المؤلفون: Engle, Michelle L., Monk, Justine N., Jania, Corey M., Martin, Jessica R., Gomez, John C., Dang, Hong, Parker, Joel S., Doerschuk, Claire M.

المصدر: PLoS ONE; 2/28/2019, Vol. 14 Issue 2, p1-37, 37p

مصطلحات موضوعية: CIGARETTE smoke, LUNG injuries, MESSENGER RNA, EXTRACELLULAR matrix, CHRONIC bronchitis, OXIDATIVE stress

مستخلص: Cigarette smoke is well recognized to cause injury to the airways and the alveolar walls over time. This injury usually requires many years of exposure, suggesting that the lungs may rapidly develop responses that initially protect it from this repetitive injury. Our studies tested the hypotheses that smoke induces an inflammatory response and changes in mRNA profiles that are dependent on sex and the health status of the lung, and that the response of the lungs to smoke differs after 1 day compared to 5 days of exposure. Male and female wildtype (WT) and Scnn1b-transgenic (βENaC) mice, which have chronic bronchitis and emphysematous changes due to dehydrated mucus, were exposed to cigarette smoke or sham air conditions for 1 or 5 days. The inflammatory response and gene expression profiles were analyzed in lung tissue. Overall, the inflammatory response to cigarette smoke was mild, and changes in mediators were more numerous after 1 than 5 days. βENaC mice had more airspace leukocytes than WT mice, and smoke exposure resulted in additional significant alterations. Many genes and gene sets responded similarly at 1 and 5 days: genes involved in oxidative stress responses were upregulated while immune response genes were downregulated. However, certain genes and biological processes were regulated differently after 1 compared to 5 days. Extracellular matrix biology genes and gene sets were upregulated after 1 day but downregulated by 5 days of smoke compared to sham exposure. There was no difference in the transcriptional response to smoke between WT and βENaC mice or between male and female mice at either 1 or 5 days. Taken together, these studies suggest that the lungs rapidly alter gene expression after only one exposure to cigarette smoke, with few additional changes after four additional days of repeated exposure. These changes may contribute to preventing lung damage. [ABSTRACT FROM AUTHOR]

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المؤلفون: Li, Jianping, Helal, Zeinab H., Karch, Christopher P., Mishra, Neha, Girshick, Theodore, Garmendia, Antonio, Burkhard, Peter, Khan, Mazhar I.

المصدر: PLoS ONE; 9/14/2018, Vol. 13 Issue 9, p1-17, 17p

مصطلحات موضوعية: AVIAN infectious bronchitis virus, VIRAL vaccines, B cells, PROTEINS, FLAGELLIN

مستخلص: Infectious bronchitis virus (IBV) affects poultry respiratory, renal and reproductive systems. Currently the efficacy of available live attenuated or killed vaccines against IBV has been challenged. We designed a novel IBV vaccine alternative using a highly innovative platform called Self-Assembling Protein Nanoparticle (SAPN). In this vaccine, B cell epitopes derived from the second heptad repeat (HR2) region of IBV spike proteins were repetitively presented in its native trimeric conformation. In addition, flagellin was co-displayed in the SAPN to achieve a self-adjuvanted effect. Three groups of chickens were immunized at four weeks of age with the vaccine prototype, IBV-Flagellin-SAPN, a negative-control construct Flagellin-SAPN or a buffer control. The immunized chickens were challenged with 5x10^4.7 EID50 IBV M41 strain. High antibody responses were detected in chickens immunized with IBV-Flagellin-SAPN. In ex vivo proliferation tests, peripheral mononuclear cells (PBMCs) derived from IBV-Flagellin-SAPN immunized chickens had a significantly higher stimulation index than that of PBMCs from chickens receiving Flagellin-SAPN. Chickens immunized with IBV-Flagellin-SAPN had a significant reduction of tracheal virus shedding and lesser tracheal lesion scores than did negative control chickens. The data demonstrated that the IBV-Flagellin-SAPN holds promise as a vaccine for IBV. [ABSTRACT FROM AUTHOR]

: Copyright of PLoS ONE is the property of Public Library of Science and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

المؤلفون: Einsiedel, Lloyd, Pham, Hai, Wilson, Kim, Walley, Rebecca, Turpin, Jocelyn, Bangham, Charles, Gessain, Antoine, Woodman, Richard J.

المصدر: PLoS Neglected Tropical Diseases; 3/12/2018, Vol. 12 Issue 3, p1-17, 17p

مصطلحات موضوعية: HIV, VIRAL load, LUNG diseases, INDIGENOUS Australians, INFLAMMATION, BRONCHITIS, HEALTH of indigenous peoples

مستخلص: Background: The Human T-Lymphotropic Virus type 1c subtype (HTLV-1c) is highly endemic to central Australia where the most frequent complication of HTLV-1 infection in Indigenous Australians is bronchiectasis. We carried out a prospective study to quantify the prognosis of HTLV-1c infection and chronic lung disease and the risk of death according to the HTLV-1c proviral load (pVL). Methodology/Principal findings: 840 Indigenous adults (discharge diagnosis of bronchiectasis, 154) were recruited to a hospital-based prospective cohort. Baseline HTLV-1c pVL were determined and the results of chest computed tomography and clinical details reviewed. The odds of an association between HTLV-1 infection and bronchiectasis or bronchitis/bronchiolitis were calculated, and the impact of HTLV-1c pVL on the risk of death was measured. Radiologically defined bronchiectasis and bronchitis/bronchiolitis were significantly more common among HTLV-1-infected subjects (adjusted odds ratio = 2.9; 95% CI, 2.0, 4.3). Median HTLV-1c pVL for subjects with airways inflammation was 16-fold higher than that of asymptomatic subjects. There were 151 deaths during 2,140 person-years of follow-up (maximum follow-up 8.13 years). Mortality rates were higher among subjects with HTLV-1c pVL ≥1000 copies per 10⁵ peripheral blood leukocytes (log-rank χ² (2df) = 6.63, p = 0.036) compared to those with lower HTLV-1c pVL or uninfected subjects. Excess mortality was largely due to bronchiectasis-related deaths (adjusted HR 4.31; 95% CI, 1.78, 10.42 versus uninfected). Conclusion/Significance: Higher HTLV-1c pVL was strongly associated with radiologically defined airways inflammation and with death due to complications of bronchiectasis. An increased risk of death due to an HTLV-1 associated inflammatory disease has not been demonstrated previously. Our findings indicate that mortality associated with HTLV-1c infection may be higher than has been previously appreciated. Further prospective studies are needed to determine whether these results can be generalized to other HTLV-1 endemic areas. [ABSTRACT FROM AUTHOR]

: Copyright of PLoS Neglected Tropical Diseases is the property of Public Library of Science and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

المؤلفون: Amarasinghe, Aruna, Abdul-Cader, Mohamed Sarjoon, Nazir, Sadiya, De Silva Senapathi, Upasama, van der Meer, Frank, Cork, Susan Catherine, Gomis, Susantha, Abdul-Careem, Mohamed Faizal

المصدر: PLoS ONE; 8/1/2017, Vol. 12 Issue 8, p1-21, 21p

مصطلحات موضوعية: AVIAN infectious bronchitis, MACROPHAGES, VETERINARY medicine, ANTI-infective agents, VIRAL replication, MEDICAL microbiology

مستخلص: Infectious bronchitis virus (IBV) causes respiratory disease leading to loss of egg and meat production in chickens. Although it is known that macrophage numbers are elevated in the respiratory tract of IBV infected chickens, the role played by macrophages in IBV infection, particularly as a target cell for viral replication, is unknown. In this study, first, we investigated the ability of IBV to establish productive replication in macrophages in lungs and trachea in vivo and in macrophage cell cultures in vitro using two pathogenic IBV strains. Using a double immunofluorescent technique, we observed that both IBV Massachusetts-type 41 (M41) and Connecticut A5968 (Conn A5968) strains replicate in avian macrophages at a low level in vivo. This in vivo observation was substantiated by demonstrating IBV antigens in macrophages following in vitro IBV infection. Further, IBV productive infection in macrophages was confirmed by demonstrating corona viral particles in macrophages and IBV ribonucleic acid (RNA) in culture supernatants. Evaluation of the functions of macrophages following infection of macrophages with IBV M41 and Conn A5968 strains revealed that the production of antimicrobial molecule, nitric oxide (NO) is inhibited. It was also noted that replication of IBV M41 and Conn A5968 strains in macrophages does not interfere with the induction of type 1 IFN activity by macrophages. In conclusion, both M41 and Con A5968 IBV strains infect macrophages in vivo and in vitro resulting productive replications. During the replication of IBV in macrophages, their ability to produce NO can be affected without affecting the ability to induce type 1 IFN activity. Further studies are warranted to uncover the significance of macrophage infection of IBV in the pathogenesis of IBV infection in chickens. [ABSTRACT FROM AUTHOR]

: Copyright of PLoS ONE is the property of Public Library of Science and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

المؤلفون: Okino, Cintia Hiromi, Mores, Marcos Antônio Zanella, Trevisol, Iara Maria, Coldebella, Arlei, Montassier, Hélio José, Brentano, Liana

المصدر: PLoS ONE; 2/15/2017, Vol. 12 Issue 2, p1-17, 17p

مصطلحات موضوعية: IMMUNE response, AVIAN infectious bronchitis virus, VIRUS virulence, EPITHELIAL cells, GENE expression

مستخلص: Avian infectious bronchitis virus (IBV) primarily replicates in epithelial cells of the upper respiratory tract of chickens, inducing both morphological and immune modulatory changes. However, the association between the local immune responses induced by IBV and the mechanisms of pathogenesis has not yet been completely elucidated. This study compared the expression profile of genes related to immune responses in tracheal samples after challenge with two Brazilian field isolates (A and B) of IBV from the same genotype, associating these responses with viral replication and with pathological changes in trachea and kidney. We detected a suppressive effect on the early activation of TLR7 pathway, followed by lower expression levels of inflammatory related genes induced by challenge with the IBV B isolate when compared to the challenge with to the IBV A isolate. Cell-mediated immune (CMI) related genes presented also lower levels of expression in tracheal samples from birds challenged with B isolate at 1dpi. Increased viral load and a higher percentage of birds with relevant lesions were observed in both tracheal and renal samples from chickens exposed to challenge with IBV B isolate. This differential pattern of early immune responses developed after challenge with IBV B isolate, related to the downregulation of TLR7, leading to insufficient pro-inflammatory response and lower CMI responses, seem to have an association with a most severe renal lesion and an enhanced capability of replication of this isolate in chicken. [ABSTRACT FROM AUTHOR]

: Copyright of PLoS ONE is the property of Public Library of Science and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

المؤلفون: Simpson, Jodie L., Powell, Heather, Baines, Katherine J., Milne, David, Coxson, Harvey O., Hansbro, Philip M., Gibson, Peter G.

المصدر: PLoS ONE; Aug2014, Vol. 9 Issue 8, p1-10, 10p

مصطلحات موضوعية: NEUTROPHILS, AZITHROMYCIN, OBSTRUCTIVE lung disease treatment, PLACEBOS, DISEASE progression, AIRWAY (Anatomy), BRONCHITIS, THERAPEUTICS

مستخلص: Background: Chronic Obstructive Pulmonary Disease (COPD) is a progressive airway disease characterised by neutrophilic airway inflammation or bronchitis. Neutrophilic bronchitis is associated with both bacterial colonisation and lung function decline and is common in exacerbations of COPD. Despite current available therapies to control inflammation, neutrophilic bronchitis remains common. This study tested the hypothesis that azithromycin treatment, as an add-on to standard medication, would significantly reduce airway neutrophil and neutrophils chemokine (CXCL8) levels, as well as bacterial load. We conducted a randomised, double-blind, placebo-controlled study in COPD participants with stable neutrophilic bronchitis. Methods: Eligible participants (n = 30) were randomised to azithromycin 250 mg daily or placebo for 12 weeks in addition to their standard respiratory medications. Sputum was induced at screening, randomisation and monthly for a 12 week treatment period and processed for differential cell counts, CXCL8 and neutrophil elastase assessment. Quantitative bacteriology was assessed in sputum samples at randomisation and the end of treatment visit. Severe exacerbations where symptoms increased requiring unscheduled treatment were recorded during the 12 week treatment period and for 14 weeks following treatment. A sub-group of participants underwent chest computed tomography scans (n = 15). Results: Nine participants with neutrophilic bronchitis had a potentially pathogenic bacteria isolated and the median total bacterial load of all participants was 5.22×10⁷ cfu/mL. Azithromycin treatment resulted in a non-significant reduction in sputum neutrophil proportion, CXCL8 levels and bacterial load. The mean severe exacerbation rate was 0.33 per person per 26 weeks in the azithromycin group compared to 0.93 exacerbations per person in the placebo group (incidence rate ratio (95%CI): 0.37 (0.11,1.21), p = 0.062). For participants who underwent chest CT scans, no alterations were observed. Conclusions: In stable COPD with neutrophilic bronchitis, add-on azithromycin therapy showed a trend to reduced severe exacerbations sputum neutrophils, CXCL8 levels and bacterial load. Future studies with a larger sample size are warranted. Trial Registration: Australian New Zealand Clinical Trials Registry ACTRN12609000259246 [ABSTRACT FROM AUTHOR]

: Copyright of PLoS ONE is the property of Public Library of Science and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

المؤلفون: Madhavan Nair, Rajib Kumar Dutta, Marisela Agudelo, Alison Morris, Srinivasan Chinnapaiyan, Hoshang J. Unwalla, Tiyash Parira

المصدر: PLoS ONE
PLoS ONE, Vol 12, Iss 1, p e0169161 (2017)

مصطلحات موضوعية: 0301 basic medicine, RNA viruses, Chronic bronchitis, Cell signaling, Molecular biology, lcsh:Medicine, Cystic Fibrosis Transmembrane Conductance Regulator, Gene Expression, HIV Infections, Signal transduction, Pathology and Laboratory Medicine, Biochemistry, Epithelium, 0302 clinical medicine, Immunodeficiency Viruses, Proviruses, Animal Cells, Transforming Growth Factor beta, Medicine and Health Sciences, lcsh:Science, education.field_of_study, Multidisciplinary, biology, Cell Death, Cilium, virus diseases, food and beverages, Signaling cascades, respiratory system, Cystic fibrosis transmembrane conductance regulator, 3. Good health, medicine.anatomical_structure, Medical Microbiology, Cell Processes, Mucociliary Clearance, Viral Pathogens, Viruses, Infectious diseases, RNA, Viral, tat Gene Products, Human Immunodeficiency Virus, Pathogens, Cellular Types, Anatomy, Research Article, Mucociliary clearance, Population, Viral diseases, Respiratory Mucosa, Biomolecular isolation, Biosynthesis, Microbiology, 03 medical and health sciences, Receptors, HIV, Ciliogenesis, Retroviruses, medicine, Humans, Cilia, education, Microbial Pathogens, Lung, lcsh:R, Lentivirus, Organisms, Biology and Life Sciences, HIV, Epithelial Cells, Cell Biology, Reverse Transcription, medicine.disease, DNA isolation, Immunity, Innate, respiratory tract diseases, Research and analysis methods, Pneumonia, 030104 developmental biology, Biological Tissue, Molecular biology techniques, TGF-beta signaling cascade, Immunology, biology.protein, lcsh:Q, 030217 neurology & neurosurgery

الوصف: 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.

URL الوصول: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::0a36f20438a6c2888bb8740b88fe0ca0
http://europepmc.org/articles/PMC5217953

المؤلفون: Joseph M. Rastrick, Matthew C. Catley, Meirion Davies, Christopher S. Stevenson, Megan S. Grace, Maria G. Belvisi, Toby Lawrence, Ian M. Adcock, Manolis Pasparakis, Steven Evans, Mark A. Birrell, Suffwan Eltom, Iain Kilty

المساهمون: Medical Research Council (MRC)

المصدر: PLoS ONE
PLoS ONE, Vol 8, Iss 1, p e54128 (2013)

مصطلحات موضوعية: Lipopolysaccharides, Male, Chronic bronchitis, Anatomy and Physiology, Time Factors, Pulmonology, Respiratory System, Respiratory Tract Diseases, lcsh:Medicine, Gene Expression, Pathogenesis, Mice, Pulmonary Disease, Chronic Obstructive, 0302 clinical medicine, FLOW LIMITATION, Smoke, Molecular Cell Biology, Drug Discovery, Medicine, Signaling in Cellular Processes, OXIDATIVE STRESS, lcsh:Science, Cells, Cultured, Mice, Knockout, 0303 health sciences, COPD, INDUCED EMPHYSEMA, Multidisciplinary, Kinase, Reverse Transcriptase Polymerase Chain Reaction, Smoking, NF-kappa B, EPITHELIAL-CELLS, Immunohistochemistry, Hedgehog signaling pathway, 3. Good health, I-kappa B Kinase, CHRONIC-BRONCHITIS, IKK-BETA, Science & Technology - Other Topics, MOUSE LUNG, medicine.symptom, Signal transduction, Research Article, Signal Transduction, Drugs and Devices, Drug Research and Development, General Science & Technology, Immunology, Inflammation, Thiophenes, Environmental and Occupational Lung Diseases, OBSTRUCTIVE PULMONARY-DISEASE, 03 medical and health sciences, MD Multidisciplinary, Tobacco, Animals, Humans, Biology, INDUCED LUNG INFLAMMATION, 030304 developmental biology, Science & Technology, MULTIDISCIPLINARY SCIENCES, business.industry, lcsh:R, Immunity, Transcription Factor RelA, Epithelial Cells, NFKB1, medicine.disease, Amides, respiratory tract diseases, Mice, Inbred C57BL, Disease Models, Animal, 030228 respiratory system, lcsh:Q, Transcriptional Signaling, business, BETA-DEPENDENT GENES

الوصف: Rationale COPD is an inflammatory lung disease largely associated with exposure to cigarette smoke (CS). The mechanism by which CS leads to the pathogenesis of COPD is currently unclear; it is known however that many of the inflammatory mediators present in the COPD lung can be produced via the actions of the transcription factor Nuclear Factor-kappaB (NF-κB) and its upstream signalling kinase, Inhibitor of κB kinase-2 (IKK-2). Therefore the NF-κB/IKK-2 signalling pathway may represent a therapeutic target to attenuate the inflammation associated with COPD. Aim To use a range of assays, genetically modified animals and pharmacological tools to determine the role of NF-κB in CS-induced airway inflammation. Methods NF-κB pathway activation was measured in pre-clinical models of CS-induced airway inflammation and in human lung tissue from COPD patients. This data was complemented by employing mice missing a functional NF-κB pathway in specific cell types (epithelial and myeloid cells) and with systemic inhibitors of IKK-2. Results We showed in an airway inflammation model known to be NF-κB-dependent that the NF-κB pathway activity assays and modulators were functional in the mouse lung. Then, using the same methods, we demonstrated that the NF-κB pathway appears not to play an important role in the inflammation observed after exposure to CS. Furthermore, assaying human lung tissue revealed that in the clinical samples there was also no increase in NF-κB pathway activation in the COPD lung, suggesting that our pre-clinical data is translational to human disease. Conclusions In this study we present compelling evidence that the IKK-2/NF-κB signalling pathway does not play a prominent role in the inflammatory response to CS exposure and that this pathway may not be important in COPD pathogenesis.

URL الوصول: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::7407ddefd0cab4255185ad7c0cdef4c6
http://europepmc.org/articles/PMC3551940

المؤلفون: Marije P. Hennus, Nicolaas J. G. Jansen, Frank Brus, Mark Brabander, Louis Bont, Adrianus J. van Vught

المصدر: PLoS ONE
PLoS ONE, Vol 8, Iss 12, p e83035 (2013)

مصطلحات موضوعية: Male, medicine.medical_specialty, medicine.medical_treatment, lcsh:Medicine, Respiratory Syncytial Virus Infections, Gastroenterology, Internal medicine, medicine, Intubation, Bronchiolitis, Viral, Humans, Respiratory system, lcsh:Science, Macrophage inflammatory protein, Mechanical ventilation, Inflammation, Multidisciplinary, business.industry, lcsh:R, Infant, medicine.disease, Respiration, Artificial, Respiratory Syncytial Viruses, Respiratory failure, Bronchiolitis, Immunology, Breathing, Bronchitis, Cytokines, lcsh:Q, Female, Seasons, business, Research Article

الوصف: INTRODUCTION: Respiratory insufficiency due to severe respiratory syncytial virus (RSV) infection is the most frequent cause of paediatric intensive care unit admission in infants during the winter season. Previous studies have shown increased levels of inflammatory mediators in airways of mechanically ventilated children compared to spontaneous breathing children with viral bronchiolitis. In this prospective observational multi-center study we aimed to investigate whether this increase was related to disease severity or caused by mechanical ventilation. MATERIALS AND METHODS: Nasopharyngeal aspirates were collected

URL الوصول: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::a136c792a740cc309b3d75c342421fbf
http://europepmc.org/articles/PMC3859624