accordance with airborne ACD from DGEBA.

  13. Comparison of bronchial brushing and sputum in detection of pediatric pulmonary tuberculosis.

    Science.gov (United States)

    Chen, Qiao-Pei; Ren, Shi-Feng; Wang, Xin-Feng; Wang, Mao-Shui

    2016-01-27

    The retrospective study aimed to evaluate the diagnostic value of bronchial brushing and sputum using acid fast bacilli smear, mycobacterial culture and real-time PCR in detection of pediatric pulmonary tuberculosis, sensitivity and specificity of bronchial brushing and sputum examined by the three methods were calculated and compared to each other. Data showed there were no significant difference in sensitivity between bronchial brushing and matched sputum using each method. But the specificity of real-time PCR on bronchial brushing was lower than on sputum. Compared with bronchial brushing, sputum was better specimen in detection of pediatric pulmonary tuberculosis.

  14. [Determination of tumor infiltration of the bronchial wall in lung cancer].

    Science.gov (United States)

    Utkin, V V; Ozols, A Ia; Marga, O Ia

    1975-01-01

    In the article, a new method of diagnosing the extent of the tumor spread in the bronchial wall without involvement of the mucosa (a peripbronchial form of the growth) is described. The method consists of two components - angiography of bronchial arteries with subsequent injection of a staining material in the corresponding bronchial artery and bronchoscopy, by means of which staining of the mucous membrane of the bronchial tree is observed. In case of tumor infiltration of the bronchial wall staining was absent completely or partially. A clinical trial of the method indicated its high efficacy.

  15. Intestinal epithelium in inflammatory bowel disease

    Directory of Open Access Journals (Sweden)

    Mehmet eCoskun

    2014-08-01

    Full Text Available The intestinal epithelium has a strategic position as a protective physical barrier to luminal microbiota and actively contributes to the mucosal immune system. This barrier is mainly formed by a monolayer of specialized intestinal epithelial cells (IECs that are crucial in maintaining intestinal homeostasis. Therefore, dysregulation within the epithelial layer can increase intestinal permeability, lead to abnormalities in interactions between IECs and immune cells in underlying lamina propria, and disturb the intestinal immune homeostasis, all of which are linked to the clinical disease course of inflammatory bowel disease (IBD. Understanding the role of the intestinal epithelium in IBD pathogenesis might contribute to an improved knowledge of the inflammatory processes and the identification of potential therapeutic targets.

  16. Intestinal epithelium in inflammatory bowel disease

    DEFF Research Database (Denmark)

    Coskun, Mehmet

    2014-01-01

    The intestinal epithelium has a strategic position as a protective physical barrier to luminal microbiota and actively contributes to the mucosal immune system. This barrier is mainly formed by a monolayer of specialized intestinal epithelial cells (IECs) that are crucial in maintaining intestinal...... homeostasis. Therefore, dysregulation within the epithelial layer can increase intestinal permeability, lead to abnormalities in interactions between IECs and immune cells in underlying lamina propria, and disturb the intestinal immune homeostasis, all of which are linked to the clinical disease course...... of inflammatory bowel disease (IBD). Understanding the role of the intestinal epithelium in IBD pathogenesis might contribute to an improved knowledge of the inflammatory processes and the identification of potential therapeutic targets....

  17. [Neutrophils and monocytes in gingival epithelium

    Science.gov (United States)

    Meng, H X; Zheng, L P

    1994-06-01

    Neutrophils and monocytes of gingival epithellium in health gingiva(H),marginal gingivitis(MG),juvenile periodontitis(JP),adult periodontitis(AP) and subgingival bacteria were quantitated and analyzed,The results showed that the numbers of PMN within either pocket epithelium or oral gingival epithelium in JP were significantly lower than in AP and G.The amounts of PMN in AP were much larger than other three groups.Positive correlation between the number of PMN in sulcular pocket epitelium and the motile bacteri of subgingival plaque was demonstrated by correlation analysis.Monocytes mainly presented in deep pocket and junctional epithelum which were stained by NAE method,however very few Langhans cells were seen in these areas.

  18. Lung alveolar epithelium and interstitial lung disease.

    Science.gov (United States)

    Corvol, Harriet; Flamein, Florence; Epaud, Ralph; Clement, Annick; Guillot, Loic

    2009-01-01

    Interstitial lung diseases (ILDs) comprise a group of lung disorders characterized by various levels of inflammation and fibrosis. The current understanding of the mechanisms underlying the development and progression of ILD strongly suggests a central role of the alveolar epithelium. Following injury, alveolar epithelial cells (AECs) may actively participate in the restoration of a normal alveolar architecture through a coordinated process of re-epithelialization, or in the development of fibrosis through a process known as epithelial-mesenchymal transition (EMT). Complex networks orchestrate EMT leading to changes in cell architecture and behaviour, loss of epithelial characteristics and gain of mesenchymal properties. In the lung, AECs themselves may serve as a source of fibroblasts and myofibroblasts by acquiring a mesenchymal phenotype. This review covers recent knowledge on the role of alveolar epithelium in the pathogenesis of ILD. The mechanisms underlying disease progression are discussed, with a main focus on the apoptotic pathway, the endoplasmic reticulum stress response and the developmental pathway.

  19. Odors Discrimination by Olfactory Epithelium Biosensor

    Science.gov (United States)

    Liu, Qingjun; Hu, Ning; Ye, Weiwei; Zhang, Fenni; Wang, Hua; Wang, Ping

    2011-09-01

    Humans are exploring the bionic biological olfaction to sense the various trace components of gas or liquid in many fields. For achieving the goal, we endeavor to establish a bioelectronic nose system for odor detection by combining intact bioactive function units with sensors. The bioelectronic nose is based on the olfactory epithelium of rat and microelectrode array (MEA). The olfactory epithelium biosensor generates extracellular potentials in presence of odor, and presents obvious specificity under different odors condition. The odor response signals can be distinguished with each other effectively by signal sorting. On basis of bioactive MEA hybrid system and the improved signal processing analysis, the bioelectronic nose will realize odor discrimination by the specific feature of signals response to various odors.

  20. Morgagni’s hernia in a woman with bronchial asthma

    Directory of Open Access Journals (Sweden)

    Gowrinath K

    2014-07-01

    Full Text Available A 59-year-old, other wise asymptomatic lady known to have bronchial asthma was found to have an anterior mediastinal mass on a chest radiograph incidentally obtained as a part of pre-operative work-up for cataract surgery. Computed tomography of the chest confirmed the diagnosis of Morgagni’s hernia.

  1. Lung function, bronchial hyperresponsiveness, and atopy among firefighters

    NARCIS (Netherlands)

    Greven, Frans; Krop, Esmeralda; Spithoven, Jack; Rooyackers, Jos; Kerstjens, Huib; Heederik, Dick

    2011-01-01

    Objectives The aim of this study was to determine associations between lung function, bronchial hyperresponsiveness (BHR), and atopy with exposure to fire smoke among firefighters. Methods The study was comprised of 402 firefighters, a randomly chosen subset of a previous survey among firefighters i

  2. Dry powder formulation in the twincertm for bronchial challenge testing

    NARCIS (Netherlands)

    Lexmond, A.J.; Hagedoorn, P.; Frijlink, H.W.; Ten Hacken, N.H.T.; Steckel, H.; De Boer, A.H.

    2013-01-01

    Summary Background: In bronchial challenge testing lung deposition of the stimulus may be poorly controlled due to incorrect use of nebulisers. Furthermore, the need for freshly prepared solutions burdens personnel and budget. In this study we aim to develop a dry powder alternative with higher repr

  3. Assessment of Serum Vitamin D in Patients with Bronchial Asthma

    Directory of Open Access Journals (Sweden)

    Hisham E. Abd El Aaty

    2015-01-01

    Conclusions: Vitamin D deficiency was highly prevalent in asthmatic patients, there was a strong correlation between asthma severity and 25(OH vitamin D concentrations and there was a direct and a positive significant correlation between vitamin D levels and pulmonary function tests in asthmatic patients, so the measurement of serum vitamin D levels in patients with bronchial asthma is very useful.

  4. In vivo models of human airway epithelium repair and regeneration

    Directory of Open Access Journals (Sweden)

    C. Coraux

    2005-12-01

    Full Text Available Despite an efficient defence system, the airway surface epithelium, in permanent contact with the external milieu, is frequently injured by inhaled pollutants, microorganisms and viruses. The response of the airway surface epithelium to an acute injury includes a succession of cellular events varying from the loss of the surface epithelium integrity to partial shedding of the epithelium or even to complete denudation of the basement membrane. The epithelium has then to repair and regenerate to restore its functions. The in vivo study of epithelial regeneration in animal models has shown that airway epithelial cells are able to dedifferentiate, spread, migrate over the denuded basement membrane and progressively redifferentiate to reconstitute a functional respiratory epithelium after several weeks. Humanised tracheal xenograft models have been developed in immunodeficient nude and severe combined immunodeficient (SCID mice in order to mimic the natural regeneration process of the human airway epithelium and to analyse the cellular and molecular events involved during the different steps of airway epithelial reconstitution. These models represent very powerful tools for analysing the modulation of the biological functions of the epithelium during its regeneration. They are also very useful for identifying stem/progenitor cells of the human airway epithelium. A better knowledge of the mechanisms involved in airway epithelium regeneration, as well as the characterisation of the epithelial stem and progenitor cells, may pave the way to regenerative therapeutics, allowing the reconstitution of a functional airway epithelium in numerous respiratory diseases, such as asthma, chronic obstructive pulmonary diseases, cystic fibrosis and bronchiolitis.

  5. 单核巨噬细胞在煤焦沥青烟提取物诱导永生化人支气管上皮细胞恶变中的作用%The Effects of monocyte-macrophages on malignant transformation of human bronchial epithelial cells induced by extracts from coal tar pitch

    Institute of Scientific and Technical Information of China (English)

    周凡静; 张少峰; 冯斐斐; 燕贞; 王威; 吴逸明

    2012-01-01

    目的 探讨单核巨噬细胞(THP-1)在煤焦沥青烟提取物(coal tar pitch,CTP)致永生化人支气管上皮细胞(human bronchial epithelial cells,BEAS-2B)恶变过程中的作用及肿瘤坏死因子α(tumor necrosis factor alpha,TNF-α)在该过程中的表达.方法 以THP-1和BEAS-2B为研究对象,设立CTP组、苯并(a)芘[B(a)P]组(阳性对照组)、二甲亚砜对照组(溶剂对照组)、BEAS-2B与THP-1共培养组,建立细胞恶性变模型.应用软琼脂集落形成实验、染色体数目畸变分析、流式细胞仪测定细胞周期中不同培养时期(10、20、30代)细胞的恶变情况,利用ELISA方法测定CTP组及共培养组细胞培养上清中TNF-α的含量.结果 染色体数目异常在实验的早期(10代)已经显现,表现为非整倍体和多倍体比例增加,二倍体数目减少.在第20代:共培养组克隆形成率(17.63‰±0.97‰)明显高于CTP组(13.94‰±0.84‰)和阳性对照组组(12.96‰± 1.62‰),差异有统计学意义(P<0.05);共培养组S期细胞比例(44.49%±0.68%)明显高于CTP组(38.19%±1.26%)和阳性对照组(36.41%±1.19%),差异有统计学意义(P<0.05).共培养组细胞培养上清中TNF-α含量明显高于CTP组,差异有统计学意义(P<0.01).结论 THP-1能够加速CTP诱导的BEAS-2B恶变,增加TNF-α的表达水平.%Objective To study the effects of monocyte-macrophages (THP-1) in malignant transformation of human bronchial epithelial cells (BEAS-2B) cells induced by coal tar pitch (CTP) and the expression of TNF-α in the process of the cell malignant transformation.Methods BEAS-2B cells and THP-1 Cells were divided into four groups:coal tar pitch (CTP) group,benzo(a)pyrene [B(a)P] group,dimethyl sulfoxide (DMSO) group,BEAS-2B and THP-1 co-culture (co-culture group) group.Carcinogenesis model was established.The soft agar colony formation,chromosome aberrations and cell cycle tests were used to detect the cellular malignant transformation.The ELISA

  6. Critical role of constitutive type I interferon response in bronchial epithelial cell to influenza infection.

    Directory of Open Access Journals (Sweden)

    Alan C-Y Hsu

    Full Text Available Innate antiviral responses in bronchial epithelial cells (BECs provide the first line of defense against respiratory viral infection and the effectiveness of this response is critically dependent on the type I interferons (IFNs. However the importance of the antiviral responses in BECs during influenza infection is not well understood. We profiled the innate immune response to infection with H3N2 and H5N1 virus using Calu-3 cells and primary BECs to model proximal airway cells. The susceptibility of BECs to influenza infection was not solely dependent on the sialic acid-bearing glycoprotein, and antiviral responses that occurred after viral endocytosis was more important in limiting viral replication. The early antiviral response and apoptosis correlated with the ability to limit viral replication. Both viruses reduced RIG-I associated antiviral responses and subsequent induction of IFN-β. However it was found that there was constitutive release of IFN-β by BECs and this was critical in inducing late antiviral signaling via type I IFN receptors, and was crucial in limiting viral infection. This study characterizes anti-influenza virus responses in airway epithelial cells and shows that constitutive IFN-β release plays a more important role in initiating protective late IFN-stimulated responses during human influenza infection in bronchial epithelial cells.

  7. TMEM16A mediates the hypersecretion of mucus induced by Interleukin-13.

    Science.gov (United States)

    Lin, Jiachen; Jiang, Youfan; Li, Li; Liu, Yanan; Tang, Hui; Jiang, Depeng

    2015-06-10

    Previous studies showed that the Ca(2+)-activated Cl(-) channel (CaCC) was involved in the pathogenesis of mucus hypersecretion induced by Interleukin-13 (IL-13). However, the mechanisms underlying the process were unknown. Recently, transmembrane protein 16A (TMEM16A) was identified as the channel underlying the CaCC current. The aim of the current study was to investigate whether the TMEM16A channel is part of the mechanism underlying IL-13-induced mucus hypersecretion. We observed that both TMEM16A mRNA and protein expression were significantly up-regulated after treatment with IL-13 in human bronchial epithelial 16 (HBE 16) cells, which correlated with an increase in mucus production. Additionally, mucus hypersecretion in rat airways was induced by intratracheal instillation of IL-13 and similar increases were observed in the expression of TMEM16A mRNA and protein in the bronchial epithelium. Niflumic acid (NA), a selective antagonist of CaCC, markedly blocked IL-13-induced mucin (MUC) 5AC mRNA and protein production in vivo and in vitro. Further investigation with HBE16 cells revealed that TMEM16A overexpression clearly promoted mucus production, IκBα phosphorylation, and p65 accumulation in the nucleus. The loss of TMEM16A resulted in inhibition of mucus production, and the TMEM16A-mediated production of MUC5AC was significantly blocked by a nuclear factor-kappa B (NF-κB) inhibitor. Therefore, the TMEM16A channel acts upstream of NF-κB in the regulation of mucus production. This is the first demonstration that the TMEM16A-NF-κB pathway is positively involved in IL-13-induced mucus production, which provides novel insight into the molecular mechanism of mucin overproduction.

  8. Sports in extreme conditions: the impact of exercise in cold temperatures on asthma and bronchial hyper-responsiveness in athletes.

    Science.gov (United States)

    Carlsen, Kai-Håkon

    2012-09-01

    Exercise-induced asthma (EIA) and bronchial hyper-responsiveness (BHR) are frequently reported among elite athletes of outdoor endurance winter sports, particularly in cross-country and biathlon skiers. The pathogenesis of EIA is related to water loss and heat-loss through the increased respiration during exercise, leading to mediator release, airways inflammation and increased parasympathetic nervous activity in the airways, causing bronchial constriction and BHR. In the competing elite athlete this is presently considered to be due to the frequently repeated increased ventilation during training and competitions in combination with the repeated environmental exposure to cold air in outdoor winter sports. It is important that athletes at risk of asthma and BHR are monitored through regular medical control with assessment of lung function and BHR, and when BHR or asthma is diagnosed, optimal controlling treatment through anti-inflammatory treatment by inhaled steroids should be started and relieving treatment (inhaled ipratropium bromide and inhaled β2-agonists) should be used to relieve bronchial constriction if present.

  9. Studies on bronchial hyperreactivity, allergic responsiveness, and asthma in rural and urban children of the highlands of Papua New Guinea.

    Science.gov (United States)

    Turner, K J; Dowse, G K; Stewart, G A; Alpers, M P

    1986-04-01

    The prevalence of asthma and allergic responsiveness in rural and urban children of the highlands of Papua New Guinea was studied. Bronchial provocation studies with histamine demonstrated significant bronchial hyperreactivity in 0.5% (1 in 195) rural and 1.7% (1 in 59) urban children, rates which were significantly lower than those observed in corresponding adult populations (7%). Urban children demonstrated a higher incidence of skin test reactivity toward Dermatophagoides pteronyssinus, Aspergillus fumigatus, and dog dander than did the rural children. However, there were no significant differences between these populations with regard to total serum IgE levels, the degree of parasitism as judged by stool examination, or allergic responses to Ascaris suum, plantain, and coffee bean husk. A more detailed study demonstrated age- and sex-related differences in total IgE and mite-specific RAST scores in the rural but not the urban population. These data suggest an active suppression of the capacity of children to mount an IgE response to environmental allergens such as the mite manifesting itself as low asthma prevalence. The data also indicate that, although the underlying defect of bronchial hyperreactivity in asthma may be genetically inherited, it is not revealed until the lung has received an allergen-induced inflammatory insult.

  10. Redox regulation of sperm surface thiols modulates adhesion to the fallopian tube epithelium.

    Science.gov (United States)

    Talevi, Riccardo; Zagami, Maria; Castaldo, Marianna; Gualtieri, Roberto

    2007-04-01

    Sperm that adhere to the fallopian tube epithelium are of superior quality and adhesion extends their fertile life. It has been postulated that periovulatory signals, as yet undefined, promote sperm release. In the in vitro studies described here, we examined the effects of several antioxidants, reportedly present within oviductal fluid, on the modulation of sperm-oviduct adhesion in bovine species. Results showed that 1) the cell-permeant thiols (penicillamine, beta mercaptoethanol, cysteine, and dithiotreitol), as well as the nonpermeant thiol, reduced glutathione, cause adhering spermatozoa to release from the epithelium; 2) thiol action is exerted on spermatozoa; and 3) oxidized glutathione, as well as the non-thiol antioxidants (dimethylthiourea, trolox, superoxide dismutase, and catalase) have no effect. Sperm surface sulfhydryls labeled with iodoacetamide fluorescein showed that spermatozoa devoid of sulfhydryls on the head surface adhered to the fallopian epithelium in vitro, whereas thiol-induced release increased the exposure of sulfhydryls on the sperm head surface. Finally, analysis of capacitation status demonstrated that uncapacitated spermatozoa adhered to the oviduct, and that thiol-induced release of spermatozoa was accompanied by capacitation. In conclusion, thiol-reducing agents in the oviductal fluid may modulate the redox status of sperm surface proteins, leading to the release of spermatozoa selected and stored through adhesion to the fallopian tube epithelium in the bovine species.

  11. Alternaria-induced release of IL-18 from damaged airway epithelial cells: an NF-κB dependent mechanism of Th2 differentiation?

    Directory of Open Access Journals (Sweden)

    Hiroki Murai

    Full Text Available BACKGROUND: A series of epidemiologic studies have identified the fungus Alternaria as a major risk factor for asthma. The airway epithelium plays a critical role in the pathogenesis of allergic asthma. These reports suggest that activated airway epithelial cells can produce cytokines such as IL-25, TSLP and IL-33 that induce Th2 phenotype. However the epithelium-derived products that mediate the pro-asthma effects of Alternaria are not well characterized. We hypothesized that exposure of the airway epithelium to Alternaria releasing cytokines that can induce Th2 differentiation. METHODOLOGY/PRINCIPAL FINDING: We used ELISA to measure human and mouse cytokines. Alternaria extract (ALT-E induced rapid release of IL-18, but not IL-4, IL-9, IL-13, IL-25, IL-33, or TSLP from cultured normal human bronchial epithelial cells; and in the BAL fluids of naïve mice after challenge with ALT-E. Both microscopic and FACS indicated that this release was associated with necrosis of epithelial cells. ALT-E induced much greater IL-18 release compared to 19 major outdoor allergens. Culture of naïve CD4 cells with rmIL-18 induced Th2 differentiation in the absence of IL-4 and STAT6, and this effect was abrogated by disrupting NF- κB p50 or with a NEMO binding peptide inhibitor. CONCLUSION/SIGNIFICANCE: Rapid and specific release of IL-18 from Alternaria-exposed damaged airway epithelial cells can directly initiate Th2 differentiation of naïve CD4(+ T-cells via a unique NF-κB dependent pathway.

  12. Effects of miR-200 family overexpression on migration of malignantly transformed human bronchial epithelial cells induced by α-particles%过表达miR-200家族对α粒子诱发恶性转化人支气管上皮细胞迁移能力的影响

    Institute of Scientific and Technical Information of China (English)

    高刚; 杨英杰; 刘建香; 田梅; 苏旭

    2013-01-01

    OBJECTIVE: To explore effects of miR-200 family overexpression on migration of malignantly transformed human bronchial epithelial cells (RHT35) induced by α-particles. METHODS:The mRNA and protein levels of ZEB family (ZEB1 and ZEB2) and epithelial-mesenchymal transition marker in RHT35 was measured by Real Time PCR and western blot 72 h after transfection of 100 nmol/L miR-200b mimic, miR-141 mimic or mimic control into RHT35 cells with SiPORT reagent. In vitro wound healing assay was used to investigate whether overexpression of miR- 200b and miR-141 could block migration of malignantly transformed cells induced by α-particles. RESULTS:The protein levels of ZEB1 and ZEB2 in RHT35 cells were upregulated compared with R15H20 and BEP2D cells. Overexpression of miR-200b and miR-141 led to reduced expression of ZEB1 and ZEB2 in RHT35 cells compared with mimic control (P<0.01). Overexpressions of miR-200b and miR-141 upregulated E-cad expression (P<0.05 or P<0.01) and downregulated N-cad expression in RHT35 cells (P<0.01). Overexpressions of miR-200b and miR-141 markedly blocked migration of RHT35 cells compared with mimic control. CONCLUSION:Overexpressions of miR-200b and miR-141 strongly block migration of RHT35 cells.%目的:探讨过表达miR-200家族对α粒子诱发恶性转化人支气管上皮细胞 (RHT35细胞)迁移能力的影响.方法:用SiPORT转染试剂转染100 nmol/L miR-200b mimic和miR-141 mimic或阴性对照 (mimic control)于RHT35细胞中72 h后,分别采用免疫印迹、实时荧光定量PCR技术检测过表达miR-200b和miR-141对 RHT35细胞ZEB家族 (ZEB1和ZEB2)及上皮间质转变相关标志分子表达的影响;并用伤口愈合实验研究过表达miR-200b和miR-141对RHT35细胞迁移能力的影响.结果:ZEB1和ZEB2蛋白在RHT35细胞中高表达.与阴性对照转染组相比,miR-200b mimic和miR-141 mimic转染组中miR-200靶基因ZEB家族表达显著下调(P<0.01);而上皮间质

  13. Effect of nitrogen dioxide on synthesis of inflammatory cytokines expressed by human bronchial epithelial cells in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Devalia, J.L.; Campbell, A.M.; Sapsford, R.J.; Rusznak, C.; Quint, D.; Godard, P.; Bousquet, J.; Davies, R.J. (St. Bartholomew' s Hospital, London (United Kingdom))

    1993-09-01

    Although studies of nitrogen dioxide (NO2) inhalation, in both animals and humans, have demonstrated that this agent can cause epithelial cell damage and inflammation of the airway epithelium, the mechanisms underlying these effects are not well understood. We have cultured human bronchial epithelial cells, as explant cultures from surgical tissue, and studied these firstly from their ability to constitutively synthesize specific proinflammatory cytokines and then investigated the effect of exposure to NO2 on the generation of these cytokines. Constitutive synthesis of cytokines was evaluated by analysis of both the expression of the mRNA for interleukin (IL)-1 beta, IL-4, IL-8, granulocyte/macrophage colony-stimulating factor (GM-CSF), tumor necrosis factor-alpha (TNF-alpha), and interferon-gamma (IFN-gamma), by the polymerase chain reaction (PCR), and by immunocytochemical staining for the presence of cell-associated IL-1 beta, IL-8, GM-CSF, TNF-alpha, and IFN-gamma, using specific monoclonal and polyclonal antibodies directed towards these cytokines. Release of IL-4, IL-8, GM-CSF, TNF-alpha, and IFN-gamma following exposure to 5% CO2 in air or 400 ppb and 800 ppb NO2 for 6 h was investigated by enzyme-linked immunosorbent assay. PCR demonstrated that the human bronchial epithelial cells expressed the mRNA for IL-1 beta, IL-8, GM-CSF, and TNF-alpha but not for IL-4 and IFN-gamma. Immunocytochemical staining confirmed the presence of endogenous IL-1 beta, IL-8, GM-CSF, and TNF-alpha.

  14. DIVALENT METAL TRANSPORTER-1 REGULATION BY IRON AND VANADIUM MODULATES HYDROGEN PEROXIDE-INDUCED DNA DAMAGE IN LUNG CELLS

    Science.gov (United States)

    The divalent metal transporter-1 (DMT1) participates in the detoxification of metals that can damage lung epithelium. Elevated iron levels increase the expression of DMT1 in bronchial epithelial cells stimulating its uptake and storage in ferritin, thus making iron unavailable t...

  15. STRUCTURAL PARTICULARITIES OF THE EPITHELIUM LINING THE LAMB EPIGLOTTIS

    Directory of Open Access Journals (Sweden)

    Vasile Rus

    2016-11-01

    Full Text Available Epiglottis presents a central axis covered by mucosa. The aim of this study was highlighting the type of epithelium lining the lamb epiglottis. Thus, we histologically processed the epiglottis from 3 lambs. The epithelium lining the whole epiglottis surface is non-keratinized stratified squamous, with different thickness from one side to the other. Hence, on the pharyngeal side the epithelium is twice as thick as the one found on the laryngeal side.

  16. CT findings of the patients with bronchial asthma

    Energy Technology Data Exchange (ETDEWEB)

    Katagiri, Shiro; Ohshima, Kazuki [Chiba-Tokusyukai Hospital, Funabashi (Japan); Ohsawa, Takehiko

    1996-06-01

    CT scans were obtained in 45 patients with bronchial asthma including 23 patients during asthmatic attack. CT findings were as follows. (1) In all cases, thickening of bronchial wall throughout from central to peripheral bronchi and without tapering and/or slight swelling of bronchovascular bundles were observed. (2) Characteristics findings in 23 patients with asthmatic attack, lobular and multilobular high attenuation area were observed in 17 patients (74%) and nonhomogeneous attenuation in lung fields were noticed in 13 patients (57%). (3) Multiple centrilobular sized high attenuation area were observed in 23 patients, but it was difficult to differenciation whether these findings were due to tiny nodules or to small vessels. In conclusion, further studies are needed to know which pathomorphological and/or pathophysiological conditions are underlying these CT findings. (author)

  17. Efficacy of naturopathy and yoga in bronchial asthma.

    Science.gov (United States)

    Rao, Y Chitharanjan; Kadam, Avinash; Jagannathan, Aarti; Babina, N; Rao, Raghavendra; Nagendra, Hongasandra Ramarao

    2014-01-01

    The aim of the study was to test the efficacy of a one month in-patient naturopathy and yoga programme for patients with asthma. Retrospective data of 159 bronchial asthma patients, undergoing the naturopathy and yoga programme, was analyzed for Forced Vital Capacity, Forced Expiratory Volume at the end of 1 second, Maximum Voluntary Ventilation and Peak Expiratory Flow Rate on admission, 11th day, on discharge and once in three months for three years. The paired sample t test results showed significant increase in the Forced Vital Capacity and Forced Expiratory Volume from the date of admission up to 6th month (P naturopathy and yoga for the management of bronchial asthma.

  18. Acid phosphatase and lipid peroxidation in human cataractous lens epithelium

    Directory of Open Access Journals (Sweden)

    Vasavada Abhay

    1993-01-01

    Full Text Available The anterior lens epithelial cells undergo a variety of degenerative and proliferative changes during cataract formation. Acid phosphatase is primarily responsible for tissue regeneration and tissue repair. The lipid hydroperoxides that are obtained by lipid peroxidation of polysaturated or unsaturated fatty acids bring about deterioration of biological membranes at cellular and tissue levels. Acid phosphatase and lipid peroxidation activities were studied on the lens epithelial cells of nuclear cataract, posterior subcapsular cataract, mature cataract, and mixed cataract. Of these, mature cataractous lens epithelium showed maximum activity for acid phosphatase (516.83 moles of p-nitrophenol released/g lens epithelium and maximum levels of lipid peroxidation (86.29 O.D./min/g lens epithelium. In contrast, mixed cataractous lens epithelium showed minimum activity of acid phosphatase (222.61 moles of p-nitrophenol released/g lens epithelium and minimum levels of lipid peroxidation (54.23 O.D./min/g lens epithelium. From our study, we correlated the maximum activity of acid phosphatase in mature cataractous lens epithelium with the increased areas of superimposed cells associated with the formation of mature cataract. Likewise, the maximum levels of lipid peroxidation in mature cataractous lens epithelium was correlated with increased permeability of the plasma membrane. Conversely, the minimum levels of lipid peroxidation in mixed cataractous lens epithelium makes us presume that factors other than lipid peroxidation may also account for the formation of mixed type of cataract.

  19. Sleeve resection for delayed presentation of traumatic bronchial transection.

    LENUS (Irish Health Repository)

    Mohamed, H Y

    2010-02-01

    Tracheobronchial disruption is uncommon in blunt chest trauma. Many of these patients die before reaching the hospital. In the majority of survivors diagnosis is occasionally delayed resulting in complications like airway stenosis and lung collapse. Thus it is important to have radiological follow up after severe thoracic trauma. Sleeve resection can be an excellent option to conserve lung tissue in delayed presentation of bronchial transection.

  20. Modulation of the Cholinergic Mechanisms in the Bronchial Smooth Muscle.

    Science.gov (United States)

    1984-06-01

    Ginsborg and Hirst, 1q72; Sawynok and Jhamandas, 1976), although theopylline has not shown to be a specific adenosine receptor antagonist in all the tissues... theopylline and other cyclic nucletide phosphodiesterase inhibitors. Acta Pharmacol. Toxicol. 45, 336-344. Fredholm, B.B. and P. Hedqvist, 1980...51 mM) evoked release of [3H]-Ach from cholinergic nerves in the bronchial smooth muscle. The effect of theopylline (I mM) on the response to

  1. Temperament and stress coping styles in bronchial asthma patients

    Science.gov (United States)

    Kuna, Piotr; Witusik, Andrzej; Wujcik, Radosław; Antczak, Adam; Pietras, Tadeusz

    2016-01-01

    Introduction Temperament, defined as the formal characteristics of behavior, is a personality trait which can influence the clinical presentation and course of bronchial asthma. It determines susceptibility to stress as well as stress coping styles. Aim The aim of the study was to assess whether healthy subjects differ from bronchial asthma patients with regard to temperamental variables and stress coping styles, and whether these factors may also differentiate patients with severe asthma from those with the milder form. The study also assesses whether the results of flow volume curve analysis correlate with temperamental traits and stress coping styles. Material and methods The study was conducted in a group of 65 asthma patients and 62 healthy controls. All underwent flow volume curve examination and psychological tests: Formal Characteristics of Behavior – Temperament Inventory (FCB-TI) and Coping in Stress Situations (CISS) questionnaire. Results Bronchial asthma patients were characterized by a lower level of briskness (“agility”) than healthy subjects (13.35 ±4.48 vs. 14.97 ±3.98, p = 0.031). The remaining temperamental traits and stress coping styles did not differ between the groups. Additionally, the forced expiratory volume in 1 s (FEV1) value was found to correlate negatively with the intensity of the emotion-oriented stress coping style, whereas FEV1 and forced vital capacity (FVC) were found to positively correlate with briskness, emotional reactivity and endurance, while a negative correlation was found with activity. Conclusions Briskness differentiates healthy subjects from bronchial asthma patients. The values obtained in FEV1 and FVC pulmonary function tests were also found to correlate with some temperamental variables. PMID:28035226

  2. Use motion games in exercise with children with bronchial asthma

    Directory of Open Access Journals (Sweden)

    Viktoriya Polkovnyk-Markova

    2016-02-01

    Full Text Available Purpose: to analyze the possibility of using moving games in the rehabilitation of children with bronchial asthma. Material & Methods: the modern scientific literature on integrated prevention and treatment of children with asthma. Results: A high frequency of morphological and functional deviations at children with asthma. Classification and examples of mobile games, which can be used for this group of children. Conclusions: the results of modern research that show the effectiveness the use of physical rehabilitation, including moving games.

  3. Aeroallergen sensitivity among patients suffering from bronchial asthma in Bangalore

    Directory of Open Access Journals (Sweden)

    Giriyanna Gowda

    2013-01-01

    Full Text Available Background: Asthma is a serious public health problem throughout the world and its prevalence has increased in last 2-3 decades. Allergens are one of the many factors which trigger an attack of asthma. Skin prick test is useful in identifying the offending allergen in bronchial asthma. Aim: To identify the possible offending allergens in patients of bronchial asthma. Materials and Methods: The study was a descriptive study conducted at allergy center, Kempegowda Institute of Medical Sciences Hospital and Research Center, Bangalore from January to December 2011. Skin prick test was done in 139 patients suffering from bronchial asthma using 49 allergens extracts. Statistical Analysis: Frequency, proportions, Chi-square test, odds ratio, and 95% confidence interval was used. Results: Out of 139 patients who underwent the skin prick tests, 40% (56 were males and 60% (83 were females. Majority, that is, 60% were in the age group of 21-40 years. Forty-three percent (60 had family history of asthma/atopy, 80% (111 had allergic rhinitis, 24% (34 had chronic urticaria, and 24% (33 had allergic conjunctivitis. Out of 139 patients, 100 (71.94% were sensitive for one or more allergens. The common offending allergens found in the study were dust mites (Dermatophagoides farinae and D. pteronyssinus (DF and DP - 49.28%, dusts - 7.2%, pollens - 6.77%, insects - 6.62%, fungi - 4.53%, and epithelia - 1.92%. Conclusion: The most common allergens in bronchial asthma were dust mites followed by dusts and pollens. Identifying possible allergens in asthma patients help in allergen avoidance and immunotherapy in these patients.

  4. Upper respiratory tract disease and bronchial asthma

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    2009186 The clinical significance of noninvasive inflammatory markers in exhaled breath condensate and induced sputum in persistent asthmatic patients. TAN Chengwu(谭成戊),et al.Dept Respir Med,West China Hosp,Sichuan Univ,Chengdu,Sichuan 610041.Chin J Interm Med,2009;48(4):299-303.

  5. Efficient replication of the novel human betacoronavirus EMC on primary human epithelium highlights its zoonotic potential.

    Science.gov (United States)

    Kindler, Eveline; Jónsdóttir, Hulda R; Muth, Doreen; Hamming, Ole J; Hartmann, Rune; Rodriguez, Regulo; Geffers, Robert; Fouchier, Ron A M; Drosten, Christian; Müller, Marcel A; Dijkman, Ronald; Thiel, Volker

    2013-02-19

    barrier against invading respiratory pathogens is the epithelium, representing the entry point and primary target tissue of respiratory viruses. We show that human bronchial epithelia are highly susceptible to HCoV-EMC infection. Furthermore, HCoV-EMC, like other coronaviruses, evades innate immune recognition, reflected by the lack of interferon and minimal inflammatory cytokine expression following infection. Importantly, type I and type III interferon treatment can efficiently reduce HCoV-EMC replication in the human airway epithelium, providing a possible avenue for treatment of emerging virus infections.

  6. Bicarbonate exporting transporters in the ovine ruminal epithelium.

    Science.gov (United States)

    Bilk, S; Huhn, K; Honscha, K U; Pfannkuche, H; Gäbel, G

    2005-07-01

    In order to stabilize the intraruminal pH, bicarbonate secretion by the ruminal epithelium seems to be an important prerequisite. The present study therefore focussed on the characterization of bicarbonate exporting systems in ruminal epithelial cells. Intracellular pH (pH(i)) was measured spectrofluorometrically in primary cultured ruminal epithelial cells loaded with the pH-sensitive fluorescent dye, 2,7-bis(carboxyethyl)-5(6')-carboxyfluorescein acetomethyl ester. Switching from CO2/HCO3- -buffered to HEPES-buffered solution caused a rapid intracellular alkalinization followed by a counter-regulation towards initial pH(i). The recovery of pH(i) was dependent upon extracellular chloride, but independent of extracellular sodium. Adding 500 microM H2DIDS significantly reduced the increase of pH(i). For further characterization of the bicarbonate exporting systems, we tested the ability to reverse the direction from HCO3- export to import in the absence of sodium and chloride. Under sodium and chloride-free conditions, counter-regulation after CO2-induced pH(i) decrease did not differ from pH(i) recovery in the presence of sodium and chloride. Existence of bicarbonate exporting systems in cultured ruminal epithelial cells and intact ruminal epithelium was verified by reverse transcription polymerase chain reaction (RT-PCR). Using RT-PCR and subsequent sequencing, expression of mRNA encoding for AE2, DRA and PAT1 could be found. Bicarbonate exporting systems could therefore be detected both on the functional and structural level.

  7. Orbital Cellulitis: A Rare Presentation of Metastatic Bronchial Carcinoma

    Directory of Open Access Journals (Sweden)

    Rohit Kumar

    2011-01-01

    Full Text Available Objective. We report a rare and unusual case of bronchial carcinoma presenting with symptoms of complications of sinonasal disease. Case Report. A 66-year-old lady was referred with a 1-week history of progressive ocular pain, chemosis, and visual disturbance. Computed tomography of the paranasal sinuses revealed frontal and ethmoidal sinus opacification with orbital involvement consistent with a diagnosis of orbital cellulitis secondary to sinusitis. Surgical exploration revealed that the sinuses and right orbit were filled with soft tissue and subsequent histopathological examination of the biopsies indicating metastases from an adenosquamous bronchial carcinoma. Further imaging revealed a large, asymptomatic, bronchial primary with deposits in the brain and liver. The advanced presentation of the disease limited treatment to best supportive care. Conclusion. Orbital cellulitis and sinonasal malignancies have a similar pattern of clinical presentation, posing a potential diagnostic pitfall. There are only two previously reported cases of metastatic lung carcinoma in the frontal sinus with 15 cases of sinonasal tract involvement reported overall. There are no reported cases of adenosquamous carcinoma in the sinonasal tract.

  8. SURGICAL TREATMENT AND PROGNOSIS OF BRONCHIAL CARCINOID TUMOR

    Institute of Scientific and Technical Information of China (English)

    张志庸; 李单青; 戈烽; 李泽坚; 孙成孚; 徐乐天; 张士农

    1996-01-01

    In order to understand the effect of surgery in the treatment of the bronchial carcinoid tumor and thefactors affecting prognosis, 18 cases of bronchial carcinoid tumor are presented, including 5 cases withCushing's syndiome. There were Iobectoray in 10, lung wedge resection in 3, excision of intraluminal tumor of bronchus in 3, exploratory thoracotomy in 2 cases.No operation death.Pathological examinstion revealed 14 cases were typical carcinoid tumor and 4 cases were atypical carcinoid tumor.By 2-13 years fol-low-up,3,5 and 10 years survival rate were 82%,78% and 70% respectively.Bronchial carcinoid tumor is often confused microscopic and immunohistochemistry studies.Those patients accompanied with ectopicACTH secretion always have Cushing''s syndrome,resection of tumor can produce good result.Proper operation method depnds on the location of the tumor and patient''s extent of cardiac and pulmonary peserve.Atypical carcinoid tumor had high malignancy and poor prognosis.The size of tumor,lymph node involve ment and adjuvant therapy seem no definite effect on the patients'' survival rate.

  9. Dermal and bronchial hyperreactivity in urticarial dermographism and urticaria factitia.

    Science.gov (United States)

    Henz, B M; Jeep, S; Ziegert, F S; Niemann, J; Kunkel, G

    1996-03-01

    For investigation of a possible relationship between cutaneous and bronchial hyperreactivity, 74 subjects were grouped according to the presence (n = 33) or absence (n = 41) of urticarial dermographism after application of a standardized shearing pressure with a dermographometer (12.7 x 10(5) Pa). the two groups did not differ in age, sex, smoking habits, presence of urticaria and atopy, or serum IgE levels. Erythema of the dermographic test sites was always significantly greater (P dermographism at 2, 4, and 8 min, and cutaneous reactivity with titrated prick tests was significantly increased in this group with low concentrations of histamine, 0.01% and substance P (0.25 mM) (P dermographism, exhibited bronchial hyperreactivity. However, significantly more subjects with urticarial dermographism had an increase in airway resistance and a decrease in specific airway conductance (P dermographism (urticaria factitia), these differences were even more significant (P < 0.001). These subjects also had larger skin test reactions and significantly higher IgE levels (P < 0.01). Thus, the present data show an association, which may be based on common mechanisms of allergic inflammation, between cutaneous and bronchial hyperreactivity.

  10. A light, transmission and scanning electron microscope study of snuff-treated hamster cheek pouch epithelium.

    Science.gov (United States)

    Ashrafi, S H; Das, A; Worowongvasu, R; Mehdinejad, B; Waterhouse, J P

    1992-03-01

    The effects of smokeless tobacco (snuff) on hamster cheek mucosa were studied by light microscopy, transmission (TEM) and scanning electron microscopy (SEM). Two grams of commercially available smokeless tobacco were placed into the blind end of the right cheek pouch of each experimental animal, once a day and five days a week for 24 months. The control animals did not receive smokeless tobacco. After 24 months treatment with smokeless tobacco, hamster cheek mucosal epithelium lost its translucency and had become whitish in color. By light microscopy hyperorthokeratosis, prominent granular cell layers with increased keratohyalin granules and hyperplasia were seen. At the ultrastructural level, wider intercellular spaces filled with microvilli, numerous shorter desmosomes, many thin tonofilament bundles, increased number of mitochondria, membrane coating granules and keratohyalin granules were seen in snuff-treated epithelium. The changes in the surface of the epithelium as seen by SEM were the development of an irregular arrangement of the microridges and the disappearance of the normal honeycomb pattern. The microridges were irregular, widened and surrounded the irregular elongated pits. Some smooth areas without microridges and pits were also seen. The long-term histological, TEM and SEM changes induced by smokeless tobacco treatment of the epithelium are well correlated with each other and were similar to those reported in human leukoplakia without dyskeratosis. They imply changes of pathological response resulting from topically applied snuff.

  11. A quantitative ultrastructural analysis of changes in hamster cheek-pouch epithelium treated with vitamin A.

    Science.gov (United States)

    Hill, M W; Harris, R R; Carron, C P

    1982-01-01

    The ultrastructural changes induced by the topical application of retinol acetate on hamster cheek pouch epithelium were evaluated using stereological analysis. Electron micrographs were prepared of the basal and superficial regions of the nucleated cell layer of the epithelium obtained from 3 treated and 3 control animals and examined at two levels of magnification. A total of 528 micrographs were analyzed using a coherent double lattice test system. Although the mean thickness of the nucleated cell layer did not change significantly after 10 days of treatment with retinol acetate the formation of keratinized squames was completely inhibited. This was paralleled by significant changes in the volume density of a number of organelles in both the basal and superficial strata. Rough endoplasmic reticulum increased significantly whereas filaments, which maintained a constant diameter of approximately 9 nm, keratohyalin granules and membrane-coating granules decreased in both strata. Desmosomes also showed a significant decrease in numerical area density in the treated tissues. In contrast, no changes were observed in the volume density of the Golgi apparatus, free ribosomes or mitochondria in the treated epithelium. It is concluded that this treatment provides an epithelium lacking all features of keratinization and may be a useful model for examining metabolic activities specifically associated with keratinization.

  12. Expression of the stem cell marker, SOX2, in ameloblastoma and dental epithelium.

    Science.gov (United States)

    Juuri, Emma; Isaksson, Sanna; Jussila, Maria; Heikinheimo, Kristiina; Thesleff, Irma

    2013-12-01

    Ameloblastomas are locally invasive odontogenic tumors that exhibit a high rate of recurrence and often associate with the third molars. They are suggested to originate from dental epithelium because the tumor cells resemble epithelial cells of developing teeth. Expression of the transcription factor SOX2 has been previously localized in epithelial stem and progenitor cells in developing teeth as well as in various tumors. Here, we show that SOX2 is expressed in the epithelial cells of follicular and plexiform ameloblastomas. SOX2 was localized in the dental lamina of developing human primary molars. It was also expressed in the fragmented dental lamina associated with the third molars and in the epithelium budding from its posterior aspect in mice. However, no SOX2 expression was detected in either Hertwig's epithelial root sheath directing the formation of roots or in the epithelial cell rests of Malassez covering the completed roots. SOX2 was associated with supernumerary tooth formation in odontoma-like tumors induced by Wnt signal activation in mice. We propose that SOX2 functions in maintaining the progenitor state of epithelium in ameloblastomas and that ameloblastomas may originate from SOX2-expressing dental lamina epithelium.

  13. Apico-basal forces exerted by apoptotic cells drive epithelium folding.

    Science.gov (United States)

    Monier, Bruno; Gettings, Melanie; Gay, Guillaume; Mangeat, Thomas; Schott, Sonia; Guarner, Ana; Suzanne, Magali

    2015-02-12

    Epithelium folding is a basic morphogenetic event that is essential in transforming simple two-dimensional epithelial sheets into three-dimensional structures in both vertebrates and invertebrates. Folding has been shown to rely on apical constriction. The resulting cell-shape changes depend either on adherens junction basal shift or on a redistribution of myosin II, which could be driven by mechanical signals. Yet the initial cellular mechanisms that trigger and coordinate cell remodelling remain largely unknown. Here we unravel the active role of apoptotic cells in initiating morphogenesis, thus revealing a novel mechanism of epithelium folding. We show that, in a live developing tissue, apoptotic cells exert a transient pulling force upon the apical surface of the epithelium through a highly dynamic apico-basal myosin II cable. The apoptotic cells then induce a non-autonomous increase in tissue tension together with cortical myosin II apical stabilization in the surrounding tissue, eventually resulting in epithelium folding. Together our results, supported by a theoretical biophysical three-dimensional model, identify an apoptotic myosin-II-dependent signal as the initial signal leading to cell reorganization and tissue folding. This work further reveals that, far from being passively eliminated as generally assumed (for example, during digit individualization), apoptotic cells actively influence their surroundings and trigger tissue remodelling through regulation of tissue tension.

  14. Brain-derived neurotrophic factor (BDNF) expression in normal and regenerating olfactory epithelium of Xenopus laevis.

    Science.gov (United States)

    Frontera, Jimena Laura; Cervino, Ailen Soledad; Jungblut, Lucas David; Paz, Dante Agustín

    2015-03-01

    Olfactory epithelium has the capability to continuously regenerate olfactory receptor neurons throughout life. Adult neurogenesis results from proliferation and differentiation of neural stem cells, and consequently, olfactory neuroepithelium offers an excellent opportunity to study neural regeneration and the factors involved in the maintenance and regeneration of all their cell types. We analyzed the expression of BDNF in the olfactory system under normal physiological conditions as well as during a massive regeneration induced by chemical destruction of the olfactory epithelium in Xenopus laevis larvae. We described the expression and presence of BDNF in the olfactory epithelium and bulb. In normal physiological conditions, sustentacular (glial) cells and a few scattered basal (stem) cells express BDNF in the olfactory epithelium as well as the granular cells in the olfactory bulb. Moreover, during massive regeneration, we demonstrated a drastic increase in basal cells expressing BDNF as well as an increase in BDNF in the olfactory bulb and nerve. Together these results suggest an important role of BDNF in the maintenance and regeneration of the olfactory system.

  15. Blood Level of Polymorphonuclear Neutrophil Leukocytes and Bronchial Hyperreactivity in Chronic Obstructive Pulmonary Disease

    OpenAIRE

    Cukic, Vesna

    2015-01-01

    Introduction: Polymorphonuclear neutrophil leukocytes (PMNL) have an important defensive role against various microorganisms and other agents, but by liberating various substances, first of all the superoxide anion (O 2¯), they can damage the bronchial mucosa and influence the development of bronchial inflammation which is the fundamental of bronchial hyperreactivity (BHR). Objective: to show the role of the PMNL for development and level of BHR in patients with chronic obstructive pulmonary ...

  16. Alterations of FHIT Gene and P16 Gene in Nickel Transformed Human Bronchial Epithelial Cells

    Institute of Scientific and Technical Information of China (English)

    WEI-DONG JI; JIA-KUN CHEN; JIA-CHUN LU; ZHONG-LIANG WU; FEI YI; SU-MEI FENG

    2006-01-01

    To study the alterations of FHIT gene and P16 gene in malignant transformed human bronchial epithelial cells induced by crystalline nickel sulfide using an immoral human bronchial epithelial cell line, and to explore the molecular mechanism of nickel carcinogenesis. Methods 16HBE cells were treated 6 times with different concentrations of NiS in vitro, and the degree of malignant transformation was determined by assaying the anchorage-independent growth and tumorigenicity. Malignant transformed cells and tumorigenic cells were examined for alterations of FHIT gene and P16 gene using RT-PCR, DNA sequencing, silver staining PCR-SSCP and Western blotting. Results NiS-treated cells exhibited overlapping growth. Compared with that of negative control cells, soft agar colony formation efficiency of NiS-treated cells showed significant increases (P<0.01) and dose-dependent effects. NiS-treated cells could form tumors in nude mice, and a squamous cell carcinoma was confirmed by histopathological examination. No mutation of exon 2 and exons 2-3, no abnormal expression in p16 gene and mutation of FHIT exons 5-8 and exons 1-4 or exons 5-9 were observed in transformed cells and tumorigenic cells. However, aberrant transcripts or loss of expression of the FHIT gene and Fhit protein was observed in transformed cells and tumorigenic cells. One of the aberrant transcripts in the FHIT gene was confirmed to have a deletion of exon 6, exon 7, exon 8, and an insertion of a 36 bp sequence replacing exon 6-8. Conclusions The FHIT gene rather than the P16 gene, plays a definite role in nickel carcinogenesis. Alterations of the FHIT gene induced by crystalline NiS may be a molecular event associated with carcinogen, chromosome fragile site instability and cell malignant transformation. FHIT may be an important target gene activated by nickel and other exotic carcinogens.

  17. E-Cigarette Affects the Metabolome of Primary Normal Human Bronchial Epithelial Cells.

    Directory of Open Access Journals (Sweden)

    Argo Aug

    Full Text Available E-cigarettes are widely believed to be safer than conventional cigarettes and have been even suggested as aids for smoking cessation. However, while reasonable with some regards, this judgment is not yet supported by adequate biomedical research data. Since bronchial epithelial cells are the immediate target of inhaled toxicants, we hypothesized that exposure to e-cigarettes may affect the metabolome of human bronchial epithelial cells (HBEC and that the changes are, at least in part, induced by oxidant-driven mechanisms. Therefore, we evaluated the effect of e-cigarette liquid (ECL on the metabolome of HBEC and examined the potency of antioxidants to protect the cells. We assessed the changes of the intracellular metabolome upon treatment with ECL in comparison of the effect of cigarette smoke condensate (CSC with mass spectrometry and principal component analysis on air-liquid interface model of normal HBEC. Thereafter, we evaluated the capability of the novel antioxidant tetrapeptide O-methyl-l-tyrosinyl-γ-l-glutamyl-l-cysteinylglycine (UPF1 to attenuate the effect of ECL. ECL caused a significant shift in the metabolome that gradually gained its maximum by the 5th hour and receded by the 7th hour. A second alteration followed at the 13th hour. Treatment with CSC caused a significant initial shift already by the 1st hour. ECL, but not CSC, significantly increased the concentrations of arginine, histidine, and xanthine. ECL, in parallel with CSC, increased the content of adenosine diphosphate and decreased that of three lipid species from the phosphatidylcholine family. UPF1 partially counteracted the ECL-induced deviations, UPF1's maximum effect occurred at the 5th hour. The data support our hypothesis that ECL profoundly alters the metabolome of HBEC in a manner, which is comparable and partially overlapping with the effect of CSC. Hence, our results do not support the concept of harmlessness of e-cigarettes.

  18. Retinal Pigment Epithelium and Müller Progenitor Cell Interaction Increase Müller Progenitor Cell Expression of PDGFR and Ability to Induce Proliferative Vitreoretinopathy in a Rabbit Model

    Directory of Open Access Journals (Sweden)

    Gisela Velez

    2012-01-01

    Full Text Available Purpose. Proliferative vitreoretinopathy (PVR is a complication of retinal detachment characterized by redetachment of the retina as a result of membrane formation and contraction. A variety of retinal cells, including retinal pigment epithelial (RPE and Müller glia, and growth factors may be responsible. Platelet-derived growth factor receptor alpha (PDGFRα is found in large quantities in PVR membranes, and is intrinsic to the development of PVR in rabbit models. This study explores the expression of PDGFR in cocultures of RPE and Müller cells over time to examine how these two cell types may collaborate in the development of PVR. We also examine how changes in PDGFRα expression alter Müller cell pathogenicity. Methods. Human MIO-M1 Müller progenitor (MPC and ARPE19 cells were studied in a transmembrane coculture system. Immunocytochemistry and Western blot were used to look at PDGFRα, PDGFRβ, and GFAP expression. A transfected MPC line cell line expressing the PDGFRα (MIO-M1α was generated, and tested in a rabbit model for its ability to induce PVR. Results. The expression of PDGFRα and PDGFRβ was upregulated in MIO-M1 MPCs cocultured with ARPE19 cells; GFAP was slightly decreased. Increased expression of PDGFRα in the MIO-M1 cell line resulted in increased pathogenicity and enhanced ability to induce PVR in a rabbit model. Conclusions. Müller and RPE cell interaction can lead to upregulation of PDGFRα and increased Müller cell pathogenicity. Müller cells may play a more active role than previously thought in the development of PVR membranes, particularly when stimulated by an RPE-cell-rich environment. Additional studies of human samples and in animal models are warranted.

  19. Radiation response of the mouse tongue epithelium

    Energy Technology Data Exchange (ETDEWEB)

    Moses, R.; Kummermehr, J.

    1986-01-01

    Mouse tongue mucosa has been used as a model to study dose responses to local irradiation. Although the irradiation procedures is less feasible and more time-consuming than e.g. snout irradiation, the tongue is the only location where a reasonable area of intraoral, multilayered epithelium in the mouse can be locally treated and scored, and a relatively small burden is imposed on the animal. In pilot experiments with external 300 kV x-irradiation just tolerated by the lip, the authors did not see critical damage to the tongue. In the present model, the onset of denudation was not correctly predicted by the normal turnover time of the tissue.

  20. Characterization of FGF family growth factors concerning branching morphogenesis of mouse lung epithelium.

    Science.gov (United States)

    Goto, Asami; Yamazaki, Naohiro; Nogawa, Hiroyuki

    2014-05-01

    Mouse lung rudiments express eight members of fibroblast growth factor (FGF) family genes from embryonic day 10 (E10) to E13. Some of these are expressed in either the epithelium or mesenchyme, while others are expressed in both. Incorporating the results of our previous study, we characterized the branch-inducing activities of all of FGFs expressed in the early lung rudiment. Of these, FGF1, FGF2, FGF7, FGF9 and FGF10 induced branching morphogenesis in Matrigel-embedded E11 epithelium, and their effective concentrations varied (10 nM, 10 nM, 3 nM, 1 nM, and 100 nM, respectively). Whereas shaking culture dishes containing medium supplemented with FGF7 or FGF10 showed reduced branching morphogenesis, those supplemented with FGF1, FGF2, or FGF9 did not, suggesting the involvement of autocrine growth factor(s) in branching morphogenesis induced by FGF7 or FGF10. In the presence of heparin, a well-known activator of FGF signaling, cystic morphology with lumen expansion was observed in cultures containing FGF1, FGF7, or FGF10, but growth arrest was observed in cultures containing FGF2 or FGF9. These results indicate that several paracrine and autocrine FGFs function during branching morphogenesis of lung epithelium.

  1. Challenges and opportunities for tissue-engineering polarized epithelium.

    Science.gov (United States)

    Paz, Ana C; Soleas, John; Poon, James C H; Trieu, Dennis; Waddell, Thomas K; McGuigan, Alison P

    2014-02-01

    The epithelium is one of the most important tissue types in the body and the specific organization of the epithelial cells in these tissues is important for achieving appropriate function. Since many tissues contain an epithelial component, engineering functional epithelium and understanding the factors that control epithelial maturation and organization are important for generating whole artificial organ replacements. Furthermore, disruption of the cellular organization leads to tissue malfunction and disease; therefore, engineered epithelium could provide a valuable in vitro model to study disease phenotypes. Despite the importance of epithelial tissues, a surprisingly limited amount of effort has been focused on organizing epithelial cells into artificial polarized epithelium with an appropriate structure that resembles that seen in vivo. In this review, we provide an overview of epithelial tissue organization and highlight the importance of cell polarization to achieve appropriate epithelium function. We next describe the in vitro models that exist to create polarized epithelium and summarize attempts to engineer artificial epithelium for clinical use. Finally, we highlight the opportunities that exist to translate strategies from tissue engineering other tissues to generate polarized epithelium with a functional structure.

  2. [The new era of epithelium-targeted drug development].

    Science.gov (United States)

    Shimizu, Yoshimi; Nagase, Shotaro; Yagi, Kiyohito; Kondoh, Masuo

    2014-01-01

    Epithelium plays pivotal roles in biological barrier separating the inside of body and the outside environment. Ninety percent of malignant tumors are derived from epithelium. Most pathological microorganisms invade into the body from mucosal epithelium. Thus, epithelium is potential targets for drug development. Claudins (CLs), a family of tetra-transmembrane protein consisting of over 20 members, are structural and functional components of tight junction-seals in epithelium. Modulation of CL-seals enhanced mucosal absorption of drugs. CLs are often over-expressed in malignant tumors. CL-4 expression is increased in the epithelial cells covering the mucosal immune tissues. Very recently, CLs are also expected to be targets for traumatic brain injury and regenerative therapy. In this review, we overview the past, the present and the future of CLs-targeted drug development.

  3. Proteasome inhibitor MG-132 regulates the expression of VEGF in human bronchial epithelial cell line, BEAS-2B

    Institute of Scientific and Technical Information of China (English)

    Xuefan Cui; Kaisheng Yin; Mao Huang; Linfu Zhou

    2005-01-01

    Objective: To explore the effects of MG-132 on the expression of VEGF in bronchial epithelial cell line, BEAS2B. Methods: Semi-quantitive RT-PCR for VEGF mRNA and enzyme-linked immunosorbent assay (ELISA) for VEGF protein were performed. Results: MG-132 increased the expression of VEGF mRNA and protein BEAS-2B cells in time-and concentration-dependent manners. After 24-h stimulation, 25 μmol/L MG-132 increased the maximal levels of VEGF protein in cell-conditioned medium. When the cells were stimulated with cycloheximide(CHX) before treatment with MG-132, the MG-132-induced production of VEGF protein was inhibited compared to the unstimulated cells. Supernatant of condition-medium treatment with MG-132 enhanced the growth of HUVEC.Conclusion: MG-132 induces VEGF gene expression in human bronchial epithelial cells line, BEAS-2B, and the MG-132-induced expression of VEGF may modulate lung tissue injury due to airway inflammation.

  4. Intestinal epithelium is more susceptible to cytopathic injury and altered permeability than the lung epithelium in the context of acute sepsis.

    Science.gov (United States)

    Julian, Mark W; Bao, Shengying; Knoell, Daren L; Fahy, Ruairi J; Shao, Guohong; Crouser, Elliott D

    2011-10-01

    Mitochondrial morphology and function are altered in intestinal epithelia during endotoxemia. However, it is unclear whether mitochondrial abnormalities occur in lung epithelial cells during acute sepsis or whether mitochondrial dysfunction corresponds with altered epithelial barrier function. Thus, we hypothesized that the intestinal epithelium is more susceptible to mitochondrial injury than the lung epithelium during acute sepsis and that mitochondrial dysfunction precedes impaired barrier function. Using a resuscitated feline model of Escherichia coli-induced sepsis, lung and ileal tissues were harvested after 6 h for histological and mitochondrial ultrastructural analyses in septic (n = 6) and time-matched controls (n = 6). Human lung epithelial cells (HLEC) and Caco-2 monolayers (n = 5) were exposed to 'cytomix' (TNFα: 40 ng/ml, IL-1β: 20 ng/ml, IFNγ: 10 ng/ml) for 24-72 h, and measurements of transepithelial electrical resistance (TER), epithelial permeability and mitochondrial membrane potential (ΔΨ) were taken. Lung epithelial morphology, mitochondrial ultrastructure and pulmonary gas exchange were unaltered in septic animals compared to matching controls. While histologically intact, ileal epithelia demonstrated marked mitochondrial ultrastructural damage during sepsis. Caco-2 monolayers treated with cytomix showed a significant decrease in mitochondrial ΔΨ within 24 h, which was associated with a progressive reduction in TER and increased epithelial permeability over the subsequent 48 h. In contrast, mitochondrial ΔΨ and epithelial barrier functions were preserved in HLEC following cytomix. These findings indicate that intestinal epithelium is more susceptible to mitochondrial damage and dysfunction than the lung epithelium in the context of sepsis. Early alterations in mitochondrial function portend subsequent epithelial barrier dysfunction.

  5. Sleep Disorders in Patients with Bronchial Asthma

    Science.gov (United States)

    Cukic, Vesna; Lovre, Vladimir; Dragisic, Dejan

    2011-01-01

    Respiratory disturbances during sleep are recognized as extremely common disorders with important clinical consequences. Breathing disorders during sleep can result in broad range of clinical manifestations, the most prevalent of which are unrefreshing sleep, daytime sleepiness and fatigue, and cognitive impairmant. There is also evidence that respiratory-related sleep disturbances can contribute to several common cardiovascular and metabolic disorders, including systemic hypertension, cardiac dysfunction, and insulin-resistance. Correlations are found between asthma-related symptoms and sleep disturbances. Difficulties inducing sleep, sleep fragmentation on polysomnography, early morning awakenings and daytime sleepiness are more common in asthmatics compared with subjects without asthma. The “morning deep” in asthma is relevant for the characterization of asthma severity, and impact drugs’ choices. Sleep and night control of asthma could be relevant to evaluate disease’s control. Appropriate asthma control recovering is guarantor for better sleep quality in these patients and less clinical consequences of respiratory disturbances during sleep. PMID:23678304

  6. The Role of Eosinophilic Cationic Proteins, Total IgE and Eosinophilia in Children with Bronchial Hyperresponsiveness

    Directory of Open Access Journals (Sweden)

    Ungureanu Adina

    2016-11-01

    Full Text Available Bronchial hyperreactivity (HRB, is defined as an excessive bronchial constriction that acts as an exaggerated bronchoconstrictor of the airways. This occurs as a secondary action of a nonspecific stimuli.

  7. Detection of Bronchial Function of NHBD Lung Following One-h Warm Ischemia by Organ Bath Model

    Institute of Scientific and Technical Information of China (English)

    Yang YANG; Song ZHAO; Qiuming LIAO; Jianjun WANG

    2009-01-01

    laxant abilities of bronchial smooth muscles, and the epithe-lium-dependent adjustment both kept intact. Organ bath model could be a liable and scientific way to evaluate the bronchial function of NHBD lung.

  8. File list: Unc.Oth.05.AllAg.Olfactory_epithelium [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Unc.Oth.05.AllAg.Olfactory_epithelium mm9 Unclassified Others Olfactory epithelium ...SRX112960 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Unc.Oth.05.AllAg.Olfactory_epithelium.bed ...

  9. File list: Unc.Oth.20.AllAg.Olfactory_epithelium [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Unc.Oth.20.AllAg.Olfactory_epithelium mm9 Unclassified Others Olfactory epithelium ...SRX112960 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Unc.Oth.20.AllAg.Olfactory_epithelium.bed ...

  10. File list: Unc.Oth.50.AllAg.Olfactory_epithelium [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Unc.Oth.50.AllAg.Olfactory_epithelium mm9 Unclassified Others Olfactory epithelium ...SRX112960 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Unc.Oth.50.AllAg.Olfactory_epithelium.bed ...

  11. File list: Unc.Oth.10.AllAg.Olfactory_epithelium [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Unc.Oth.10.AllAg.Olfactory_epithelium mm9 Unclassified Others Olfactory epithelium ...SRX112960 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Unc.Oth.10.AllAg.Olfactory_epithelium.bed ...

  12. Localization and Expression of Zonula Occludins-1 in the Rabbit Corneal Epithelium following Exposure to Benzalkonium Chloride

    Science.gov (United States)

    Zhang, Zhenhao; Chen, Lelei; Xie, Hui; Dong, Nuo; Chen, Yongxiong; Liu, Zuguo

    2012-01-01

    Preservatives are a major component of the ophthalmic preparations in multi-dose bottles. The purpose of this study was to investigate the acute effect of benzalkonium chloride (BAC), a common preservative used in ophthalmic preparations, on the localization and expression of zonula occludens (ZO)-1 in the rabbit corneal epithelium in vivo. BAC at 0.005%, 0.01%, or 0.02% was topically applied to one eye each of albino rabbits at 5 min intervals for a total of 3 times. The contralateral untreated eyes served as controls. The following clinical indications were evaluated: Schirmer test, tear break-up time (BUT), fluorescein and rose Bengal staining. The structure of central cornea was examined by in vivo confocal microscopy, and the corneal barrier function was evaluated by measurement of corneal transepithelial electrical resistance and permeability to carboxy fluorescein. Whole mount corneas were analyzed by using fluorescence confocal microscopy for the presence of ZO-1, 2, occludin, claudin-1, Ki67 and cell apoptosis in the epithelium. The expression of ZO-1 in the corneal epithelium was also examined by western blot and reverse transcription-polymerase chain reaction analyses. Exposure to BAC resulted in higher rose Bengal staining scores while no significant changes in BUT, Schirmer and corneal florescein scores. It also induced corneal epithelial cell damage, dispersion of ZO-1 and ZO-2 from their normal locus at the superficial layer and disruption of epithelial barrier function. However, the amounts of ZO-1 mRNA and protein in the corneal epithelium were not affected by BAC treatment. Exposure to BAC can quickly impair the corneal epithelium without tear deficiency. BAC disrupts the tight junctions of corneal epithelium between superficial cells in the rabbit corneal epithelium in vivo. PMID:22815857

  13. Localization and expression of zonula occludins-1 in the rabbit corneal epithelium following exposure to benzalkonium chloride.

    Directory of Open Access Journals (Sweden)

    Wensheng Chen

    Full Text Available Preservatives are a major component of the ophthalmic preparations in multi-dose bottles. The purpose of this study was to investigate the acute effect of benzalkonium chloride (BAC, a common preservative used in ophthalmic preparations, on the localization and expression of zonula occludens (ZO-1 in the rabbit corneal epithelium in vivo. BAC at 0.005%, 0.01%, or 0.02% was topically applied to one eye each of albino rabbits at 5 min intervals for a total of 3 times. The contralateral untreated eyes served as controls. The following clinical indications were evaluated: Schirmer test, tear break-up time (BUT, fluorescein and rose Bengal staining. The structure of central cornea was examined by in vivo confocal microscopy, and the corneal barrier function was evaluated by measurement of corneal transepithelial electrical resistance and permeability to carboxy fluorescein. Whole mount corneas were analyzed by using fluorescence confocal microscopy for the presence of ZO-1, 2, occludin, claudin-1, Ki67 and cell apoptosis in the epithelium. The expression of ZO-1 in the corneal epithelium was also examined by western blot and reverse transcription-polymerase chain reaction analyses. Exposure to BAC resulted in higher rose Bengal staining scores while no significant changes in BUT, Schirmer and corneal florescein scores. It also induced corneal epithelial cell damage, dispersion of ZO-1 and ZO-2 from their normal locus at the superficial layer and disruption of epithelial barrier function. However, the amounts of ZO-1 mRNA and protein in the corneal epithelium were not affected by BAC treatment. Exposure to BAC can quickly impair the corneal epithelium without tear deficiency. BAC disrupts the tight junctions of corneal epithelium between superficial cells in the rabbit corneal epithelium in vivo.

  14. Election Spin Resonance Studies of Free Radical Formation and Oxygen Consumption of Lens Epithelium During Ultraviolet Exposure

    Institute of Scientific and Technical Information of China (English)

    1993-01-01

    A long life election spin resonance (ESR) signal at g=2.0006 was observed in the normal lens epithelium and cortical fibers. During ultraviolet (UV) exposure, a new ESR signal at g = 2.0060 was found in the lens epithelium. But this specific signal was not detected in the lens cortical fibers. This suggested that lens epithelial cells were more susceptible to the free radical formation which was induced by UV light. By means of ESR spin probe oxymetry, the oxygen uptake of lens epithelial cells was meas...

  15. Left Circumflex Coronary Artery Fistula Connected to the Right Bronchial Artery Associated with Bronchiectasis: Multidetector CT and Coronary Angiography Findings

    Energy Technology Data Exchange (ETDEWEB)

    Nam, Kyung Jin; Choo, Ki Seok [Dept. of Radiology, Medical Research Institute, Pusan National University Yangsan Hospital, Pusan National University School of Medicine, Yangsan (Korea, Republic of)

    2013-04-15

    Coronary to bronchial artery fistula is a rare vascular anomaly secondary to enlargement of pre-existing vascular anastomosis between the coronary and bronchial arteries. This occurs when there is a constant disturbance of the pressure equilibrium involving either coronary or broncho-pulmonary disorder. Localized bronchiectasis is the most common related condition in patients with a coronary to bronchial artery fistula. Herein, we report on a case of a large left circumflex coronary artery to right bronchial artery fistula associated with bronchiectasis.

  16. EOTAXIN AND EOTAXIN-2 EXPRESSION IN HUMAN BRONCHIAL EPITHELIAL CELL

    Institute of Scientific and Technical Information of China (English)

    TANG Wei; DENG Wei-wu; Albert CHAN; Stanley CHIK; Adrain WU

    2005-01-01

    Objective To study the role of eotaxin and eotaxin-2 expression by Th2 cytokine and analyze their relationship in normal human bronchial epithelial cell line-BEAS-2B cell. Methods Levels of eotaxin mRNA and protein expression in the bronchial epithelial cell line BEAS-2B cell were determined with RT-PCR and ELISA. We also used RT-PCR to evaluate eotaxin-2 expression under the regulation of Th2 cytokine IL-4 and IL-13 as well as proinflammatory agent-TNFα. Results Eotaxin mRNA expression was the highest at the time point of 12h under the stimulation of TNF-α. While Th2 cytokine IL-4 and IL-13 had the amplification effect on the expression. Eotaxin protein was also elevated with the combination stimulation of proinflammatory agent TNF-α and IL-4 in dose and time dependent manner(P<0.01). These results were also seen when the cells were stimulated by TNF-α and IL-13. Eotaxin-2 mRNA expression was the highest at the time point of 8h. The expression evaluated by semi-quantitative RT-PCR also elevated under the co-stimulation of TNF-α and IL-4 or TNF-α and IL-13 and it should significantly correlate with Eotaxin(P<0.05). Conclusion This study demonstrated that Th2 cytokine like IL-4 and IL-13 enhances eotaxin and eotaxin-2 expression when co-stimulated with proinflammatory agent TNF-α. These results showed that Th2 cytokines existence is the strong evidence for bronchial epithelial cells taking part in the allergic inflammation especially in eosinophils recruitment.

  17. Eosinophils in the bronchial mucosa in relation to methacholine dose-response curves in atopic asthma

    NARCIS (Netherlands)

    G.M. Moller (Trude); S.E. Overbeek (Shelley); C.G. van Helden-Meeuwsen; H.C. Hoogsteden (Henk); J.M. Bogaard (Jan)

    1999-01-01

    textabstractAsthma is characterized by both local infiltration of eosinophils in the bronchial mucosa and bronchial hyperreactivity (BHR). A detailed characterization of BHR implies analysis of a histamine or methacholine dose-response curve yielding not only the dose a

  18. HMGA1 drives metabolic reprogramming of intestinal epithelium during hyperproliferation, polyposis, and colorectal carcinogenesis.

    Science.gov (United States)

    Williams, Michael D; Zhang, Xing; Belton, Amy S; Xian, Lingling; Huso, Tait; Park, Jeong-Jin; Siems, William F; Gang, David R; Resar, Linda M S; Reeves, Raymond; Hill, Herbert H

    2015-03-01

    Although significant progress has been made in the diagnosis and treatment of colorectal cancer (CRC), it remains a leading cause of cancer death worldwide. Early identification and removal of polyps that may progress to overt CRC is the cornerstone of CRC prevention. Expression of the High Mobility Group A1 (HMGA1) gene is significantly elevated in CRCs as compared with adjacent, nonmalignant tissues. We investigated metabolic aberrations induced by HMGA1 overexpression in small intestinal and colonic epithelium using traveling wave ion mobility mass spectrometry (TWIMMS) in a transgenic model in which murine Hmga1 was misexpressed in colonic epithelium. To determine if these Hmga1-induced metabolic alterations in mice were relevant to human colorectal carcinogenesis, we also investigated tumors from patients with CRC and matched, adjacent, nonmalignant tissues. Multivariate statistical methods and manual comparisons were used to identify metabolites specific to Hmga1 and CRC. Statistical modeling of data revealed distinct metabolic patterns in Hmga1 transgenics and human CRC samples as compared with the control tissues. We discovered that 13 metabolites were specific for Hmga1 in murine intestinal epithelium and also found in human CRC. Several of these metabolites function in fatty acid metabolism and membrane composition. Although further validation is needed, our results suggest that high levels of HMGA1 protein drive metabolic alterations that contribute to CRC pathogenesis through fatty acid synthesis. These metabolites could serve as potential biomarkers or therapeutic targets.

  19. Central bronchial carcinoid: Management of a case and anesthetic perspectives

    Science.gov (United States)

    Goswami, D; Kashyap, L; Batra, RK; Bhagat, C

    2016-01-01

    Obstructing lesions of the central airways present with a variety of symptoms and are often associated with pneumonia or asthma-like states. Anesthesia to these patients often presents challenges right from the preoperative stabilization of underlying lung condition, mask ventilation in the supine position to maintaining oxygenation and ventilation in the intraoperative and postoperative period. We present here a case of a young woman with a central bronchial tumor with significant airway obstruction with potential for major bleeding and subsequent anesthetic management without lung sacrificing measures and cardiopulmonary bypass assistance. PMID:26955320

  20. Central bronchial carcinoid: Management of a case and anesthetic perspectives

    Directory of Open Access Journals (Sweden)

    D Goswami

    2016-01-01

    Full Text Available Obstructing lesions of the central airways present with a variety of symptoms and are often associated with pneumonia or asthma-like states. Anesthesia to these patients often presents challenges right from the preoperative stabilization of underlying lung condition, mask ventilation in the supine position to maintaining oxygenation and ventilation in the intraoperative and postoperative period. We present here a case of a young woman with a central bronchial tumor with significant airway obstruction with potential for major bleeding and subsequent anesthetic management without lung sacrificing measures and cardiopulmonary bypass assistance.

  1. Bronchial atresia in a neonate with congenital cytomegalovirus infection

    Directory of Open Access Journals (Sweden)

    Abdullah A Yousef

    2013-01-01

    Full Text Available Bronchial atresia (BA is characterized by a mucus-filled bronchocele in a blind-ending segmental or lobar bronchus with hyperinflation of the obstructed segment of the lung. We describe a neonate who presented on his 9 th day of life with respiratory distress. Chest computed tomography showed a soft tissue density involving the right middle lobe (RML. RML lobectomy confirmed the diagnosis of BA. Cytomegalovirus was detected by polymerase chain reaction in blood, urine, and tracheal aspirates which may provide further insight into the pathogenesis of BA.

  2. Scale dependence of branching in arterial and bronchial trees

    CERN Document Server

    Restrepo, J G; Hunt, B R; Restrepo, Juan G.; Ott, Edward; Hunt, Brian R.

    2005-01-01

    Although models of branching in arterial and bronchial trees often predict a dependence of bifurcation parameters on the scale of the bifurcating vessels, direct verifications of this dependence with data are uncommon. We compare measurements of bifurcation parameters in airways and arterial trees of different mammals as a function of scale to general features predicted by theoretical models. We find that the size dependence is more complex than existing theories based solely on energy minimization explain, and suggest additional factors that may govern the branching at different scales.

  3. Topical retinoic acid changes the epidermal cell surface glycosylation pattern towards that of a mucosal epithelium

    DEFF Research Database (Denmark)

    Griffiths, C E; Dabelsteen, Erik; Voorhees, J J

    1996-01-01

    for carbohydrate synthesis, are influenced by retinoids. Thus, we investigated whether epidermal cell surface glycosylation is altered in skin treated with topical RA, and contrasted it with changes induced by topical SLS. Skin biopsies were obtained from seven normal volunteers who had been treated, on three......-treated epidermis was not significantly different from that observed after vehicle treatment. Thus, RA treatment converts normal stratified epithelium towards the phenotype of mucosal epithelium with a decrease in T antigen and a concomitant increase in Ley. These changes are not observed following treatment......Topical all-trans retinoic acid (RA) produces a number of epidermal changes which are indistinguishable from those observed following treatment with a local irritant, namely sodium lauryl sulphate (SLS). This observation has led to criticism that the efficacy of RA in disorders such as photoageing...

  4. A new, band-shaped and whorled microcystic dystrophy of the corneal epithelium.

    Science.gov (United States)

    Lisch, W; Steuhl, K P; Lisch, C; Weidle, E G; Emmig, C T; Cohen, K L; Perry, H D

    1992-07-15

    Five family members and three unrelated patients (four women, four men, 23 to 71 years old) had a dystrophy of the corneal epithelium. Direct slit-lamp examination showed bilateral or unilateral, gray, band-shaped, and feathery opacities that sometimes appeared in whorled patterns. Retroillumination showed intraepithelial, densely crowded, clear microcysts. Light and electron microscopy disclosed diffuse vacuolization of the cytoplasm of epithelial cells in the affected area. Visual acuity was so reduced in three patients that abrasion of the corneal epithelium was performed. The corneal abnormalities recurred within months, with the same reduction in visual acuity as before. The corneal opacities were progressive in two patients but diminished noticeably in another after he began using a hard contact lens. We found no other ophthalmic irregularities or associated systemic abnormalities and no indication of drug-induced keratopathy.

  5. Crosstalk between B lymphocytes, microbiota and the intestinal epithelium governs immunity versus metabolism in the gut

    Science.gov (United States)

    Shulzhenko, Natalia; Morgun, Andrey; Hsiao, William; Battle, Michele; Yao, Michael; Gavrilova, Oksana; Orandle, Marlene; Mayer, Lloyd; Macpherson, Andrew J; McCoy, Kathy D; Fraser-Liggett, Claire; Matzinger, Polly

    2014-01-01

    Using a systems biology approach, we discovered and dissected a three-way interaction between the immune system, the intestinal epithelium and the microbiota. We found that, in the absence of B cells, or of IgA, and in the presence of the microbiota, the intestinal epithelium launches its own protective mechanisms, upregulating interferon-inducible immune response pathways and simultaneously repressing Gata4-related metabolic functions. This shift in intestinal function leads to lipid malabsorption and decreased deposition of body fat. Network analysis revealed the presence of two interconnected epithelial-cell gene networks, one governing lipid metabolism and another regulating immunity, that were inversely expressed. Gene expression patterns in gut biopsies from individuals with common variable immunodeficiency or with HIV that also have intestinal malabsorption were very similar to those of the B cell–deficient mice, providing a possible explanation for a longstanding enigmatic association between immunodeficiency and defective lipid absorption in humans. PMID:22101768

  6. Regulation of the vitamin D receptor and cornifin beta expression in vaginal epithelium of the rats through vitamin D3

    Directory of Open Access Journals (Sweden)

    G Abban

    2009-08-01

    Full Text Available The aim of the present study was to determine the respective role of 1,25-dihydroxyvitamin D3 on vaginal epithelium and 1,25-dihydroxyvitamin D3 receptor expression in ovariectomized rats and vitamin D3 treated rats. Bilateral ovariectomies were performed in 20 mature, non-pregnant Wistar female rats. All the animals were divided into 2 groups consisting of 10 rats each. Group I served as control. In group II, animals were injected intramuscularly with vitamin D3 (50, 00 IU/kg. Two weeks after the injections, vaginas of animals in group I and group II were removed removed and processed for immunohistochemistry. Epithelial differentiation, 1,25-dihydroxyvitamin D3 receptor and cornifin b expression were investigated in vaginal epithelium of control group (ovariectomized and vitamin D3 treated rats. Vaginal epithelial cells from vitamin D3 treated animals changed into highly- stratified keratinizing layers. 1,25-dihydroxyvitamin D3 receptor and cornifin b as a marker of squamous differentiation were present in ovariectomized rats treated with 1,25- dihydroxyvitamin D3. In contrast, cornifin b and 1,25-dihydroxyvitamin D3 receptor were absent in all layers of vaginal epithelium in control group. We demonstrated for the first time that 1,25-dihydroxyvitamin D3 induced proliferation of vaginal epithelium consistent with the cornifin b expression and 1,25-dihydroxyvitamin D3 up-regulated 1,25-dihydroxyvitamin D3 receptor expression in vaginal epithelium.

  7. Combined laser phototherapy and growth factor treatment of bronchial obstruction after lung transplantation.

    Science.gov (United States)

    Hertz, M I; Harmon, K R; Knighton, D R; Cahill, B C; Duvall, A J; Shumway, S J; Bolman, R M

    1991-12-01

    Lung transplantation has resulted in dramatic functional improvement in patients with end-stage pulmonary diseases. Among the complications of lung transplantation are dehiscence and stenosis at the site of the bronchial or tracheal anastomosis. In this case report, we describe a single lung transplant recipient in whom partial bronchial dehiscence, followed by exuberant growth of granulation tissue, resulted in obstruction of the bronchial lumen. After mechanical dilation failed to produce lasting relief of bronchial obstruction, a novel approach to this problem was successfully employed: YAG laser phototherapy was used to remove obstructing granulation tissue, followed by application of a preparation derived from autologous blood platelets to promote epithelialization of the bronchial anastomosis. The bronchus remains patent and fully epithelialized six months after therapy.

  8. Remission of bronchial asthma after viral clearance in chronic hepatitis C

    Institute of Scientific and Technical Information of China (English)

    Norihiko Yamamoto; Kazumoto Murata; Takeshi Nakano

    2005-01-01

    A 53-year-old man with a history of blood transfusion at the age of 20 was admitted to our hospital because of liver dysfunction. He had bronchial asthma when he was 18 years old, which naturally resolved within 2 years. However, his bronchial asthma recurred at the age of 45 and was treated with oral theophylline. He was diagnosed as having chronic hepatitis C based on the histological and clinical findings, and then interferon (IFN) therapy was administered. The frequency of bronchial asthma attack was gradually decreasing after IFN therapy with marked improvement of hypereosinophilia. He achieved sustained viral response (SVR) and his bronchial asthma did not worsen even after the cessation of IFN. Hepatitis C virus (HCV) infection and IFN therapy were considered in the remission of asthma in this case. HCV infection could be the cause of bronchial asthma, especially in patients with late appearance of asthma.

  9. Expression level of TGF-β1, U-Ⅱ in patients with bronchial asthma

    Institute of Scientific and Technical Information of China (English)

    Shang-Sun Cai; Guo-Ping Wu; Yuan-Zheng Yang; Ping Rao; Guang-Yu Wang; Qiong-Lian Huang

    2015-01-01

    Objective: To investigate the expression level in the serum of patients with bronchial asthma in TGF-β1, U-Ⅱ and their correlation. Methods: U-Ⅱ was measured by radioimmunoassay and TGF-β1 was measured by double antibody sandwich ELISA method in 45 patients with acute bronchial asthma, 43 cases of bronchial asthma in remission period and 41 healthy subjects. The correlation between TGF-β1 and U-Ⅱ was also analyzed. Results: There were significant differences in TGF-β1 and U-Ⅱ between healthy subjects and bronchial asthma patients (P<0.01), and the differences between patients at acute stage and remission stage was also significant (P<0.01). TGF-β1 was positively correlated with U-Ⅱ (P<0.05). Conclusions:TGF-β1 and U-Ⅱ are important indicators for treatment of bronchial asthma.

  10. [Some modern views of the role of the eosinophils in allergic reactions and bronchial asthma and a new method of detecting eosinophils in the bronchial secretion].

    Science.gov (United States)

    Denchev, K; Lipcheva, N; Kis'ova, K

    1976-01-01

    A review of certain contemporary opinions of eosinophil function in allergic reactions and bronchial asthma is presented in this report. Phagocytosis and processing of the complexes antigenantibody, histamine inhibition and a histamine elimination elimination by a specific inhibitor, isolated from eosinophilis (EDI), stimulation of prostaglandines E release, which also inhibit histamine and have a bronchial dilataion effect. The new method is recommended for eosinophil detection in sputa based on the fluorescent principle as faster and more efficient.

  11. Stroma-epithelium crosstalk in prostate cancer

    Institute of Scientific and Technical Information of China (English)

    Yi-Nong Niu; Shu-Jie Xia

    2009-01-01

    The critical role played by stroma-epithelium crosstalk in carcinogenesis and progression of prostate cancer has been increasingly recognized.These interactions are mediated by a variety of paracrine factors secreted by cancer cells and/or stromal cells.In human prostate cancer,reactive stroma is characterized by an increase in myofibroblasts and a corresponding amplification of extracellular matrix production and angiogenesis.Permanent genetic mutations have been reported in stromal cells as well as in turnout cells.Transforming growth factor-β,vascular endothelial growth factor,platelet-derived growth factor and fibroblast growth factor signalling pathways are involved in the process of angiogenesis,whereas hepatocyte growth factor,insulin-like growth factor-1,epidermal growth factor,CXC12 and Interleukin-6 play active roles in the progression,androgen-independent conversion and distal metastasis of prostate cancer.Some soluble factors have reciprocal interactions with androgens and the androgen receptor (AR),and can even activate AR in the absence of the androgen ligand.In this article,we review the complex interactions between cancer cells and the surrounding microenvironment,and discuss the potential therapeutic targets in the stromal compartment of prostate cancer.

  12. Oral epithelium in diabetics: A cytomorphometric correlation

    Directory of Open Access Journals (Sweden)

    K P Nandita

    2014-01-01

    Full Text Available Objectives: The study aims to establish an etiological association between diabetes and precancerous lesions of the oral cavity by cytomorphometric analysis of the oral epithelium. Study Design: Smears were obtained from three distinct oral sites - buccal mucosa, dorsum of the tongue and the floor of the mouth in ten controls and ten patients previously diagnosed with type II diabetes. The oral smears were stained with Papanicolaou SA-36 solution. An eye - piece graticule was used to obtain the cytoplasm and nuclear dimension; where larger dimension was denoted as "D" and the smaller dimension was denoted as "d". The nuclear area (NA, nuclear diameter (ND, cytoplasmic area (CA and the cytoplasmic / nuclear ratio (C/N were evaluated from 50 cells predominant in each oral site. Statistical Analysis: The cytomorphometric data obtained was compared between the group of diabetic patients and the control groups using the student′s t- test (SPSS version 11.0. Results: Results showed that the nuclear area and the nuclear diameter of oral epithelial cells were increased in diabetic patients, as compared to non- diabetics, while the non- diabetic patients demonstrated an increase in nuclear ratio. Conclusions: The results from this study suggest that diabetes mellitus can cause alterations in oral epithelial cells that are detectable with exfoliative cytology.

  13. Human vomeronasal epithelium development: An immunohistochemical overview.

    Science.gov (United States)

    Dénes, Lóránd; Pap, Zsuzsanna; Szántó, Annamária; Gergely, István; Pop, Tudor Sorin

    2015-06-01

    The vomeronasal organ (VNO) is the receptor structure of the vomeronasal system (VNS) in vertebrates. It is found bilaterally in the submucosa of the inferior part of the nasal septum. There are ongoing controversies regarding the functionality of this organ in humans. In this study we propose the immunohistochemical evaluation of changes in components of the human vomeronasal epithelium during foetal development. We used 45 foetuses of different age, which were included in three age groups. After VNO identification immunohistochemical reactions were performed using primary antibodies against the following: neuron specific enolase, calretinin, neurofilament, chromogranin, synaptophysin, cytokeratin 7, pan-cytokeratin and S100 protein. Digital slides were obtained and following colorimetric segmentation, surface area measurements were performed. The VNO was found in less than half of the studied specimens (42.2%). Neuron specific enolase and calretinin immunoexpression showed a decreasing trend with foetal age, while the other neural/neuroendocrine markers were negative in all specimens. Cytokeratin 7 expression increased with age, while Pan-Ctk had no significant variations. S100 protein immunoexpression also decreased around the VNO. The results of the present work uphold the theory of regression of the neuroepithelium that is present during initial stages of foetal development.

  14. Glucose metabolism in rat retinal pigment epithelium.

    Science.gov (United States)

    Coffe, Víctor; Carbajal, Raymundo C; Salceda, Rocío

    2006-01-01

    The retinal pigment epithelium (RPE) is the major transport pathway for exchange of metabolites and ions between choroidal blood supply and the neural retina. To gain insight into the mechanisms controlling glucose metabolism in RPE and its possible relationship to retinopathy, we studied the influence of different glucose concentrations on glycogen and lactate levels and CO(2) production in RPE from normal and streptozotocin-treated diabetic rats. Incubation of normal RPE in the absence of glucose caused a decrease in lactate production and glycogen content. In normal RPE, increasing glucose concentrations from 5.6 mM to 30 mM caused a four-fold increase in glucose accumulation and CO(2) yield, as well as reduction in lactate and glycogen production. In RPE from diabetic rats glucose accumulation did not increase in the presence of high glucose substrate, but it showed a four- and a seven-fold increase in CO(2) production through the mitochondrial and pentose phosphate pathways, respectively. We found high glycogen levels in RPE which can be used as an energy reserve for RPE itself and/or neural retina. Findings further show that the RPE possesses a high oxidative capacity. The large increase in glucose shunting to the pentose phosphate pathway in diabetic retina exposed to high glucose suggests a need for reducing capacity, consistent with increased oxidative stress.

  15. Building and maintaining the epithelium of the lung.

    Science.gov (United States)

    Rackley, Craig R; Stripp, Barry R

    2012-08-01

    Airspaces of the lung are lined by an epithelium whose cellular composition changes along the proximal-to-distal axis to meet local functional needs for mucociliary clearance, hydration, host defense, and gas exchange. Advances in cell isolation, in vitro culture techniques, and genetic manipulation of animal models have increased our understanding of the development and maintenance of the pulmonary epithelium. This review discusses basic cellular mechanisms that regulate establishment of the conducting airway and gas exchange systems as well as the functional maintenance of the epithelium during postnatal life.

  16. p38丝裂原活化蛋白激酶对耐火陶瓷纤维诱导人支气管上皮细胞凋亡的作用%Effects of p38 mitogen-activated protein kinases on the apoptosis of human bronchial epithelial cells induced by refractory ceramic fibers in vitro

    Institute of Scientific and Technical Information of China (English)

    张敏; 朱丽瑾; 肖芸; 张幸

    2013-01-01

    Objective To investigate the role of p38 mitogen-activated protein kinases (MAPKs) in the apoptosis of human bronchial epithelial cells (BEAS-2B) induced by refractory ceramic fibers (RCFs).Methods BEAS-2B cells were exposed to 10,20,40,80,and 160 μg/cm2 RCF1,RCF2,and RCF3 for 24 h,and the cell viability was measured by CCK-8 assay.BEAS-2B cells were exposed to 20,40,and 100 μg/cm2 RCF1,RCF2,and RCF3 for 24 h,and the cell apoptosis rate was measured by flow cytometry.BEAS-2B cells were exposed to 40 μg/cm2 RCF1,RCF2,and RCF3,and the expression levels of phospho-p38 MAPK and caspase-3 were measured by Western blot.In each of the above treatments,the BEAS-2B cells were divided into positive control,p38 inhibitor SB203580 intervention,and normal groups.Results As the concentration of RCFs rose,the RCF exposure groups showed decreased cell viability and increased cell apoptosis rate.After SB203580 intervention,the intervention groups (all concentrations of asbestos + SB,20,40,80,and 160 μg/cm2 RCF1+SB,and 40,80,and 160 μg/cm2 RCF2 and RCF3+SB) had significantly increased cell viabilities (P<0.05),and the intervention groups (asbestos + SB and 20,40,and 100 μg/cm2 RCF1,RCF2,and RCF3 + SB) had significantly decreased cell apoptosis rates (P<0.05).Compared with the normal group,the RCF (40 μg/cm2)exposure and positive control groups had significantly increased expression of phospho-p38 MAPK (P<0.05),and the RCF (40 μg/cm2) exposure group had significantly increased expression of caspase-3 (P<0.05).The intervention groups (asbestos + SB and 40 μg/cm2 RCF1,RCF2,and RCF3 + SB) had significantly decreased expression of caspase-3 after SB203580 intervention.Conclusion p38 MAPKs play an important role in RCFinduced apoptosis of BEAS-2B cells.%目的 p38丝裂原活化蛋白激酶(p38MAPK)在RCFs诱导BEAS-2B凋亡中的作用.方法 10、20、40、80、160 μg/cm2 RCF1、RCF2和RCF3诱导BEAS-2B细胞24 h,用CCK-8法检测细胞存活率;20、40、100 μg/cm2

  17. 过氧化氢诱导支气管上皮细胞高迁移率族蛋白1主动释放%Hydrogen peroxide induces high mobility group box 1 release in human bronchial epithelial cells

    Institute of Scientific and Technical Information of China (English)

    侯长春; 赵海金; 李文军; 蔡绍曦

    2012-01-01

    Objective To investigate the effect of hydrogen dioxide (H2O2) on the release and translocation of high mobility group box 1 release (HMGB1) from normal human bronchiolar epithelial cells (HBE). Methods MTT assay was used to assess the viability of HBE135-E6E7 cells exposed to different concentrations of H2O2. The expression and location of HMGB1 in the cytoplasm, nuclei and culture medium of the exposed cells were determined using Western blotting and immunofluorescence assay. Results Exposure to 125 μmmol/L H2O2 did not obviously affect the cell viability. At the concentration of 250 μmmol/L, H2O2 significantly decreased the cell viability (P<0.05), but significant cell death occurred only after exposure to 400 μmmol/L HA (P=0.000). Compared with the control cells, the cells exposed to 12.5, 125 and 250 μmmol/L H2O2 for 24 h showed significantly increased levels of HMGB1 in the culture medium (P<0.05), and exposure to 125 μmmol/L H2O2 for 12 and 24 h also caused significantly increased HMGB1 level (P<0,05). Exposure to 125 μmmol/L H2O2 for 24 h significantly increased HMGB1 expression in the cytoplasm but decreased its expression in the nucleus. HMGB1 translocation from the nuclei to the cytoplasm and to the plasmalemma occurred after 125 μmmol/L H2O2 exposure for 12 h and 24 h, respectively. Conclusion Haft can induce HMGB1 translocation and release in human bronchial epithelial cells, suggesting the involvement of HMGB1 in airway oxidative stress in chronic inflammatory diseases such as asthma and COPD.%目的 研究过氧化氢(H2O2)对正常人支气管上皮细胞(HBE)HMGB1表达、移位和释放的影响.方法 四唑盐(MTT)法检测不同浓度H2O2对支气管上皮细胞活力的影响;蛋白免疫印迹方法分别检测H2O2刺激HBE胞核,胞浆以及细胞培养上清中HMGB1浓度.免疫荧光观察HBE的HMGB1的定位和H2O2刺激后对HBE HMGB1的移位的影响.结果 125 μmmol/L刺激对HBE活力无影响,而250 μmmol/L会导致细

  18. Karyotyping of Chromosomes in Human Bronchial Epithelial Cells Transformed by High Energy Fe Ions

    Science.gov (United States)

    Yeshitla, Samrawit; Zhang, Ye; Park, Seongmi; Story, Michael D.; Wilson, Bobby; Wu, Honglu

    2015-01-01

    Lung cancer induced from exposures to space radiation is one of the most significant health risks for long-term space travels. Evidences show that low- and high- Linear energy transfer (LET)-induced transformation of normal human bronchial epithelial cells (HBEC) that are immortalized through the expression of Cdk4 and hTERT. The cells were exposed to gamma rays and high-energy Fe ions for the selection of transformed clones. Transformed HBEC are identified and analyzed chromosome aberrations (i.e. genomic instability) using the multi-color fluorescent in situ hybridization (mFISH), as well as the multi-banding in situ hybridization (mBAND) techniques. Our results show chromosomal translocations between different chromosomes and several of the breaks occurred in the q-arm of chromosome 3. We also identified copy number variations between the transformed and the parental HBEC regardless of the exposure conditions. We observed chromosomal aberrations in the lowand high-LET radiation-induced transformed clones and they are imperfectly different from clones obtain in spontaneous soft agar growth.

  19. Biological effects of atmospheric particles on human bronchial epithelial cells. Comparison with diesel exhaust particles.

    Science.gov (United States)

    Baulig, Augustin; Sourdeval, Matthieu; Meyer, Martine; Marano, Francelyne; Baeza-Squiban, Armelle

    2003-01-01

    Epidemiological studies have associated the increase of respiratory disorders with high levels of ambient particulate matter (PM) levels although the underlying biological mechanisms are unclear. PM are a complex mixture of particles with different origins but in urban areas, they mainly contain soots from transport like Diesel exhaust particles (DEP). In order to determine whether PM biological effects can be explained by the presence of DEP, the effects of urban PM, DEP and carbon black particles (CB) were compared on a human bronchial epithelial cell line (16-HBE14o-). Two types of PM were used : reference material (RPM) and PM with an aerodynamic diameter particles. However, DEP and to a lower extent PM inhibited cell proliferation, induced the release of a pro-inflammatory cytokine, GM-CSF, and generated a pro-oxidant state as shown by the increased intracellular peroxides production. By contrast, CB never induced such effects. Nevertheless CB are more endocytosed than DEP whereas PM are the less endocytosed particles. In conclusion, PM induced to a lower extent the same biological effects than DEP in 16-HBE cells suggesting that particle characteristics should be thoroughly considered in order to clearly correlate adverse effects of PM to their composition and to clarify the role of DEP in PM effects.

  20. Regulation of Tight Junctions in Upper Airway Epithelium

    Directory of Open Access Journals (Sweden)

    Takashi Kojima

    2013-01-01

    Full Text Available The mucosal barrier of the upper respiratory tract including the nasal cavity, which is the first site of exposure to inhaled antigens, plays an important role in host defense in terms of innate immunity and is regulated in large part by tight junctions of epithelial cells. Tight junction molecules are expressed in both M cells and dendritic cells as well as epithelial cells of upper airway. Various antigens are sampled, transported, and released to lymphocytes through the cells in nasal mucosa while they maintain the integrity of the barrier. Expression of tight junction molecules and the barrier function in normal human nasal epithelial cells (HNECs are affected by various stimuli including growth factor, TLR ligand, and cytokine. In addition, epithelial-derived thymic stromal lymphopoietin (TSLP, which is a master switch for allergic inflammatory diseases including allergic rhinitis, enhances the barrier function together with an increase of tight junction molecules in HNECs. Furthermore, respiratory syncytial virus infection in HNECs in vitro induces expression of tight junction molecules and the barrier function together with proinflammatory cytokine release. This paper summarizes the recent progress in our understanding of the regulation of tight junctions in the upper airway epithelium under normal, allergic, and RSV-infected conditions.

  1. Chronic alcohol ingestion changes the landscape of the alveolar epithelium.

    Science.gov (United States)

    Downs, Charles A; Trac, David; Brewer, Elizabeth M; Brown, Lou Ann; Helms, My N

    2013-01-01

    Similar to effects of alcohol on the heart, liver, and brain, the effects of ethanol (EtOH) on lung injury are preventable. Unlike other vital organ systems, however, the lethal effects of alcohol on the lung are underappreciated, perhaps because there are no signs of overt pulmonary disorder until a secondary insult, such as a bacterial infection or injury, occurs in the lung. This paper provides overview of the complex changes in the alveolar environment known to occur following both chronic and acute alcohol exposures. Contemporary animal and cell culture models for alcohol-induced lung dysfunction are discussed, with emphasis on the effect of alcohol on transepithelial transport processes, namely, epithelial sodium channel activity (ENaC). The cascading effect of tissue and phagocytic Nadph oxidase (Nox) may be triggered by ethanol exposure, and as such, alcohol ingestion and exposure lead to a prooxidative environment; thus impacting alveolar macrophage (AM) function and oxidative stress. A better understanding of how alcohol changes the landscape of the alveolar epithelium can lead to improvements in treating acute respiratory distress syndrome (ARDS) for which hospitalized alcoholics are at an increased risk.

  2. Preoperative Assessment of Different Treatment Modalities in Bronchial Asthma Patients

    Directory of Open Access Journals (Sweden)

    Kawther A. Azzam M.D. and **Sahar S. Khattab MD

    2003-06-01

    Full Text Available This study was performed to assess the effectiveness of acupuncture and medical therapies of bronchial asthma preoperatively. Sixty patients suffered from mild to moderate bronchial asthma and coming for elective operations were chozen from the outpatient clinic of Al-Zahraa University Hospital. Patients were randomly divided into three equal groups (n=20 each. Group I patients (drug group received oral theophylline and Salbutamol (ventolin inhaler according to the needs. Group II patients (drug +ear acupuncture group received same medical treatment as in group I and added ear acupuncture. Group III patients (drug + ear and body acupuncture group received same medical treatment as in group I and II and added ear and body acupuncture. Ventilatory function tests through spirometer and interleukin-13 estimation were performed before treatment and after two weeks of treatment. Improvement of subjective and objective parameters had occurred with significant decrease in the mean serum level of interleukin-13 and decrease in the mean number of using b-agonist puffs after two weeks of treatment in the three groups, with the best results being in group III than in group II and then in group I. Conclusion: Interleukin-13 estimation togheter with ventilatory function tests is a useful parameter for pre-operative assessment and evaluation of asthmatic patients. Also medication was significantly reduced when combined with acupuncture.

  3. Sputum as a source of adipokines in bronchial asthma

    Directory of Open Access Journals (Sweden)

    V. N. Mineev

    2014-01-01

    Full Text Available Forty-four patients with allergic (ABA and non-allergic (NABA variants of bronchial asthma (BA were examined to evaluate levels of key adipokines (leptin, resistin, adiponectin in sputum in different variants of BA. Adipokines in sputum and blood plasma were measured by Enzyme-Linked Immunosorbent Assay (ELISA. The indices that reflect the percentage of adipokines in sputum regarding adipokines in plasma of the same patients were worked out to evaluate the ratio of levels of corresponding adipokines in plasma and sputum in patients with BA. Two regularities are clearly seen in the study: the first - levels of proinflammatory adipokines (leptin, resistin in sputum in ABA correlate directly with indicators of respiratory function but levels of anti-inflammatory adipokines (adiponectin in sputum correlate inversely with indicators of respiratory function; the second -correlation of levels of the studied adipokines with indicators of respiratory function are almost not revealed in NABA. The first regularity reflects the important fact that the content of adipokines in bronchial secretion is to a certain extent one of regulating local mechanisms in target organ controlled system levels of corresponding adipokines in exacerbation of BA.

  4. Gastro-bronchial fistula after laparoscopic nissen fundoplication.

    Science.gov (United States)

    Faraj, Walid; Khalifeh, Mohamad; Soweid, Asaad; Habli, Nader; Selmo, Francesca; Priest, Oliver; Jamali, Faek R

    2007-10-01

    Gastro-bronchial fistula (GBF) is an unusual complication of Nissen fundoplication, particularly when performed via a transabdominal approach. The mechanism of such fistula is thought to be related to a previously untreated ulcer in the mucosa of the wall of the gastric wrap or to a subclinical injury to the gastric wall during the process of division of the short gastric vessels and gastric mobilization. This process is greatly aided by herniation of the wrap into the chest in the postoperative period, placing the stomach in intimate contact with the bronchial tree. The diagnosis of GBF is often difficult to establish and requires a high index of suspicion. Most investigative studies tend to be unrevealing. Historically, an upper gastrointestinal series was the recommended study of choice in the literature. Newer reports, however, highlight the value and importance of upper endoscopy as a diagnostic tool in this condition. The majority of GBF were reported in the era of transthoracic Nissen fundoplication. The incidence of this complication seems to have markedly decreased after the widespread adoption of the transabdominal approach to the treatment of GERD. We are reporting the second case in the literature of a GBF developing after a laparoscopic Nissen fundoplication in a 28-year-old male patient. This case report should serve to increase awareness of this uncommon complication that should be considered in the differential diagnosis of patients with recurrent pneumonia or refractory hemoptysis after major upper gastrointestinal surgical procedures.

  5. Radiologic management of haemoptysis. Diagnostic and interventional bronchial arterial embolisation

    Energy Technology Data Exchange (ETDEWEB)

    Ittrich, H.; Adam, G. [Univ. Medical Center Hamburg, Hamburg (Germany). Diagnostic and Interventional Radiology Dept. and Clinic; Klose, H. [Univ. Medical Center Hamburg, Hamburg (Germany). Section Pneumology

    2015-04-15

    Hemoptysis can be a life-threatening pulmonary emergency with high mortality, is symptomatic of an underlying severe pulmonary disease and requires immediate diagnosis and treatment. Diagnostically, bronchoscopy, conventional chest x-ray and contrast-enhanced multislice computed tomography (MSCT) with CT angiography (CTA) provide information regarding the underlying pulmonary disease, bleeding site, the vascular anatomy of the bronchial arteries (BA) and extrabronchial branches, as well a basis for planning of endovascular intervention. Therapeutically, bronchial artery embolization (BAE) is a safe and effective technique in the hands of an experienced interventionist with profound knowledge of the BA anatomy and possible pitfalls as well as experience with first-line therapy of recurrent and massive hemoptysis or as an intervention prior to elective surgery. Recurrent episodes of hemoptysis are not uncommon and require a prompt repeat BAE after exclusion of extrabronchial systemic and pulmonary artery bleeding sources. This review article should give an overview of the history, anatomical and pathophysiological basics and the clinical context of hemoptysis and diagnosis, as well as a survey of management, treatment and results of BAE.

  6. Ultrastructural study of grafted autologous cultured human epithelium.

    Science.gov (United States)

    Aihara, M

    1989-01-01

    An electron microscopical study of grafted autologous cultured human epithelium is presented. Biopsy samples were collected from four patients with full thickness burns at 9 days, 6 weeks and 5-21 months after grafting of the cultured epithelium. By the sixth week after transplantation, grafted cultured epithelial sheets had developed to consist of 10 to 20 layers of cells and the epithelium showed distinct basal, spinous, granular and horny layers, and a patchy basement membrane had formed. Langerhans cells and melanocytes were identifiable. From 5 months onwards flat basal cells became oval, and oval keratohyalin granules in the keratinocytes also assumed a normal irregular shape. Membrane-coating granules in the keratinocytes increased in number. The fine structures of desmosomes also showed a normal mature appearance. Furthermore, complete extension of the basement membrane could be observed. The maturation of cultured human epithelium is complete by 5 months after grafting.

  7. Identified Circadian Rhythm Genes of Ciliary Epithelium with Differential Display

    Institute of Scientific and Technical Information of China (English)

    Yanxia Li; Dongcheng Lu; Jian Ge; Yanna Li; Yehong Zhuo; Sears ML

    2001-01-01

    Purpose:To identify differential genes expressed in the rabbit ciliary epithelium duringthe circadian cycle of aqueous flow.Methods: Total RNA from ciliary epithelium of rabbits at 8AM (light on 1 hour) and8PM(light off 1 hour) were compared by differential display reverse transcription-polymerase chain reaetion(DD RT-PCR), using 6 % denaturing polyacrylamide electro-phoresis, choose differential display bands, cut and reamplify with the same primer, cloneand sequence. Search the database of Genbank, prolong them with 5' RACE and 3'RACE technique then clone, sequence and search database of Genbank.Results: 93 Significant differences gene expression were detected between light on andlight off in the rabbit ciliary epithelium.Conclusion: Differential display is a powerful tool to screen differentially expressedgenes in circadian rhythm of ciliary epithelium.

  8. Buccal Epithelium in treating Ocular Surface Disorders

    Directory of Open Access Journals (Sweden)

    Srinivas KR

    2008-11-01

    Full Text Available Background - Ocular surface disorders due to limbal stem cell deficiency are an important cause of ocular morbidity and visual loss. Although autologous limbal stem cell transplants have helped in the management of unilateral disease, allografts in those with bilateral disease often fail due to immunological reasons. The use of autologous buccal epithelium cultivated on amniotic membrane has been described as a useful approach in the management of this condition. It is the purpose of this study to explore the feasibility of using a novel thermo-gelatin polymer (TGP as a substrate to culture these cells, and to characterize them using RNA extraction and RT-PCR. Methods - Oral cheek mucosal biopsies were obtained from 5 adult patients undergoing Modified Osteo-Odonto Keratoprosthesis surgery. The specimens were transported to the laboratory in transport medium. The cells were released using enzymatic digestion and seeded in both convention culture medium and TGP. The resulting cellular growth was characterized using RNA extraction and RT-PCR. Results - Cells could be cultured from 4 of the 5 specimens. In one specimen, contamination occurred and this was discarded. In the other specimens, the cheek epithelial cells could be cultured in both the conventional culture medium and TGP, with equal ease. RT-PCR revealed the presence of K3, a marker for epithelial cells, and GAPDH indicating the presence of some adipose tissue as well. Conclusions - It is possible to culture autologous cheek mucosal epithelial cells using TGP, a synthetic scaffold, without the need for other biological substrates. Since the specimens are obtained from the oral cavity, stringent asepsis is required. Further studies are required for histopathological characterization of the cultured cells and to create a model for delivery onto the ocular surface of eyes with bilateral surface disease due to limbal stem cell deficiency.

  9. Detachments of the retinal pigment epithelium at the posterior pole.

    Science.gov (United States)

    Noble, K G; Levitzky, M J; Carr, R E

    1976-08-01

    Multiple vitelliform cysts of the retina, a disorder of unknown cause in which there are multiple detachments of the retinal pigment epithelium at the posterior pole, occurred in five patients. In four patients all lesions were located outside the parafoveal area while one patient showed bilateral foveal elevations associated with more eccentric detachments. Several patients showed slow resolution of some of the detachments with mild disturbances of the pigment epithelium.

  10. Reconstructing lineage hierarchies of the distal lung epithelium using single-cell RNA-seq.

    Science.gov (United States)

    Treutlein, Barbara; Brownfield, Doug G; Wu, Angela R; Neff, Norma F; Mantalas, Gary L; Espinoza, F Hernan; Desai, Tushar J; Krasnow, Mark A; Quake, Stephen R

    2014-05-15

    The mammalian lung is a highly branched network in which the distal regions of the bronchial tree transform during development into a densely packed honeycomb of alveolar air sacs that mediate gas exchange. Although this transformation has been studied by marker expression analysis and fate-mapping, the mechanisms that control the progression of lung progenitors along distinct lineages into mature alveolar cell types are still incompletely known, in part because of the limited number of lineage markers and the effects of ensemble averaging in conventional transcriptome analysis experiments on cell populations. Here we show that single-cell transcriptome analysis circumvents these problems and enables direct measurement of the various cell types and hierarchies in the developing lung. We used microfluidic single-cell RNA sequencing (RNA-seq) on 198 individual cells at four different stages encompassing alveolar differentiation to measure the transcriptional states which define the developmental and cellular hierarchy of the distal mouse lung epithelium. We empirically classified cells into distinct groups by using an unbiased genome-wide approach that did not require a priori knowledge of the underlying cell types or the previous purification of cell populations. The results confirmed the basic outlines of the classical model of epithelial cell-type diversity in the distal lung and led to the discovery of many previously unknown cell-type markers, including transcriptional regulators that discriminate between the different populations. We reconstructed the molecular steps during maturation of bipotential progenitors along both alveolar lineages and elucidated the full life cycle of the alveolar type 2 cell lineage. This single-cell genomics approach is applicable to any developing or mature tissue to robustly delineate molecularly distinct cell types, define progenitors and lineage hierarchies, and identify lineage-specific regulatory factors.

  11. HISTOGENESIS AND MORPHOGENESIS OF HUMAN LARYNGEAL EPITHELIUM: A PRENATAL STUDY

    Directory of Open Access Journals (Sweden)

    Rachna

    2015-04-01

    Full Text Available The anatomy of epithelium of human foetal larynx has not been fully described . In the present study we observed the development of epithelium of human larynx , in 40 fetuses with gestational ages ranging from 75mm C . R . L . ( crown rump length to 220mm C . R . L . ( C rown rump length . Tissues were prepared for microtomy by paraffin wax embedding method . Step sections ( every fifth were fixed and stained by Hematoxylin and Eosin ( H&E and Masson’s Trichrome method . In the present study , the entire laryngeal cavity is lined uniformily by respiratory epithelium initially , i . e ., ciliated pseudostratified columnar type . Later on the epithelium over the true vocal cords and dorsal surface of the epiglottis changes into stratified squamous type . Besides , there is flattenin g of epithelium , over the true vocal cords as a result of desquamation . Larynx , though is a common organ to reptiles , amphibians and mamm a ls with function of breathing , sound production and preventing food particles going into the trachea but the advancement of human has make it a very important organ for physicians , paediatricians , otorhinolaryngologists etc . So the knowle d ge of anatomy of fetal airway and its development is important for the diagnosis and treatment of various diseases . Our aim wa s to study the type of epithelium during different stages of development of human fetal larynx

  12. Bronchial morphometry in smokers: comparison with healthy subjects by using 3D CT

    Energy Technology Data Exchange (ETDEWEB)

    Montaudon, Michel [Unite d' Imagerie Thoracique, CHU de Bordeaux, Pessac (France); Universite Bordeaux 2, Laboratoire de Physiologie Cellulaire Respiratoire, Bordeaux (France); INSERM, Bordeaux (France); Hopital Cardiologique, Unite d' Imagerie Thoracique, Pessac (France); Berger, Patrick; Marthan, Roger [Universite Bordeaux 2, Laboratoire de Physiologie Cellulaire Respiratoire, Bordeaux (France); INSERM, Bordeaux (France); Service d' Exploration Fonctionnelle Respiratoire, CHU de Bordeaux, Pessac (France); Lederlin, Mathieu [Unite d' Imagerie Thoracique, CHU de Bordeaux, Pessac (France); Tunon-de-Lara, Jose Manuel [Universite Bordeaux 2, Laboratoire de Physiologie Cellulaire Respiratoire, Bordeaux (France); INSERM, Bordeaux (France); Service des Maladies Respiratoires, CHU de Bordeaux, Pessac (France); Laurent, Francois [Unite d' Imagerie Thoracique, CHU de Bordeaux, Pessac (France); Universite Bordeaux 2, Laboratoire de Physiologie Cellulaire Respiratoire, Bordeaux (France); INSERM, Bordeaux (France)

    2009-06-15

    The assessment of airway dimensions in patients with airway disease by using computed tomography (CT) has been limited by the obliquity of bronchi, the ability to identify the bronchial generation, and the limited number of bronchial measurements. The aims of the present study were (i) to analyze cross-sectional bronchial dimensions after automatic orthogonal reconstruction of all visible bronchi on CT images, and (ii) to compare bronchial morphometry between smokers and nonsmokers. CT and pulmonary function tests were performed in 18 males separated into two groups: 9 nonsmokers and 9 smokers. Bronchial wall area (WA) and lumen area (LA) were assessed using dedicated 3D software able to provide accurate cross-sectional measurements of all visible bronchi on CT. WA/LA and WA/(WA+LA) ratios were computed and all parameters were compared between both groups. Smokers demonstrated greater WA, smaller LA, and consequently greater LA/WA and LA/(WA+LA) ratios than nonsmokers. These differences occurred downward starting at the fourth bronchial generation. 3D quantitative CT method is able to demonstrate significant changes in bronchial morphometry related to tobacco consumption. (orig.)

  13. [Coexistence of bronchial asthma and diabetes mellitus type 2--retrospective analysis].

    Science.gov (United States)

    Glück, J; Rogala, B

    1999-01-01

    Bronchial asthma and diabetes mellitus type 2 are often found among adult patients. However, coincidence of these two diseases is very rare. The aim of the study was the retrospective analysis of all patients with bronchial asthma and diabetes mellitus type 2 hospitalised in Department and Clinic of Internal Diseases and Allergology in Zabrze, Silesian School of Medicine in Katowice in 1988-1997. Diabetes mellitus type 2 was diagnosed according to WHO criteria of 1985 and bronchial asthma was diagnosed with the use of American Thoracic Society criteria. Bronchial asthma and diabetes mellitus type 2 occurring together were found in 18 patients (0.3% of all hospitalized patients). In most patients the symptoms of bronchial asthma preceded the diagnosis of diabetes mellitus by a few years. All these cases were heterogeneous in terms of the duration of the diseases, clinical picture, and therapeutical approaches. In patients with bronchial asthma the existence of diabetes mellitus type 2 was not related to use of glikocorticosteroids. Patients in whom the coexistence of bronchial asthma and diabetes mellitus type 2 was found should be subjects of further studies to extend our knowledge of patomechanism of these diseases.

  14. [Response mechanisms of the airway smooth muscle tissue in experimental bronchial spasm].

    Science.gov (United States)

    Zashikhin, A L; Agafonov, Iu V; Barmina, A O

    2009-01-01

    This investigation was aimed at the complex evaluation of the reactivity mechanisms of bronchial smooth muscle tissue (SMT) in experimental bronchial spasm. Morphometric, cytospectrophotometric and electron microscopical analysis demonstrated the presence of three types of smooth muscle cells (SMC) within the bronchial SMT (small, medium, large), that differed in their linear and metabolic parameters. The findings of this study indicate that under the conditions of experimental bronchial spasm development, the ratios of SMC in bronchial SMT are changed with the increase in proportion of small SMC and the elimination of large SMC. In the dynamics of experimental bronchial spasm development, the activation of cytoplasmic synthesis as well as of DNA synthesis was detected mainly in group of small SMC. The reactive-dystrophic changes were marked at the subcellular level, that were most often identified in large SMC resulting in their elimination from population in the dynamics of an experiment. The data obtained suggest that one of the important mechanisms of airway SMT adaptation to the bronchial spasm development is a dynamic reorganization of SMC population.

  15. Eosinophil cationic protein mRNA expression in children with bronchial asthma.

    Science.gov (United States)

    Yu, H Y; Li, X Y; Cai, Z F; Li, L; Shi, X Z; Song, H X; Liu, X J

    2015-11-13

    Studies have shown that eosinophils are closely related to pathogenesis of bronchial asthma. Eosinophils release eosinophil cationic protein (ECP), which plays an important role in infection and allergic reactions. Serum ECP mRNA expression in children with bronchial asthma has not been adequately investigated. We analyzed serum ECP mRNA expression in 63 children with bronchial asthma and 21 healthy children by using reverse-transcriptase polymerase chain reaction to understand the role of ECP in children with bronchial asthma. The children with bronchial asthma were segregated into acute-phase and stable-phase groups, based on the severity of the illness. Serum ECP mRNA expression in children with bronchial asthma (0.375 ± 0.04) was significantly higher than that in healthy controls (0.20 ± 0.02; P children in the acute-phase group showed higher ECP mRNA expression level (0.44 ± 0.06) than those in the stable-phase (0.31 ± 0.03) and healthy control groups (0.20 ± 0.02; P children with bronchial asthma.

  16. [Morpho-functional characteristics of the lingual epithelium after administration of hydra peptide morphogen].

    Science.gov (United States)

    Kulaeva, V V; Bykov, V L

    2007-01-01

    Using histological, morphometric and quantitative histoenzymological methods, the changes of lingual epithelium were studied in 40 outbred albino mice after 5 intraperitoneal injections of 100 micrograms of hydra peptide morphogen (HPM) per 1 kg of body weight. Administration of HPM was found to increase the total thickness of epithelial layer on the dorsal tongue surface in the interpapillary regions, while in the area of filiform papillae these changes were not significant. On the ventral tongue surface HPM induced a marked increase of total thickness of the epithelial layer as compared to that in control animals. Mitotic activity was increased in the epithelium covering the ventral surface and in the interpapillary regions on the dorsal tongue surface. Histoenzymologic study which involved the demonstration of NADH-diaphorase, succinate- and lactate-dehydrogenase (LDH) activities, followed by a cytophotometric evaluation of enzyme activity, has shown a stimulatory effect of HPM on the activity of all the enzymes studied, which was most pronounced in respect to LDH and was maximally expressed on the dorsal tongue surface. These findings collectively suggest that HPM exerts a stimulatory effect on proliferation activity and metabolism of lingual epithelium, which is differentially expressed in its variuoe topographical zones.

  17. Neuropilin 1 Receptor Is Up-Regulated in Dysplastic Epithelium and Oral Squamous Cell Carcinoma

    Science.gov (United States)

    Shahrabi-Farahani, Shokoufeh; Gallottini, Marina; Martins, Fabiana; Li, Erik; Mudge, Dayna R.; Nakayama, Hironao; Hida, Kyoko; Panigrahy, Dipak; D'Amore, Patricia A.; Bielenberg, Diane R.

    2017-01-01

    Neuropilins are receptors for disparate ligands, including proangiogenic factors such as vascular endothelial growth factor and inhibitory class 3 semaphorin (SEMA3) family members. Differentiated cells in skin epithelium and cutaneous squamous cell carcinoma highly express the neuropilin-1 (NRP1) receptor. We examined the expression of NRP1 in human and mouse oral mucosa. NRP1 was significantly up-regulated in oral epithelial dysplasia and oral squamous cell carcinoma (OSCC). NRP1 receptor localized to the outer suprabasal epithelial layers in normal tongue, an expression pattern similar to the normal skin epidermis. However, dysplastic tongue epithelium and OSCC up-regulated NRP1 in basal and proliferating epithelial layers, a profile unseen in cutaneous squamous cell carcinoma. NRP1 up-regulation is observed in a mouse carcinogen-induced OSCC model and in human tongue OSCC biopsies. Human OSCC cell lines express NRP1 protein in vitro and in mouse tongue xenografts. Sites of capillary infiltration into orthotopic OSCC tumors correlate with high NRP1 expression. HSC3 xenografts, which express the highest NRP1 levels of the cell lines examined, showed massive intratumoral lymphangiogenesis. SEMA3A inhibited OSCC cell migration, suggesting that the NRP1 receptor was bioactive in OSCC. In conclusion, NRP1 is regulated in the oral epithelium and is selectively up-regulated during epithelial dysplasia. NRP1 may function as a reservoir to sequester proangiogenic ligands within the neoplastic compartment, thereby recruiting neovessels toward tumor cells. PMID:26877262

  18. Electrophysiological response of chicken's jejunal epithelium to increasing levels of T-2 toxin.

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    Yunus, Agha Waqar; Kröger, Susan; Tichy, Alexander; Zentek, Jürgen; Böhm, Josef

    2013-02-01

    The present investigations were conducted to test the effects of T-2 toxin on electrophysiological variables of jejunal epithelium of chicken. Jejunal segments of broilers were monitored in Ussing chambers in the presence of T-2 toxin at the levels of 0 (negative control), 0 (methanol/vehicle control), 0.1, 1, 5, and 10 μg/ml of buffer. T-2 toxin did not affect basal values of short circuit current (I(sc)), transmural potential difference, or tissue conductivity in the jejunal epithelium. T-2 toxin also did not statistically affect glucose-induced electrophysiological variables during the first 3 min of glucose induction. Compared to the vehicle control, the ouabain-sensitive I(sc) was negatively affected (P = 0.008) only under 5 μg of T-2 toxin/ml. Increasing levels of T-2 toxin negatively affected the ouabain-sensitive I(sc) in a cubic (P = 0.007) fashion. These data indicate that acute exposure to moderate levels of T-2 toxin may progressively impair the cation gradient across the jejunal epithelium.

  19. Generation of human female reproductive tract epithelium from human embryonic stem cells.

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    Louie Ye

    Full Text Available BACKGROUND: Recent studies have identified stem/progenitor cells in human and mouse uterine epithelium, which are postulated to be responsible for tissue regeneration and proliferative disorders of human endometrium. These progenitor cells are thought to be derived from Müllerian duct (MD, the primordial female reproductive tract (FRT. METHODOLOGY/PRINCIPAL FINDINGS: We have developed a model of human reproductive tract development in which inductive neonatal mouse uterine mesenchyme (nMUM is recombined with green fluorescent protein (GFP-tagged human embryonic stem cells (hESCs; GFP-hESC (ENVY. We demonstrate for the first time that hESCs can be differentiated into cells with a human FRT epithelial cell phenotype. hESC derived FRT epithelial cells emerged from cultures containing MIXL1(+ mesendodermal precursors, paralleling events occurring during normal organogenesis. Following transplantation, nMUM treated embryoid bodies (EBs generated epithelial structures with a typical MD phenotype that expressed the MD markers PAX2, HOXA10. Functionally, the hESCs derived FRT epithelium responded to exogenous estrogen by proliferating and secreting uterine-specific glycodelin A (GdA. CONCLUSIONS/SIGNIFICANCE: These data show nMUM can induce differentiation of hESC to form the FRT epithelium. This may provide a model to study early developmental events of the human FRT.

  20. Maintenance of sweat glands by stem cells located in the acral epithelium.

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    Ohe, Shuichi; Tanaka, Toshihiro; Yanai, Hirotsugu; Komai, Yoshihiro; Omachi, Taichi; Kanno, Shohei; Tanaka, Kiyomichi; Ishigaki, Kazuhiko; Saiga, Kazuho; Nakamura, Naohiro; Ohsugi, Haruyuki; Tokuyama, Yoko; Atsumi, Naho; Hisha, Hiroko; Yoshida, Naoko; Kumano, Keiki; Yamazaki, Fumikazu; Okamoto, Hiroyuki; Ueno, Hiroo

    2015-10-23

    The skin is responsible for a variety of physiological functions and is critical for wound healing and repair. Therefore, the regenerative capacity of the skin is important. However, stem cells responsible for maintaining the acral epithelium had not previously been identified. In this study, we identified the specific stem cells in the acral epithelium that participate in the long-term maintenance of sweat glands, ducts, and interadnexal epidermis and that facilitate the regeneration of these structures following injury. Lgr6-positive cells and Bmi1-positive cells were found to function as long-term multipotent stem cells that maintained the entire eccrine unit and the interadnexal epidermis. However, while Lgr6-positive cells were rapidly cycled and constantly supplied differentiated cells, Bmi1-positive cells were slow to cycle and occasionally entered the cell cycle under physiological conditions. Upon irradiation-induced injury, Bmi1-positive cells rapidly proliferated and regenerated injured epithelial tissue. Therefore, Bmi1-positive stem cells served as reservoir stem cells. Lgr5-positive cells were rapidly cycled and maintained only sweat glands; therefore, we concluded that these cells functioned as lineage-restricted progenitors. Taken together, our data demonstrated the identification of stem cells that maintained the entire acral epithelium and supported the different roles of three cellular classes.

  1. Neuropilin 1 Receptor Is Up-Regulated in Dysplastic Epithelium and Oral Squamous Cell Carcinoma.

    Science.gov (United States)

    Shahrabi-Farahani, Shokoufeh; Gallottini, Marina; Martins, Fabiana; Li, Erik; Mudge, Dayna R; Nakayama, Hironao; Hida, Kyoko; Panigrahy, Dipak; D'Amore, Patricia A; Bielenberg, Diane R

    2016-04-01

    Neuropilins are receptors for disparate ligands, including proangiogenic factors such as vascular endothelial growth factor and inhibitory class 3 semaphorin (SEMA3) family members. Differentiated cells in skin epithelium and cutaneous squamous cell carcinoma highly express the neuropilin-1 (NRP1) receptor. We examined the expression of NRP1 in human and mouse oral mucosa. NRP1 was significantly up-regulated in oral epithelial dysplasia and oral squamous cell carcinoma (OSCC). NRP1 receptor localized to the outer suprabasal epithelial layers in normal tongue, an expression pattern similar to the normal skin epidermis. However, dysplastic tongue epithelium and OSCC up-regulated NRP1 in basal and proliferating epithelial layers, a profile unseen in cutaneous squamous cell carcinoma. NRP1 up-regulation is observed in a mouse carcinogen-induced OSCC model and in human tongue OSCC biopsies. Human OSCC cell lines express NRP1 protein in vitro and in mouse tongue xenografts. Sites of capillary infiltration into orthotopic OSCC tumors correlate with high NRP1 expression. HSC3 xenografts, which express the highest NRP1 levels of the cell lines examined, showed massive intratumoral lymphangiogenesis. SEMA3A inhibited OSCC cell migration, suggesting that the NRP1 receptor was bioactive in OSCC. In conclusion, NRP1 is regulated in the oral epithelium and is selectively up-regulated during epithelial dysplasia. NRP1 may function as a reservoir to sequester proangiogenic ligands within the neoplastic compartment, thereby recruiting neovessels toward tumor cells.

  2. Annexin A2 Acts as an Adhesion Molecule on the Endometrial Epithelium during Implantation in Mice.

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    Wang, Bing; Ye, Tian-Min; Lee, Kai-Fai; Chiu, Philip C N; Pang, Ronald T K; Ng, Ernest H Y; Yeung, William S B

    2015-01-01

    To determine the function of Annexin A2 (Axna2) in mouse embryo implantation in vivo, experimental manipulation of Axna2 activities was performed in mouse endometrial tissue in vivo and in vitro. Histological examination of endometrial tissues was performed throughout the reproduction cycle and after steroid treatment. Embryo implantation was determined after blockage of the Axna2 activities by siRNA or anti-Axna2 antibody. The expression of Axna2 immunoreactivies in the endometrial luminal epithelium changed cyclically in the estrus cycle and was upregulated by estrogen. After nidatory estrogen surge, there was a concentration of Axna2 immunoreactivities at the interface between the implanting embryo and the luminal epithelium. The phenomenon was likely to be induced by the implanting embryos as no such concentration of signal was observed in the inter-implantation sites and in pseudopregnancy. Knockdown of Axna2 by siRNA reduced attachment of mouse blastocysts onto endometrial tissues in vitro. Consistently, the number of implantation sites was significantly reduced after infusion of anti-Axna2 antibody into the uterine cavity. Steroids and embryos modulate the expression of Axna2 in the endometrial epithelium. Axna2 may function as an adhesion molecule during embryo implantation in mice.

  3. Eya1 protein phosphatase regulates tight junction formation in lung distal epithelium.

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    El-Hashash, Ahmed H K; Turcatel, Gianluca; Varma, Saaket; Berika, Mohamed; Al Alam, Denise; Warburton, David

    2012-09-01

    Little is known about the regulatory mechanisms underlying lung epithelial tight junction (TJ) assembly, which is inextricably linked to the preservation of epithelial polarity, and is highly coordinated by proteins that regulate epithelial cell polarity, such as aPKCζ. We recently reported that Eya1 phosphatase functions through aPKCζ-Notch1 signaling to control cell polarity in the lung epithelium. Here, we have extended these observations to TJ formation to demonstrate that Eya1 is crucial for the maintenance of TJ protein assembly in the lung epithelium, probably by controlling aPKCζ phosphorylation levels, aPKCζ-mediated TJ protein phosphorylation and Notch1-Cdc42 activity. Thus, TJs are disassembled after interfering with Eya1 function in vivo or during calcium-induced TJ assembly in vitro. These effects are reversed by reintroduction of wild-type Eya1 or partially inhibiting aPKCζ in Eya1siRNA cells. Moreover, genetic activation of Notch1 rescues Eya1(-/-) lung epithelial TJ defects. These findings uncover novel functions for the Eya1-aPKCζ-Notch1-Cdc42 pathway as a crucial regulatory mechanism of TJ assembly and polarity of the lung epithelium, providing a conceptual framework for future mechanistic and translational studies in this area.

  4. Scanning electron microscopic studies of the surface morphology of the vomeronasal epithelium and olfactory epithelium of garter snakes.

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    Wang, R T; Halpern, M

    1980-04-01

    Fixed vomeronasal and olfactory epithelia from normal adult garter snakes were microdissected, fractured, and examined with a scanning electron microscope. The method permits a detailed comparative study of the structural organization and morphological characteristics of the constituent cells of the vomeronasal and olfactory epithelia. Despite similarities in the nomenclature of the constituent cells in both epithelia, significant differences exist in their surface morphology. A unique columnar structure composed of non-neuronal elements is present in the vomeronasal epithelium. These columns house the bioplar neurons and undifferentiated cells. Such a columnar organization is absent in the olfactory epithelium. In vomeronasal epithelium the bipolar neurons possess microvillous terminals at their dendritic tips, while the dendritic tips of the bipolar neurons of the olfactory epithelium possess cilia. Vomeronasal supporting cells are covered with microvilli, while olfactory supporting cells are covered with cytoplasmic protuberances in addition to the microvilli. In the vomeronasal epithelium the pear-shaped neurons have a grossly smooth surface and are organized into clusters, while in the olfactory epithelium the elliptical bipolar neurons are spinous, aligned side-by-side and interdigitate. The basal (undifferentiated) cell layer in the vomeronasal epithelium has a high packing density and is composed of several layers of irregularly shaped cells. In the olfactory epithelium the basal cell layer is loosely organized and composed of a single layer of oval cells. This information on the three-dimensional cell structure of both epithelia provides a basis for experimental observations on changes in morphology of the bipolar neurons during genesis, development, maturation, degeneration, and regeneration in postnatal, adult animals.

  5. Molecular Mechanisms of Malignant Transformation by Low Dose Cadmium in Normal Human Bronchial Epithelial Cells.

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    Laura Cartularo

    Full Text Available Cadmium is a carcinogenic metal, the mechanisms of which are not fully understood. In this study, human bronchial epithelial cells were transformed with sub-toxic doses of cadmium (0.01, 0.05, and 0.1 μM and transformed clones were characterized for gene expression changes using RNA-seq, as well as other molecular measurements. 440 genes were upregulated and 47 genes were downregulated in cadmium clones relative to control clones over 1.25-fold. Upregulated genes were associated mostly with gene ontology terms related to embryonic development, immune response, and cell movement, while downregulated genes were associated with RNA metabolism and regulation of transcription. Several embryonic genes were upregulated, including the transcription regulator SATB2. SATB2 is critical for normal skeletal development and has roles in gene expression regulation and chromatin remodeling. Small hairpin RNA knockdown of SATB2 significantly inhibited growth in soft agar, indicating its potential as a driver of metal-induced carcinogenesis. An increase in oxidative stress and autophagy was observed in cadmium clones. In addition, the DNA repair protein O6-methylguanine-DNA-methyltransferase was depleted by transformation with cadmium. MGMT loss caused significant decrease in cell viability after treatment with the alkylating agent temozolomide, demonstrating diminished capacity to repair such damage. Results reveal various mechanisms of cadmium-induced malignant transformation in BEAS-2B cells including upregulation of SATB2, downregulation of MGMT, and increased oxidative stress.

  6. Anti-inflammatory effects of antibacterials on human bronchial epithelial cells

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    Hatz Rudolf

    2009-09-01

    Full Text Available Abstract Background Human Bronchial epithelial cells (hu-BEC have been claimed to play a significant role in the pathogenesis of chronic inflammatory airway diseases like COPD. In this context IL-8 and GM-CSF have been shown to be key cytokines. Some antibiotics which are routinely used to treat lower respiratory tract infections have been shown to exert additional immunomodulatory or anti-inflammatory effects. We investigated whether these effects can also be detected in hu-BEC. Methods Hu-BEC obtained from patients undergoing lung resections were transferred to air-liquid-interface (ALI culture. These cultures were incubated with cefuroxime (CXM, 10-62.5 mg/l, azithromycin (AZM, 0.1-1.5 mg/l, levofloxacin (LVX, 1-8 mg/l and moxifloxacin (MXF, 1-16 mg/l. The spontaneous and TNF-α (10 ng/ml induced expression and release of IL-8 and GM-CSF were measured using PCR and ELISA in the absence or presence of these antibiotics. Results The spontaneous IL-8 and GM-CSF release was significantly reduced with MXF (8 mg/l by 37 ± 20% and 45 ± 31%, respectively (both p Conclusion Using ALI cultures of hu-BEC we observed differential effects of antibiotics on spontaneous and TNF-α induced cytokine release. Our data suggest that MXF and AZM, beyond bactericidal effects, may attenuate the inflammatory process mediated by hu-BEC.

  7. Eicosanoid biosynthesis during mucociliary and mucous metaplastic differentiation of bronchial epithelial cells.

    Science.gov (United States)

    Jakiela, Bogdan; Gielicz, Anna; Plutecka, Hanna; Hubalewska, Magdalena; Mastalerz, Lucyna; Bochenek, Grazyna; Soja, Jerzy; Januszek, Rafal; Musial, Jacek; Sanak, Marek

    2013-10-01

    The purpose of this study was to examine the profile of eicosanoids secreted by human bronchial epithelial cells (HBEC) during their in vitro differentiation toward mucociliary or mucous metaplastic phenotype. Eicosanoids were measured in supernatants by mass spectrometry, and corresponding gene expression by real-time PCR. Primary HBEC produced mainly prostaglandins (PGE2, PGD2) and epoxides (e.g. 14,15-EET), but during further mucociliary differentiation we observed a gradual increase in secretion of lipoxygenase derived HETEs. Treatment with IL-13 and IL-4 induced mucous metaplasia and resulted in downregulation of PG pathway, and potent induction of 15-lipoxygenase (marked release of 15-HETE). The deficiency in PG production sustained during long term culture of mucous metaplastic epithelia. In conclusions, Th2-type cytokines induce changes in eicosanoid metabolism of airway epithelial cells, resulting in an immense induction of 15-lipoxygenase pathway, and inhibition of PG pathways. Deficient production of immunomodulatory PGs may promote chronic inflammation and airway remodeling.

  8. Antioxidant ability and radiosensitivity in malignant transformed human bronchial epithelial cell line BEP2D induced by α-particle irradiation%α粒子诱发BEP2D细胞恶性转化中抗氧化能力和辐射敏感性研究

    Institute of Scientific and Technical Information of China (English)

    苟巧; 张伟; 王春燕; 苏旭

    2011-01-01

    Objective To investigate the antioxidant ability and radiosensitivity in the malignant transformed human bronchial epithelial cell line BEP2D induced by α-particle exposure.Methods Glutathione Peroxidase (GPX),Catalase (CAT) and Glutathione (GSH) assay kits were employed to detect GPX and CAT enzyme abilities and the levels of GSH in BEP2D,RH21 ( passage 21 of α-particle-irradiated BEP2D cells),and BERP35T-1 cells (derived from nude mice bearing malignant transformed cells generated from cells of passage 35 of α-particle-irradiated BEP2D cells).MTT assay were used to test the growth rate of BEP2D,RH21 and BERP35T-1 cells treated with 0,30,60,90,120,and 150 μmoL/L H2O2.Colony-forming test and MTT assay were used to examine the cell survival fraction and the growth rate of BEP2D,RH21 and BERP35T-1 cells exposed to 0,2,4,and 8 Gy of γ-rays,respectively.Results GPX and CAT enzyme activities in RH21 and BERP35T-1 cells were obviously lower than in BEP2D( t = 5.75-67.92 ,P < 0.05 ).CAT enzyme activity in BERP35T-1 was lower than that in RH21 cells (t =22.25 ,P <0.01 ).Compared to BEP2D cells,decreased level of GSH was detected in BERP35T-1 cells(t = 7.76,P < 0.05 ),but there was no change in RH21.After treatment with 30,60,90,120,and 150 μmol/L H2O2,the growth rates of BEP2D were all higher than those of BERP35T-1 cells(t = 10.37-58.36,P <0.01 ).Meanwhile,the growth rates of BEP2D were all higher than those of RH21 cells after treatment with 60,90,120,and 150 μ mol/L H2O2 (t = 29.90-84.68,P < 0.01 ).In addition,compared to BEP2D cells,decreased cell survival fraction and growth rate of BERP35T-1 cells were observed after irradiation with 2,4,and 8 Gy of y-rays ( t = 5.87-34.17,P < 0.05 ).The cell survival fraction and growth rate of RH21 were all lower than those of BEP2D cells at 4 and 8 Gy post-irradition( t =6.33- 45.00,P < 0.05 ).Conclusion The function of antioxidant system decreased in the α-particleinduced transformed cells,which could

  9. The octopamine receptor OAMB mediates ovulation via Ca2+/calmodulin-dependent protein kinase II in the Drosophila oviduct epithelium.

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    Hyun-Gwan Lee

    Full Text Available Ovulation is an essential physiological process in sexual reproduction; however, the underlying cellular mechanisms are poorly understood. We have previously shown that OAMB, a Drosophila G-protein-coupled receptor for octopamine (the insect counterpart of mammalian norepinephrine, is required for ovulation induced upon mating. OAMB is expressed in the nervous and reproductive systems and has two isoforms (OAMB-AS and OAMB-K3 with distinct capacities to increase intracellular Ca2+ or intracellular Ca2+ and cAMP in vitro. Here, we investigated tissue specificity and intracellular signals required for OAMB's function in ovulation. Restricted OAMB expression in the adult oviduct epithelium, but not the nervous system, reinstated ovulation in oamb mutant females, in which either OAMB isoform was sufficient for the rescue. Consistently, strong immunoreactivities for both isoforms were observed in the wild-type oviduct epithelium. To delineate the cellular mechanism by which OAMB regulates ovulation, we explored protein kinases functionally interacting with OAMB by employing a new GAL4 driver with restricted expression in the oviduct epithelium. Conditional inhibition of Ca2+/Calmodulin-dependent protein kinase II (CaMKII, but not protein kinase A or C, in the oviduct epithelium inhibited ovulation. Moreover, constitutively active CaMKII, but not protein kinase A, expressed only in the adult oviduct epithelium fully rescued the oamb female's phenotype, demonstrating CaMKII as a major downstream molecule conveying the OAMB's ovulation signal. This is consistent with the ability of both OAMB isoforms, whose common intracellular signal in vitro is Ca2+, to reinstate ovulation in oamb females. These observations reveal the critical roles of the oviduct epithelium and its cellular components OAMB and CaMKII in ovulation. It is conceivable that the OAMB-mediated cellular activities stimulated upon mating are crucial for secretory activities suitable for egg

  10. Sox9 drives columnar differentiation of esophageal squamous epithelium: a possible role in the pathogenesis of Barrett's esophagus.

    Science.gov (United States)

    Clemons, Nicholas J; Wang, David H; Croagh, Daniel; Tikoo, Anjali; Fennell, Christina M; Murone, Carmel; Scott, Andrew M; Watkins, D Neil; Phillips, Wayne A

    2012-12-15

    The molecular mechanism underlying the development of Barrett's esophagus (BE), the precursor to esophageal adenocarcinoma, remains unknown. Our previous work implicated sonic hedgehog (Shh) signaling as a possible driver of BE and suggested that bone morphogenetic protein 4 (Bmp4) and Sox9 were downstream mediators. We have utilized a novel in vivo tissue reconstitution model to investigate the relative roles of Bmp4 and Sox9 in driving metaplasia. Epithelia reconstituted from squamous epithelial cells or empty vector-transduced cells had a stratified squamous phenotype, reminiscent of normal esophagus. Expression of Bmp4 in the stromal compartment activated signaling in the epithelium but did not alter the squamous phenotype. In contrast, expression of Sox9 in squamous epithelial cells induced formation of columnar-like epithelium with expression of the columnar differentiation marker cytokeratin 8 and the intestinal-specific glycoprotein A33. In patient tissue, A33 protein was expressed specifically in BE, but not in normal esophagus. Expression of Cdx2, another putative driver of BE, alone had no effect on reconstitution of a squamous epithelium. Furthermore, epithelium coexpressing Cdx2 and Sox9 had a phenotype similar to epithelium expressing Sox9 alone. Our results demonstrate that Sox9 is sufficient to drive columnar differentiation of squamous epithelium and expression of an intestinal differentiation marker, reminiscent of BE. These data suggest that Shh-mediated expression of Sox9 may be an important early event in the development of BE and that the potential for inhibitors of the hedgehog pathway to be used in the treatment of BE and/or esophageal adenocarcinoma could be tested in the near future.

  11. Telomere shortening impairs regeneration of the olfactory