WorldWideScience

Sample records for chronic lung inflammation

  1. 255 Chronic Obstructive Pulmonary Disease and Lung Cancer Share Inflammation Pathways

    OpenAIRE

    Kostas N. Syrigos; POLITI, EKATERINI; Makrilia, Nektaria; Tsimpoukis, Sotirios; Psarros, Fotis; Syrigou, Ekaterini; Dannos, Ioannis

    2012-01-01

    Background The relationship between inflammation, air obstruction and lung cancer is complex and there is still great uncertainty regarding their underlying pathophysiology. Our aim was to investigate the inflammation pathways that are implicated in both chronic obstructive pulmonary disease (COPD) and lung cancer. Methods A literature search was performed in PubMed to identify relative studies published until June 2011. Results The pathophysiology of both COPD and lung cancer includes dysreg...

  2. Lung inflammation biomarkers and lung function in children chronically exposed to arsenic

    Energy Technology Data Exchange (ETDEWEB)

    Olivas-Calderón, Edgar, E-mail: edgar_olivascalderon@hotmail.com [Department of Environmental Health, Biomedical Research Center, School of Medicine, University of Coahuila, Torreon, Coahuila (Mexico); School of Medicine, University Juarez of Durango, Gomez Palacio, Durango (Mexico); Recio-Vega, Rogelio, E-mail: rrecio@yahoo.com [Department of Environmental Health, Biomedical Research Center, School of Medicine, University of Coahuila, Torreon, Coahuila (Mexico); Gandolfi, A. Jay, E-mail: gandolfi@pharmacy.arizona.edu [Southwest Environmental Health Science Center, University of Arizona, Tucson, AZ (United States); Department of Cellular and Molecular Medicine, University of Arizona, Tucson, AZ (United States); Lantz, R. Clark, E-mail: lantz@email.arizona.edu [Department of Cellular and Molecular Medicine, University of Arizona, Tucson, AZ (United States); Department of Pharmacology and Toxicology, University of Arizona, Tucson, AZ (United States); González-Cortes, Tania, E-mail: taniagc2201@hotmail.com [Department of Environmental Health, Biomedical Research Center, School of Medicine, University of Coahuila, Torreon, Coahuila (Mexico); Gonzalez-De Alba, Cesar, E-mail: cesargonzalezalba@hotmail.com [Department of Environmental Health, Biomedical Research Center, School of Medicine, University of Coahuila, Torreon, Coahuila (Mexico); Froines, John R., E-mail: jfroines@ucla.edu [Center for Environmental and Occupational Health, School of Public Health, University of California at Los Angeles, Los Angeles, CA (United States); Espinosa-Fematt, Jorge A., E-mail: dr.jorge.espinosa@gmail.com [School of Medicine, University Juarez of Durango, Gomez Palacio, Durango (Mexico)

    2015-09-01

    Evidence suggests that exposure to arsenic in drinking water during early childhood or in utero has been associated with an increase in respiratory symptoms or diseases in the adulthood, however only a few studies have been carried out during those sensitive windows of exposure. Recently our group demonstrated that the exposure to arsenic during early childhood or in utero in children was associated with impairment in the lung function and suggested that this adverse effect could be due to a chronic inflammation response to the metalloid. Therefore, we designed this cross-sectional study in a cohort of children associating lung inflammatory biomarkers and lung function with urinary As levels. A total of 275 healthy children were partitioned into four study groups according with their arsenic urinary levels. Inflammation biomarkers were measured in sputum by ELISA and the lung function was evaluated by spirometry. Fifty eight percent of the studied children were found to have a restrictive spirometric pattern. In the two highest exposed groups, the soluble receptor for advanced glycation end products' (sRAGE) sputum level was significantly lower and matrix metalloproteinase-9 (MMP-9) concentration was higher. When the biomarkers were correlated to the urinary arsenic species, negative associations were found between dimethylarsinic (DMA), monomethylarsonic percentage (%MMA) and dimethylarsinic percentage (%DMA) with sRAGE and positive associations between %DMA with MMP-9 and with the MMP-9/tissue inhibitor of metalloproteinase (TIMP-1) ratio. In conclusion, chronic arsenic exposure of children negatively correlates with sRAGE, and positively correlated with MMP-9 and MMP-9/TIMP-1 levels, and increases the frequency of an abnormal spirometric pattern. Arsenic-induced alterations in inflammatory biomarkers may contribute to the development of restrictive lung diseases. - Highlights: • First study in children evaluating lung inflammatory biomarkers and As levels

  3. Lung inflammation biomarkers and lung function in children chronically exposed to arsenic

    International Nuclear Information System (INIS)

    Evidence suggests that exposure to arsenic in drinking water during early childhood or in utero has been associated with an increase in respiratory symptoms or diseases in the adulthood, however only a few studies have been carried out during those sensitive windows of exposure. Recently our group demonstrated that the exposure to arsenic during early childhood or in utero in children was associated with impairment in the lung function and suggested that this adverse effect could be due to a chronic inflammation response to the metalloid. Therefore, we designed this cross-sectional study in a cohort of children associating lung inflammatory biomarkers and lung function with urinary As levels. A total of 275 healthy children were partitioned into four study groups according with their arsenic urinary levels. Inflammation biomarkers were measured in sputum by ELISA and the lung function was evaluated by spirometry. Fifty eight percent of the studied children were found to have a restrictive spirometric pattern. In the two highest exposed groups, the soluble receptor for advanced glycation end products' (sRAGE) sputum level was significantly lower and matrix metalloproteinase-9 (MMP-9) concentration was higher. When the biomarkers were correlated to the urinary arsenic species, negative associations were found between dimethylarsinic (DMA), monomethylarsonic percentage (%MMA) and dimethylarsinic percentage (%DMA) with sRAGE and positive associations between %DMA with MMP-9 and with the MMP-9/tissue inhibitor of metalloproteinase (TIMP-1) ratio. In conclusion, chronic arsenic exposure of children negatively correlates with sRAGE, and positively correlated with MMP-9 and MMP-9/TIMP-1 levels, and increases the frequency of an abnormal spirometric pattern. Arsenic-induced alterations in inflammatory biomarkers may contribute to the development of restrictive lung diseases. - Highlights: • First study in children evaluating lung inflammatory biomarkers and As levels

  4. 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

  5. The role of airway macrophages in apoptotic cell clearance following acute and chronic lung inflammation.

    Science.gov (United States)

    Grabiec, Aleksander M; Hussell, Tracy

    2016-07-01

    Acute and chronic inflammatory responses in the lung are associated with the accumulation of large quantities of immune and structural cells undergoing apoptosis, which need to be engulfed by phagocytes in a process called 'efferocytosis'. Apoptotic cell recognition and removal from the lung is mediated predominantly by airway macrophages, though immature dendritic cells and non-professional phagocytes, such as epithelial cells and mesenchymal cells, can also display this function. Efficient clearance of apoptotic cells from the airways is essential for successful resolution of inflammation and the return to lung homeostasis. Disruption of this process leads to secondary necrosis of accumulating apoptotic cells, release of necrotic cell debris and subsequent uncontrolled inflammatory activation of the innate immune system by the released 'damage associated molecular patterns' (DAMPS). To control the duration of the immune response and prevent autoimmune reactions, anti-inflammatory signalling cascades are initiated in the phagocyte upon apoptotic cell uptake, mediated by a range of receptors that recognise specific phospholipids or proteins externalised on, or secreted by, the apoptotic cell. However, prolonged activation of apoptotic cell recognition receptors, such as the family of receptor tyrosine kinases Tyro3, Axl and MerTK (TAM), may delay or prevent inflammatory responses to subsequent infections. In this review, we will discuss recent advances in our understanding of the mechanism controlling apoptotic cell recognition and removal from the lung in homeostasis and during inflammation, the contribution of defective efferocytosis to chronic inflammatory lung diseases, such as chronic obstructive pulmonary disease, asthma and cystic fibrosis, and implications of the signals triggered by apoptotic cells in the susceptibility to pulmonary microbial infections. PMID:26957481

  6. Toxicogenomic analysis of susceptibility to inhaled urban particulate matter in mice with chronic lung inflammation

    Directory of Open Access Journals (Sweden)

    Yauk Carole L

    2009-03-01

    Full Text Available Abstract Background Individuals with chronic lung disease are at increased risk of adverse health effects from airborne particulate matter. Characterization of underlying pollutant-phenotype interactions may require comprehensive strategies. Here, a toxicogenomic approach was used to investigate how inflammation modifies the pulmonary response to urban particulate matter. Results Transgenic mice with constitutive pulmonary overexpression of tumour necrosis factor (TNF-α under the control of the surfactant protein C promoter and wildtype littermates (C57BL/6 background were exposed by inhalation for 4 h to particulate matter (0 or 42 mg/m3 EHC-6802 and euthanized 0 or 24 h post-exposure. The low alveolar dose of particles (16 μg did not provoke an inflammatory response in the lungs of wildtype mice, nor exacerbate the chronic inflammation in TNF animals. Real-time PCR confirmed particle-dependent increases of CYP1A1 (30–100%, endothelin-1 (20–40%, and metallothionein-II (20–40% mRNA in wildtype and TNF mice (p Conclusion Our data support the hypothesis that health effects of acute exposure to urban particles are dominated by activation of specific physiological response cascades rather than widespread changes in gene expression.

  7. Sub-chronic lung inflammation after airway exposures to Bacillus thuringiensis biopesticides in mice

    DEFF Research Database (Denmark)

    Barfod, Kenneth K; Poulsen, Steen Seier; Hammer, Maria;

    2010-01-01

    The aim of the present study was to assess possible health effects of airway exposures to Bacillus thuringiensis (Bt) based biopesticides in mice. Endpoints were lung inflammation evaluated by presence of inflammatory cells in bronchoalveolar lavage fluid (BALF), clearance of bacteria from the lung...

  8. Prostaglandins and chronic inflammation

    OpenAIRE

    Aoki, Tomohiro; Narumiya, Shuh

    2012-01-01

    Chronic inflammation is the basis of various chronic illnesses including cancer and vascular diseases. However, much has yet to be learned how inflammation becomes chronic. Prostaglandins (PGs) are well established as mediators of acute inflammation, and recent studies in experimental animals have provided evidence that they also function in transition to and maintenance of chronic inflammation. One role PGs play in such processes is amplification of cytokine signaling. As such, PGs can facil...

  9. Dissociation of lung function and airway inflammation in chronic obstructive pulmonary disease

    NARCIS (Netherlands)

    Lapperre, TS; Snoeck-Stroband, JB; Gosman, M.M.; Stolk, J; Sont, JK; Jansen, DF; Kerstjens, HAM; Postma, DS; Sterk, PJ

    2004-01-01

    Chronic obstructive pulmonary disease (COPD) is defined by progressive, irreversible airflow limitation and an inflammatory response of the lungs, usually to cigarette smoke. However, COPD is a heterogeneous disease in terms of clinical, physiologic, and pathologic presentation. We aimed to evaluate

  10. Evidence for chronic inflammation as a component of the interstitial lung disease associated with progressive systemic sclerosis

    International Nuclear Information System (INIS)

    Progressive systemic sclerosis (PSS) is a generalized disorder characterized by fibrosis of many organs including the lung parenchyma. Unlike most other interstitial disorders, traditional concepts of the interstitial lung disease associated with PSS have held it to be a ''pure'' fibrotic disorder without a significant inflammatory component. To directly evaluate whether an active alveolitis is associated with this disorder, patients with chronic interstitial lung disease and PSS were studied by open lung biopsy, gallium-67 scanning, and bronchoalveolar lavage. Histologic evaluation of the biopsies demonstrated that the interstitial fibrosis of PSS is clearly associated with the presence of macrophages, lymphocytes, and polymorphonuclear leukocytes, both in the interstitium and on the alveolar epithelial surface. Gallium-67 scans were positive in 77% of the patients, showing diffuse, primarily lower zone uptake, suggestive of active inflammation. Consistent with the histologic findings, bronchoalveolar lavage studies demonstrated a mild increase in the proportions of neutrophils and eosinophils with occasional increased numbers of lymphocytes. Importantly, alveolar macrophages from patients with PSS showed increased release of fibronectin and alveolar-macrophage-derived growth factor, mediators that together stimulate lung fibroblasts to proliferate, thus suggesting at least one mechanism modulating the lung fibrosis of these patients

  11. The Effects of Tumstatin on Vascularity, Airway Inflammation and Lung Function in an Experimental Sheep Model of Chronic Asthma.

    Science.gov (United States)

    Van der Velden, Joanne; Harkness, Louise M; Barker, Donna M; Barcham, Garry J; Ugalde, Cathryn L; Koumoundouros, Emmanuel; Bao, Heidi; Organ, Louise A; Tokanovic, Ana; Burgess, Janette K; Snibson, Kenneth J

    2016-01-01

    Tumstatin, a protein fragment of the alpha-3 chain of Collagen IV, is known to be significantly reduced in the airways of asthmatics. Further, there is evidence that suggests a link between the relatively low level of tumstatin and the induction of angiogenesis and inflammation in allergic airway disease. Here, we show that the intra-segmental administration of tumstatin can impede the development of vascular remodelling and allergic inflammatory responses that are induced in a segmental challenge model of experimental asthma in sheep. In particular, the administration of tumstatin to lung segments chronically exposed to house dust mite (HDM) resulted in a significant reduction of airway small blood vessels in the diameter range 10(+)-20 μm compared to controls. In tumstatin treated lung segments after HDM challenge, the number of eosinophils was significantly reduced in parenchymal and airway wall tissues, as well as in the bronchoalveolar lavage fluid. The expression of VEGF in airway smooth muscle was also significantly reduced in tumstatin-treated segments compared to control saline-treated segments. Allergic lung function responses were not attenuated by tumstatin administration in this model. The data are consistent with the concept that tumstatin can act to suppress vascular remodelling and inflammation in allergic airway disease. PMID:27199164

  12. Resolution of acute inflammation in the lung.

    Science.gov (United States)

    Levy, Bruce D; Serhan, Charles N

    2014-01-01

    Acute inflammation in the lung is essential to health. So too is its resolution. In response to invading microbes, noxious stimuli, or tissue injury, an acute inflammatory response is mounted to protect the host. To limit inflammation and prevent collateral injury of healthy, uninvolved tissue, the lung orchestrates the formation of specialized proresolving mediators, specifically lipoxins, resolvins, protectins, and maresins. These immunoresolvents are agonists for resolution that interact with specific receptors on leukocytes and structural cells to blunt further inflammation and promote catabasis. This process appears to be defective in several common lung diseases that are characterized by excess or chronic inflammation. Here, we review the molecular and cellular effectors of resolution of acute inflammation in the lung. PMID:24313723

  13. Effects of exercise training on atrophy gene expression in skeletal muscle of mice with chronic allergic lung inflammation

    Directory of Open Access Journals (Sweden)

    J.L.Q. Durigan

    2009-04-01

    Full Text Available We evaluated the effects of chronic allergic airway inflammation and of treadmill training (12 weeks of low and moderate intensity on muscle fiber cross-sectional area and mRNA levels of atrogin-1 and MuRF1 in the mouse tibialis anterior muscle. Six 4-month-old male BALB/c mice (28.5 ± 0.8 g per group were examined: 1 control, non-sensitized and non-trained (C; 2 ovalbumin sensitized (OA, 20 µg per mouse; 3 non-sensitized and trained at 50% maximum speed _ low intensity (PT50%; 4 non-sensitized and trained at 75% maximum speed _ moderate intensity (PT75%; 5 OA-sensitized and trained at 50% (OA+PT50%, 6 OA-sensitized and trained at 75% (OA+PT75%. There was no difference in muscle fiber cross-sectional area among groups and no difference in atrogin-1 and MuRF1 expression between C and OA groups. All exercised groups showed significantly decreased expression of atrogin-1 compared to C (1.01 ± 0.2-fold: PT50% = 0.71 ± 0.12-fold; OA+PT50% = 0.74 ± 0.03-fold; PT75% = 0.71 ± 0.09-fold; OA+PT75% = 0.74 ± 0.09-fold. Similarly significant results were obtained regarding MuRF1 gene expression compared to C (1.01 ± 0.23-fold: PT50% = 0.53 ± 0.20-fold; OA+PT50% = 0.55 ± 0.11-fold; PT75% = 0.35 ± 0.15-fold; OA+PT75% = 0.37 ± 0.08-fold. A short period of OA did not induce skeletal muscle atrophy in the mouse tibialis anterior muscle and aerobic training at low and moderate intensity negatively regulates the atrophy pathway in skeletal muscle of healthy mice or mice with allergic lung inflammation.

  14. Chronic Inflammation in Cancer Development

    OpenAIRE

    Multhoff, Gabriele; Molls, Michael; Radons, Jürgen

    2012-01-01

    Chronic inflammatory mediators exert pleiotropic effects in the development of cancer. On the one hand, inflammation favors carcinogenesis, malignant transformation, tumor growth, invasion, and metastatic spread; on the other hand inflammation can stimulate immune effector mechanisms that might limit tumor growth. The link between cancer and inflammation depends on intrinsic and extrinsic pathways. Both pathways result in the activation of transcription factors such as NF-κB, STAT-3, and HIF-...

  15. Distinct macrophage phenotypes in allergic and nonallergic lung inflammation

    NARCIS (Netherlands)

    Robbe, Patricia; Draijer, Christina; Rebelo Borg, Thiago; Luinge, Marjan; Timens, Wim; Wouters, Inge M.; Melgert, Barbro N.; Hylkema, Machteld N.

    2015-01-01

    Chronic exposure to farm environments is a risk factor for nonallergic lung disease. In contrast to allergic asthma, in which type 2 helper T cell (Th2) activation is dominant, exposure to farm dust extracts (FDE) induces Th1/Th17 lung inflammation, associated with neutrophil infiltration. Macrophag

  16. Lung inflammation caused by inhaled toxicants: a review

    OpenAIRE

    Wong, John

    2016-01-01

    John Wong, Bruce E Magun, Lisa J Wood School of Nursing, MGH Institute of Health Professions, Boston, MA, USA Abstract: Exposure of the lungs to airborne toxicants from different sources in the environment may lead to acute and chronic pulmonary or even systemic inflammation. Cigarette smoke is the leading cause of chronic obstructive pulmonary disease, although wood smoke in urban areas of underdeveloped countries is now recognized as a leading cause of respiratory disease. Mycotoxins from...

  17. Elevated circulating PAI-1 levels are related to lung function decline, systemic inflammation, and small airway obstruction in chronic obstructive pulmonary disease

    Directory of Open Access Journals (Sweden)

    Wang H

    2016-09-01

    correlation analysis showed that circulating PAI-1 was inversely correlated with pulmonary function parameters including the ratio of forced expiratory volume in 1 second to forced vital capacity (FEV1/FVC, FEV1/Pre (justified r=-0.308, P<0.001; justified r=-0.295, P=0.001, respectively and SAO indicators such as FEV3/FVC, MMEF25–75/Pre (justified r=-0.289, P=0.001; justified r=-0.273, P=0.002, respectively, but positively related to the inflammatory marker CRP (justified r=0.351, P<0.001, the small airway remolding biomarker TIMP-1, and MMP-9 (justified r=0.498, P<0.001; justified r=0.267, P=0.002, respectively. Besides, multivariable linear analysis showed that FEV1/FVC, CRP, and TIMP-1 were independent parameters associated with PAI-1. Conclusion: Our findings first illustrate that elevated serum PAI-1 levels are related to the lung function decline, systemic inflammation, and SAO in COPD, suggesting that PAI-1 may play critical roles in the pathogenesis of COPD. Keywords: plasminogen activator inhibitor-1 (PAI-1, chronic obstructive pulmonary disease (COPD, systemic inflammation, small airway obstruction (SAO

  18. Lung and vascular function during chronic severe pulmonary ischemia

    OpenAIRE

    Elizabeth M Wagner; Jenkins, John; Perino, Maria Grazia; Sukkar, Adlah; Mitzner, Wayne

    2010-01-01

    Bronchial vascular angiogenesis takes place in a variety of lung inflammatory conditions such as asthma, cystic fibrosis, lung cancer, and chronic pulmonary thromboembolic disease. However, it is unclear whether neovascularization is predominantly appropriate and preserves lung tissue or whether it contributes further to lung pathology through edema formation and inflammation. In the present study we examined airway and lung parenchymal function 14 days after left pulmonary artery ligation. I...

  19. Lung cysts in chronic paracoccidioidomycosis

    Directory of Open Access Journals (Sweden)

    Andre Nathan Costa

    2013-06-01

    Full Text Available On HRCT scans, lung cysts are characterized by rounded areas of low attenuation in the lung parenchyma and a well-defined interface with the normal adjacent lung. The most common cystic lung diseases are lymphangioleiomyomatosis, Langerhans cell histiocytosis, and lymphocytic interstitial pneumonia. In a retrospective analysis of the HRCT findings in 50 patients diagnosed with chronic paracoccidioidomycosis, we found lung cysts in 5 cases (10%, indicating that patients with paracoccidioidomycosis can present with lung cysts on HRCT scans. Therefore, paracoccidioidomycosis should be included in the differential diagnosis of cystic lung diseases.

  20. Local immunotherapy in experimental murine lung inflammation

    OpenAIRE

    sprotocols

    2015-01-01

    Authors: Caroline Uebel, Sonja Koch, Anja Maier, Nina Sopel, Anna Graser, Stephanie Mousset & Susetta Finotto ### Abstract Innovative local immunotherapy for severe lung diseases such as asthma, chronic obstructive pulmonary disease or lung cancer requires a successful delivery to access the desired cellular target in the lung. An important route is the direct instillation into the airways in contrast to delivery through the digestive tract. This protocol details a method to deliv...

  1. Mesenchymal stem cells suppress lung inflammation and airway remodeling in chronic asthma rat model via PI3K/Akt signaling pathway

    OpenAIRE

    Lin, Hai-Yan; Xu, Lei; Xie, Shuan-shuan; Yu, Fei; Hu, Hai-Yang; Song, Xiao-lian; Wang, Chang-Hui

    2015-01-01

    Background: Mesenchymal stem cells (MSCs) came out to attract wide attention and had become one of the hotspots of most diseases’ research in decades. But at present, the mechanisms of how MSCs work on chronic asthma remain undefined. Our study aims at verifying whether MSCs play a role in preventing inflammation and airway remodeling via PI3K/AKT signaling pathway in the chronic asthma rats model. Methods: First, an ovalbumin (OVA)-induced asthma model was built. MSCs were administered to ov...

  2. Chronic obstructive pulmonary disease and asthma-associated Proteobacteria, but not commensal Prevotella spp., promote Toll-like receptor 2-independent lung inflammation and pathology

    DEFF Research Database (Denmark)

    Larsen, Jeppe Madura; Musavian, Hanieh Sadat; Butt, Tariq Mahmood;

    2015-01-01

    response to three Gram-negative commensal Prevotella strains (Prevotella melaninogenica, Prevotella nanceiensis and Prevotella salivae) and three Gram-negative pathogenic Proteobacteria known to colonize lungs of patients with chronic obstructive pulmonary disease (COPD) and asthma (Haemophilus influenzae...... B, non-typeable Haemophilus influenzae and Moraxella catarrhalis). The commensal Prevotella spp. and pathogenic Proteobacteria were found to exhibit intrinsic differences in innate inflammatory capacities on murine lung cells in vitro. In vivo in mice, non-typeable H.influenzae induced severe Toll...

  3. Anemia of Inflammation and Chronic Disease

    Science.gov (United States)

    ... Disease Organizations (PDF, 270 KB). Alternate Language URL Anemia of Inflammation and Chronic Disease Page Content On ... Nutrition Points to Remember Clinical Trials What is anemia? Anemia is a condition in which a person ...

  4. Early life socioeconomic adversity is associated in adult life with chronic inflammation, carotid atherosclerosis, poorer lung function and decreased cognitive performance: a cross-sectional, population-based study

    LENUS (Irish Health Repository)

    Packard, Chris J

    2011-01-17

    Abstract Background Socioeconomic gradients in health persist despite public health campaigns and improvements in healthcare. The Psychosocial and Biological Determinants of Ill-health (pSoBid) study was designed to uncover novel biomarkers of chronic disease that may help explain pathways between socioeconomic adversity and poorer physical and mental health. Methods We examined links between indicators of early life adversity, possible intermediary phenotypes, and markers of ill health in adult subjects (n = 666) recruited from affluent and deprived areas. Classical and novel risk factors for chronic disease (lung function and atherosclerosis) and for cognitive performance were assessed, and associations sought with early life variables including conditions in the parental home, family size and leg length. Results Associations were observed between father\\'s occupation, childhood home status (owner-occupier; overcrowding) and biomarkers of chronic inflammation and endothelial activation in adults (C reactive protein, interleukin 6, intercellular adhesion molecule; P < 0.0001) but not number of siblings and leg length. Lung function (forced expiratory volume in 1 second) and cognition (Choice Reaction Time, the Stroop test, Auditory Verbal Learning Test) were likewise related to early life conditions (P < 0.001). In multivariate models inclusion of inflammatory variables reduced the impact and independence of early life conditions on lung function and measures of cognitive ability. Including variables of adult socioeconomic status attenuated the early life associations with disease biomarkers. Conclusions Adverse levels of biomarkers of ill health in adults appear to be influenced by father\\'s occupation and childhood home conditions. Chronic inflammation and endothelial activation may in part act as intermediary phenotypes in this complex relationship. Reducing the \\'health divide\\' requires that these life course determinants are taken into account.

  5. Early life socioeconomic adversity is associated in adult life with chronic inflammation, carotid atherosclerosis, poorer lung function and decreased cognitive performance: a cross-sectional, population-based study

    Directory of Open Access Journals (Sweden)

    Sattar Naveed

    2011-01-01

    Full Text Available Abstract Background Socioeconomic gradients in health persist despite public health campaigns and improvements in healthcare. The Psychosocial and Biological Determinants of Ill-health (pSoBid study was designed to uncover novel biomarkers of chronic disease that may help explain pathways between socioeconomic adversity and poorer physical and mental health. Methods We examined links between indicators of early life adversity, possible intermediary phenotypes, and markers of ill health in adult subjects (n = 666 recruited from affluent and deprived areas. Classical and novel risk factors for chronic disease (lung function and atherosclerosis and for cognitive performance were assessed, and associations sought with early life variables including conditions in the parental home, family size and leg length. Results Associations were observed between father's occupation, childhood home status (owner-occupier; overcrowding and biomarkers of chronic inflammation and endothelial activation in adults (C reactive protein, interleukin 6, intercellular adhesion molecule; P P Conclusions Adverse levels of biomarkers of ill health in adults appear to be influenced by father's occupation and childhood home conditions. Chronic inflammation and endothelial activation may in part act as intermediary phenotypes in this complex relationship. Reducing the 'health divide' requires that these life course determinants are taken into account.

  6. Radiolabelled cytokines for imaging chronic inflammation

    International Nuclear Information System (INIS)

    Diagnosis and particularly follow-up of chronic inflammatory disorders could be often difficult in clinical practice. Indeed, traditional radiological techniques reveal only structural tissue alterations and are not able to monitor functional changes occurring in tissues affected by chronic inflammation. The continuous advances in the knowledge of the pathophysiology of chronic disorders, combine with the progress of radiochemistry, led to the development of new specific radiolabelled agents for the imaging of chronic diseases. In this scenario, cytokines, due to their pivotal role in such diseases, represent good candidate as radiopharmaceuticals. (author)

  7. Anemia of Inflammation and Chronic Disease

    Science.gov (United States)

    ... 699–710. 4 Anemia of Inflammation and Chronic Disease Eating, Diet, and Nutrition People with anemia caused by ... Phone: 202–776–0544 Fax: 202–776–0545 Internet: www. hematology. org Iron Disorders Institute P.O. Box 675 Taylors, SC 29687 ...

  8. Antenatal infection/inflammation and postnatal lung maturation and injury

    Directory of Open Access Journals (Sweden)

    Ikegami Machiko

    2001-01-01

    Full Text Available Abstract Chorioamnionitis is frequently associated with preterm deliveries before 30 weeks gestation. Chorioamnionitis correlates both with an increased risk of bronchopulmonary dysplasia and with a decreased risk of respiratory distress syndrome. Both interleukin-1α and endotoxin can induce inflammation in the fetal lungs and lung maturation after preterm birth when given by intra-amniotic injection. Inflammation can also result in an arrest of alveolarization, and this lung developmental abnormality is prominent in the lungs of preterm infants that die of bronchopulmonary dysplasia. The mechanisms by which infection/inflammation can have both beneficial and injurious effects on the preterm lung remain to be characterized.

  9. Lung inflammation caused by inhaled toxicants: a review.

    Science.gov (United States)

    Wong, John; Magun, Bruce E; Wood, Lisa J

    2016-01-01

    Exposure of the lungs to airborne toxicants from different sources in the environment may lead to acute and chronic pulmonary or even systemic inflammation. Cigarette smoke is the leading cause of chronic obstructive pulmonary disease, although wood smoke in urban areas of underdeveloped countries is now recognized as a leading cause of respiratory disease. Mycotoxins from fungal spores pose an occupational risk for respiratory illness and also present a health hazard to those living in damp buildings. Microscopic airborne particulates of asbestos and silica (from building materials) and those of heavy metals (from paint) are additional sources of indoor air pollution that contributes to respiratory illness and is known to cause respiratory illness in experimental animals. Ricin in aerosolized form is a potential bioweapon that is extremely toxic yet relatively easy to produce. Although the aforementioned agents belong to different classes of toxic chemicals, their pathogenicity is similar. They induce the recruitment and activation of macrophages, activation of mitogen-activated protein kinases, inhibition of protein synthesis, and production of interleukin-1 beta. Targeting either macrophages (using nanoparticles) or the production of interleukin-1 beta (using inhibitors against protein kinases, NOD-like receptor protein-3, or P2X7) may potentially be employed to treat these types of lung inflammation without affecting the natural immune response to bacterial infections. PMID:27382275

  10. Lung inflammation caused by inhaled toxicants: a review

    Science.gov (United States)

    Wong, John; Magun, Bruce E; Wood, Lisa J

    2016-01-01

    Exposure of the lungs to airborne toxicants from different sources in the environment may lead to acute and chronic pulmonary or even systemic inflammation. Cigarette smoke is the leading cause of chronic obstructive pulmonary disease, although wood smoke in urban areas of underdeveloped countries is now recognized as a leading cause of respiratory disease. Mycotoxins from fungal spores pose an occupational risk for respiratory illness and also present a health hazard to those living in damp buildings. Microscopic airborne particulates of asbestos and silica (from building materials) and those of heavy metals (from paint) are additional sources of indoor air pollution that contributes to respiratory illness and is known to cause respiratory illness in experimental animals. Ricin in aerosolized form is a potential bioweapon that is extremely toxic yet relatively easy to produce. Although the aforementioned agents belong to different classes of toxic chemicals, their pathogenicity is similar. They induce the recruitment and activation of macrophages, activation of mitogen-activated protein kinases, inhibition of protein synthesis, and production of interleukin-1 beta. Targeting either macrophages (using nanoparticles) or the production of interleukin-1 beta (using inhibitors against protein kinases, NOD-like receptor protein-3, or P2X7) may potentially be employed to treat these types of lung inflammation without affecting the natural immune response to bacterial infections. PMID:27382275

  11. Chronic Inflammation and γδ T Cells.

    Science.gov (United States)

    Fay, Nathan S; Larson, Emily C; Jameson, Julie M

    2016-01-01

    The epithelial tissues of the skin, lungs, reproductive tract, and intestines are the largest physical barriers the body has to protect against infection. Epithelial tissues are woven with a matrix of immune cells programed to mobilize the host innate and adaptive immune responses. Included among these immune cells are gamma delta T lymphocytes (γδ T cells) that are unique in their T cell receptor usage, location, and functions in the body. Stress reception by γδ T cells as a result of traumatic epithelial injury, malignancy, and/or infection induces γδ T cell activation. Once activated, γδ T cells function to repair tissue, induce inflammation, recruit leukocytes, and lyse cells. Many of these functions are mediated via the production of cytokines and growth factors upon γδ T cell activation. Pathogenesis of many chronic inflammatory diseases involves γδ T cells; some of which are exacerbated by their presence, while others are improved. γδ T cells require a delicate balance between their need for acute inflammatory mediators to function normally and the detrimental impact imparted by chronic inflammation. This review will focus on the recent progress made in understanding how epithelial γδ T cells influence the pathogenesis of chronic inflammatory diseases and how a balance between acute and chronic inflammation impacts γδ T cell function. Future studies will be important to understand how this balance is achieved. PMID:27303404

  12. Chronic Inflammation and  T Cells

    Directory of Open Access Journals (Sweden)

    Nathan S Fay

    2016-05-01

    Full Text Available The epithelial tissues of the skin, lungs, reproductive tract, and intestines are the largest physical barriers the body has to protect against infection. Epithelial tissues are woven with a matrix of immune cells programmed to mobilize the host innate and adaptive immune responses. Included among these immune cells are  T cells that are unique in their TCR usage, location, and functions in the body. Stress reception by  T cells as a result of traumatic epithelial injury, malignancy, and/or infection induces  T cell activation. Once activated,  T cells function to repair tissue, induce inflammation, recruit leukocytes, and lyse cells. Many of these functions are mediated via the production of cytokines and growth factors upon  T cell activation. Pathogenesis of many chronic inflammatory diseases involve  T cells; some of which are exacerbated by their presence, while others are improved.  T cells require a delicate balance between their need for acute inflammatory mediators to function normally and the detrimental impact imparted by chronic inflammation. This review will focus on the recent progress made in understanding how epithelial  T cells influence the pathogenesis of chronic inflammatory diseases and how a balance between acute and chronic inflammation impacts  T cell function. Future studies will be important to understand how this balance is achieved.

  13. Eosinophilic airway inflammation: role in asthma and chronic obstructive pulmonary disease

    OpenAIRE

    George, Leena; Brightling, Christopher E.

    2016-01-01

    The chronic lung diseases, asthma and chronic obstructive pulmonary disease (COPD), are common affecting over 500 million people worldwide and causing substantial morbidity and mortality. Asthma is typically associated with Th2-mediated eosinophilic airway inflammation, in contrast to neutrophilic inflammation observed commonly in COPD. However, there is increasing evidence that the eosinophil might play an important role in 10–40% of patients with COPD. Consistently in both asthma and COPD a...

  14. Pericytes in chronic lung disease.

    Science.gov (United States)

    Rowley, Jessica E; Johnson, Jill R

    2014-01-01

    Pericytes are mesenchymal cells embedded within the abluminal surface of the endothelium of microvessels such as capillaries, pre-capillary arterioles, post-capillary and collecting venules, where they maintain microvascular homeostasis and participate in angiogenesis. In addition to their roles in supporting the vasculature and facilitating leukocyte extravasation, pericytes have been recently investigated as a subpopulation of mesenchymal stem cells (MSCs) due to their capacity to differentiate into numerous cell types including the classic MSC triad, i.e. osteocytes, chondrocytes and adipocytes. Other studies in models of fibrotic inflammatory disease of the lung have demonstrated a vital role of pericytes in myofibroblast activation, collagen deposition and microvascular remodelling, which are hallmark features of chronic lung diseases such as asthma, chronic obstructive pulmonary disorder, pulmonary fibrosis and pulmonary hypertension. Further studies into the mechanisms of the pericyte-to-myofibroblast transition and migration to fibrotic foci will hopefully clarify the role of these cells in chronic lung disease and confirm the importance of pericytes in human fibrotic pulmonary disease. PMID:25034005

  15. Inactivation of capsaicin-sensitive nerves reduces pulmonary remodeling in guinea pigs with chronic allergic pulmonary inflammation

    OpenAIRE

    C.M. Prado; G.Z. da Rocha; E.A. Leick-Maldonado; C.M. Starling; V.L. Capelozzi; M. A. Martins; I.F.L.C. Tibério

    2011-01-01

    Pulmonary remodeling is an important feature of asthma physiopathology that can contribute to irreversible changes in lung function. Although neurokinins influence lung inflammation, their exact role in the extracellular matrix (ECM) remodeling remains to be determined. Our objective was to investigate whether inactivation of capsaicin-sensitive nerves modulates pulmonary ECM remodeling in animals with chronic lung inflammation. After 14 days of capsaicin (50 mg/kg, sc) or vehicle administrat...

  16. Vaccination promotes TH1-like inflammation and survival in chronic Pseudomonas aeruginosa pneumonia. A new prophylactic principle

    DEFF Research Database (Denmark)

    Johansen, H K; Cryz, S J; Hougen, H P;

    1997-01-01

    of the macroscopic lung inflammation compared to the other vaccination groups (p = 0.009). The same effect could be obtained by IFN-gamma treatment (p = 0.004). The chronic P. aeruginosa lung infection was established in two inbred mice strains C3H/HeN, known as TH1 responders, and Balb/c, known as TH2 responders......The ongoing lung tissue damage in chronically Pseudomonas aeruginosa infected cystic fibrosis (CF) patients has been shown to be caused by elastase liberated from polymorphonuclear leukocytes (PMN), which dominate the chronic inflammation in these patients. Most CF patients, however, contract...... the chronic lung infection with P. aeruginosa after a one-year period (median) of intermittent colonization. Therefore, prevention of the onset of the chronic infection or prevention of the dominance of the inflammation by PMNs would be important goals for a vaccine strategy against P. aeruginosa in CF...

  17. Chronic Thromboembolic Pulmonary Hypertension Associated with Chronic Inflammation.

    Science.gov (United States)

    Kuse, Naoyuki; Abe, Shinji; Kuribayashi, Hidehiko; Fukuda, Asami; Kusunoki, Yuji; Narato, Ritsuko; Saito, Hitoshi; Gemma, Akihiko

    2016-01-01

    Chronic thromboembolic pulmonary hypertension (CTEPH) is one of the leading causes of severe pulmonary hypertension. According to previously reported studies in the pertinent literature, chronic inflammatory conditions may be implicated in the development of CTEPH. We herein describe the case of a 56-year-old woman who was diagnosed with CTEPH in association with chronic infection. The patient had experienced five episodes of pneumonia in the five years prior to the diagnosis of CTEPH. Blood tests from the previous five years of outpatient follow-up demonstrated that the C-reactive protein level was slightly elevated. This case suggests that a relationship exists between chronic inflammation and CTEPH, and furthermore, may contribute towards elucidating the pathophysiology of CTEPH. PMID:27250055

  18. Right Ventricular Dysfunction in Chronic Lung Disease

    OpenAIRE

    Kolb, Todd M.; Hassoun, Paul M.

    2012-01-01

    Right ventricular dysfunction arises in chronic lung disease when chronic hypoxemia and disruption of pulmonary vascular beds contribute to increase ventricular afterload, and is generally defined by hypertrophy with preserved myocardial contractility and cardiac output. Although the exact prevalence is unknown, right ventricular hypertrophy appears to be a common complication of chronic lung disease, and more frequently complicates advanced lung disease. Right ventricular failure is rare, ex...

  19. Lung Surfactant Protein D (SP-D) Response and Regulation During Acute and Chronic Lung Injury

    DEFF Research Database (Denmark)

    Gaunsbaek, Maria Quisgaard; Rasmussen, Karina Juhl; Beers, Michael F.;

    2013-01-01

    lung injury, with a sustained increment during chronic inflammation compared with acute inflammation. A quick upregulation of SP-D in serum in response to acute airway inflammation supports the notion that SP-D translocates from the airways into the vascular system, in favor of being synthesized......BACKGROUND: Surfactant protein D (SP-D) is a collection that plays important roles in modulating host defense functions and maintaining phospholipid homeostasis in the lung. The aim of current study was to characterize comparatively the SP-D response in bronchoalveolar lavage (BAL) and serum in...... three murine models of lung injury, using a validated ELISA technology for estimation of SP-D levels. METHODS: Mice were exposed to lipopolysaccharide, bleomycin, or Pneumocystis carinii (Pc) and sacrificed at different time points. RESULTS: In lipopolysaccharide-challenged mice, the level of SP-D in...

  20. PROGRESSION VARIANTS OF CHRONIC SYSTEMIC INFLAMMATION

    Directory of Open Access Journals (Sweden)

    E. Y. Gusev

    2009-01-01

    Full Text Available Abstract. Fourteen groups of patients have been investigated and divided into 2 classes. The first class included the following cohorts of patients: relatively healthy persons, age 18 to 55 yrs (n = 50; elderly persons 60 yrs old, as well as senior persons (n = 22; persons with chronic adnexitis, women in their 1st trimester of pregnancy (n = 16; climacteric syndrome (n = 16; autoimmune thyroiditis (n = 29. The second class of patients included following cohorts: elderly persons with chronic cardiac insufficiency (CCI II-III stage (n=49; valvular cardiac disease (rheumatism, n = 15; psoriatic arthritis (n = 12; reactive arthritis (n = 17; antiphospholipid syndrome, a sub-group in the 1st trimester of pregnancy (n = 5; systemic lupus erythematosus (n=49; decompensated atherosclerosis of femoral artery (n = 38; end-stage renal disease (n = 42. Plasma cytokines (TNFαα, IL-6, IL-8, IL-10, acute-phase C-reactive protein (CRP, cortisol, troponin I, myoglobin, D-dimers, interleukin-2 soluble receptor (IL-2sR, and eosinophil cationic protein (ECP were determined in all the patients, by means of immune chemiluminescent technique (Immulite; Siemens Medical Solutions Diagnostics, USA. The integral indices of systemic inflammatory reaction (SIR have been calculated, i.e., a Reactivity Coefficient (RC and a Reactivity Level (RL. In the patients belonging to Class 1 cohorts, an absence of chronic systemic inflammation features was revealed, despite of some signs of systemic inflammatory response. Meanwhile, a majority of Class 2 patients have shown the signs of chronic systemic inflammation stage I to III.

  1. The role of adipokines in chronic inflammation

    Directory of Open Access Journals (Sweden)

    Mancuso P

    2016-05-01

    Full Text Available Peter Mancuso Department of Nutritional Sciences, School of Public Health, University of Michigan, Ann Arbor, MI, USA Abstract: Adipose tissue has traditionally been defined as connective tissue that stores excess calories in the form of triacylglycerol. However, the physiologic functions attributed to adipose tissue are expanding, and it is now well established that adipose tissue is an endocrine gland. Among the endocrine factors elaborated by adipose tissue are the adipokines; hormones, similar in structure to cytokines, produced by adipose tissue in response to changes in adipocyte triacylglycerol storage and local and systemic inflammation. They inform the host regarding long-term energy storage and have a profound influence on reproductive function, blood pressure regulation, energy homeostasis, the immune response, and many other physiologic processes. The adipokines possess pro- and anti-inflammatory properties and play a critical role in integrating systemic metabolism with immune function. In calorie restriction and starvation, proinflammatory adipokines decline and anti-inflammatory adipokines increase, which informs the host of energy deficits and contributes to the suppression of immune function. In individuals with normal metabolic status, there is a balance of pro- and anti-inflammatory adipokines. This balance shifts to favor proinflammatory mediators as adipose tissue expands during the development of obesity. As a consequence, the proinflammatory status of adipose tissue contributes to a chronic low-grade state of inflammation and metabolic disorders associated with obesity. These disturbances are associated with an increased risk of metabolic disease, type 2 diabetes, cardiovascular disease, and many other pathological conditions. This review focuses on the impact of energy homeostasis on the adipokines in immune function. Keywords: calorie restriction, obesity, adipose tissue, type 2 diabetes, macrophage, infection, chronic

  2. Role of GSTM1 in Resistance for Lung Inflammation

    Science.gov (United States)

    Lung inflammation resulting from oxidant/antioxidant imbalance is a common feature of many lung diseases. In particular, the role of enzymes regulated by the NF-E2-related factor 2 (Nrf2) transcription factor has recently received increased attention. Among these antioxidant gene...

  3. Increased alveolar soluble annexin V promotes lung inflammation and fibrosis.

    Science.gov (United States)

    Buckley, Susan; Shi, Wei; Xu, Wei; Frey, Mark R; Moats, Rex; Pardo, Annie; Selman, Moises; Warburton, David

    2015-11-01

    The causes underlying the self-perpetuating nature of idiopathic pulmonary fibrosis (IPF), a progressive and usually lethal disease, remain unknown. We hypothesised that alveolar soluble annexin V contributes to lung fibrosis, based on the observation that human IPF bronchoalveolar lavage fluid (BALF) containing high annexin V levels promoted fibroblast involvement in alveolar epithelial wound healing that was reduced when annexin V was depleted from the BALF. Conditioned medium from annexin V-treated alveolar epithelial type 2 cells (AEC2), but not annexin V per se, induced proliferation of human fibroblasts and contained pro-fibrotic, IPF-associated proteins, as well as pro-inflammatory cytokines that were found to correlate tightly (r>0.95) with annexin V levels in human BALF. ErbB2 receptor tyrosine kinase in AECs was activated by annexin V, and blockade reduced the fibrotic potential of annexin V-treated AEC-conditioned medium. In vivo, aerosol delivery of annexin V to mouse lung induced inflammation, fibrosis and increased hydroxyproline, with activation of Wnt, transforming growth factor-β, mitogen-activated protein kinase and nuclear factor-κB signalling pathways, as seen in IPF. Chronically increased alveolar annexin V levels, as reflected in increased IPF BALF levels, may contribute to the progression of IPF by inducing the release of pro-fibrotic mediators. PMID:26160872

  4. The role of adipokines in chronic inflammation.

    Science.gov (United States)

    Mancuso, Peter

    2016-01-01

    Adipose tissue has traditionally been defined as connective tissue that stores excess calories in the form of triacylglycerol. However, the physiologic functions attributed to adipose tissue are expanding, and it is now well established that adipose tissue is an endocrine gland. Among the endocrine factors elaborated by adipose tissue are the adipokines; hormones, similar in structure to cytokines, produced by adipose tissue in response to changes in adipocyte triacylglycerol storage and local and systemic inflammation. They inform the host regarding long-term energy storage and have a profound influence on reproductive function, blood pressure regulation, energy homeostasis, the immune response, and many other physiologic processes. The adipokines possess pro- and anti-inflammatory properties and play a critical role in integrating systemic metabolism with immune function. In calorie restriction and starvation, proinflammatory adipokines decline and anti-inflammatory adipokines increase, which informs the host of energy deficits and contributes to the suppression of immune function. In individuals with normal metabolic status, there is a balance of pro- and anti-inflammatory adipokines. This balance shifts to favor proinflammatory mediators as adipose tissue expands during the development of obesity. As a consequence, the proinflammatory status of adipose tissue contributes to a chronic low-grade state of inflammation and metabolic disorders associated with obesity. These disturbances are associated with an increased risk of metabolic disease, type 2 diabetes, cardiovascular disease, and many other pathological conditions. This review focuses on the impact of energy homeostasis on the adipokines in immune function. PMID:27529061

  5. Chronic inflammation induces telomere dysfunction and accelerates ageing in mice

    NARCIS (Netherlands)

    Jurk, Diana; Wilson, Caroline; Passos, Joao F.; Oakley, Fiona; Correia-Melo, Clara; Greaves, Laura; Saretzki, Gabriele; Fox, Chris; Lawless, Conor; Anderson, Rhys; Hewitt, Graeme; Pender, Sylvia L. F.; Fullard, Nicola; Nelson, Glyn; Mann, Jelena; van de Sluis, Bart; Mann, Derek A.; von Zglinicki, Thomas

    2014-01-01

    Chronic inflammation is associated with normal and pathological ageing. Here we show that chronic, progressive low-grade inflammation induced by knockout of the nfkb1 subunit of the transcription factor NF-kappa B induces premature ageing in mice. We also show that these mice have reduced regenerati

  6. Systemic Inflammation in Chronic Obstructive Pulmonary Disease: May Adipose Tissue Play a Role? Review of the Literature and Future Perspectives

    OpenAIRE

    Ruzena Tkacova

    2010-01-01

    Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality worldwide. Low-grade systemic inflammation is considered a hallmark of COPD that potentially links COPD to increased rate of systemic manifestations of the disease. Obesity with/without the metabolic syndrome and cachexia represent two poles of metabolic abnormalities that may relate to systemic inflammation. On one hand systemic inflammatory syndrome likely reflects inflammation in the lungs, i.e. result...

  7. Scintigraphic studies of inflammation in diffuse lung disease

    Energy Technology Data Exchange (ETDEWEB)

    Line, B.R. (Albany Medical College, New York (USA))

    1991-09-01

    67Ga lung scintigraphy is an established means to assess alveolar inflammation in a wide variety of diffuse lung diseases. It can be used to monitor the extent and activity of the alveolitis during the course of the disease and as a follow-up evaluation to therapy. Although the mechanism of 67Ga localization is not established firmly, the isotope appears to act as a tracer for disturbed protein and cellular fluxes within the interstitium and alveolar spaces. The radiolabeled aerosol study may also be applied to the study of these fluxes as a reflection of inflammation and injury. Although Tc-DTPA clearance studies are highly sensitive to lung injury, they may be too nonspecific to separate lung injury from other physiologic processes effectively. 117 references.

  8. The molecular fingerprint of lung inflammation after blunt chest trauma

    OpenAIRE

    Ehrnthaller, Christian; Flierl, Michael; Perl, Mario; Denk, Stephanie; Unnewehr, Heike; Ward, Peter A.; Radermacher, Peter; Ignatius, Anita; Gebhard, Florian; Chinnaiyan, Arul; Huber-Lang, Markus

    2015-01-01

    Background After severe blunt chest trauma, the development of an acute lung injury (ALI) is often associated with severe or even lethal complications. Especially in multiple injured patients after blunt chest trauma ALI/ARDS [acute respiratory distress syndrome (ARDS)] is frequent. However, in the initial posttraumatic phase, inflammatory clinical signs are often not apparent and underlying changes in gene-expression profile are unknown. Methods Therefore, inflammation in lung tissue followi...

  9. Curcumin, Inflammation, and Chronic Diseases: How Are They Linked?

    Directory of Open Access Journals (Sweden)

    Yan He

    2015-05-01

    Full Text Available It is extensively verified that continued oxidative stress and oxidative damage may lead to chronic inflammation, which in turn can mediate most chronic diseases including cancer, diabetes, cardiovascular, neurological, inflammatory bowel disease and pulmonary diseases. Curcumin, a yellow coloring agent extracted from turmeric, shows strong anti-oxidative and anti-inflammatory activities when used as a remedy for the prevention and treatment of chronic diseases. How oxidative stress activates inflammatory pathways leading to the progression of chronic diseases is the focus of this review. Thus, research to date suggests that chronic inflammation, oxidative stress, and most chronic diseases are closely linked, and the antioxidant properties of curcumin can play a key role in the prevention and treatment of chronic inflammation diseases.

  10. Adult stem cells for chronic lung diseases.

    Science.gov (United States)

    Mora, Ana L; Rojas, Mauricio

    2013-10-01

    Idiopathic pulmonary fibrosis (IPF) and chronic obstructive pulmonary disease (COPD) are chronic, progressive and lethal lung diseases. The incidence of IPF and COPD increases with age, independent of exposure to common environmental risk factors. At present, there is limited understanding of the relationship between ageing and the development of chronic lung diseases. One hypothesis is that chronic injury drives to exhaustion the local and systemic repair responses in the lung. These changes are accentuated during ageing where there is a progressive accumulation of senescent cells. Recently, stem cells have emerged as a critical reparative mechanism for lung injury. In this review, we discuss the repair response of bone marrow-derived mesenchymal stem cells (B-MSC) after lung injury and how their function is affected by ageing. Our own work has demonstrated a protective role of B-MSC in several animal models of acute and chronic lung injury. We recently demonstrated the association, using animal models, between age and an increase in the susceptibility to develop severe injury and fibrosis. At the same time, we have identified functional differences between B-MSC isolated from young and old animals. Further studies are required to understand the functional impairment of ageing B-MSC, ultimately leading to a rapid stem cell depletion or fatigue, interfering with their ability to play a protective role in lung injury. The elucidation of these events will help in the development of rational and new therapeutic strategies for COPD and IPF. PMID:23648014

  11. Pleurotus eryngii Ameliorates Lipopolysaccharide-Induced Lung Inflammation in Mice

    Directory of Open Access Journals (Sweden)

    Junya Kawai

    2014-01-01

    Full Text Available Pleurotus eryngii (P. eryngii is consumed as a fresh cultivated mushroom worldwide and demonstrated to have multiple beneficial effects. We investigated the anti-inflammatory effect of P. eryngii in mice with acute lung injury (ALI. Intranasal instillation of lipopolysaccharide (LPS (10 μg/site/mouse induced marked lung inflammation (increase in the number of inflammatory cells, protein leakage, and production of nitric oxide in bronchoalveolar lavage fluid as well as histopathological damage in the lung, 6 h after treatment. Mice administered heat-treated P. eryngii (0.3–1 g/kg, p.o. (HTPE 1 h before LPS challenge showed decreased pulmonary inflammation and ameliorated histopathological damage. These results suggest that HTPE has anti-inflammatory effects against ALI. Thus, P. eryngii itself may also have anti-inflammatory effects and could be a beneficial food for the prevention of ALI induced by bacterial infection.

  12. Lung Compliance and Chronic Obstructive Pulmonary Disease

    Directory of Open Access Journals (Sweden)

    D. Papandrinopoulou

    2012-01-01

    Full Text Available Chronic obstructive pulmonary disease, namely, pulmonary emphysema and chronic bronchitis, is a chronic inflammatory response of the airways to noxious particles or gases, with resulting pathological and pathophysiological changes in the lung. The main pathophysiological aspects of the disease are airflow obstruction and hyperinflation. The mechanical properties of the respiratory system and its component parts are studied by determining the corresponding volume-pressure (P-V relationships. The consequences of the inflammatory response on the lung structure and function are depicted on the volume-pressure relationships.

  13. Preventive effects of sevoflurane treatment on lung inflammation in rats

    Institute of Scientific and Technical Information of China (English)

    Shu-Ye Song; Bing Zhou; Shuang-Mei Yang; Guo-Ze Liu; Jian-Min Tian; Xiu-Qin Yue

    2013-01-01

    Objective: To observe the effects of sevoflurane treatment on lung inflammation in rats with lipopoIysaccharide-induced acute lung injury (ALI). Methods: The rat model of ALI was established by intratracheal instillation of lipopolysaccharide (LPS). 45 infantile SD rats [body weight (272±15) g] were randomly divided into 3 groups (n=15): control group, LPS group, sevoflurane group. NS (1 mL/kg) was instillated in rats’airways of control group; LPS (5 mg/kg) was instillated in rats’airways of LPS group. Sevoflurane group rats received sevoflurane (2.4%) inhalation for a hour after LPS was instillated in rats’airways. Six hours after NS or LPS instillation, all rats were exsanguinated. Lung tissues were examined by HE staining. Expressions of TNF-α and ICAM1 mRNA were detected by semiquantitative RT-PCR techniques. The protein level of TNF-α and ICAM1 were assessed by western blot techniques. Results: In LPS group the permeability of lung tissues increased, organizational structure severely damaged and the alveolar wall tumed thick, with interstitial edema and Europhiles infiltrated increasingly. The LPS group had higher mRNA expressions of TNF-α and ICAM1 than control group and sevoflurane group (P<0.05), and LPS group had higher protein level of TNF-α and ICAM1 than control group and sevoflurane group (P<0.05). Conclusions: Sevoflurane treatment can attenuate lung inflammation in rats with lipopolysaccharide-induced acute lung injury.

  14. SOCS and inflammation in chronic renal failure

    NARCIS (Netherlands)

    Rastmanesh, M.M.

    2008-01-01

    Atherosclerosis is the major cause of morbidity and mortality in renal patients and a major health concern in western countries per se. Recent studies point to the important role of inflammation as an underlying cause of atherosclerosis. Importantly medicines that suppress inflammation lower the inc

  15. Radiopharmaceuticals for imaging chronic lymphocytic inflammation

    NARCIS (Netherlands)

    Malviya, Gaurav; De Vries, Erik F. J.; Dierckx, Rudi A.; Signore, Alberto

    2007-01-01

    In the last few decades, a number of radiopharmaceuticals for imaging inflammation have been proposed that differ in their specificity and mechanism of uptake in inflamed foci as compared to the traditional inflammation imaging agents. Radiolabelled cytokines represent a reliable tool for the precli

  16. Eosinophils in the lung – modulating apoptosis and efferocytosis in airway inflammation

    Directory of Open Access Journals (Sweden)

    Jennifer M Felton

    2014-07-01

    Full Text Available Due to the key role of the lung in efficient transfer of oxygen in exchange for carbon dioxide, a controlled inflammatory response is essential for restoration of tissue homeostasis following airway exposure to bacterial pathogens or environmental toxins. Unregulated or prolonged inflammatory responses in the lungs can lead to tissue damage, disrupting normal tissue architecture and consequently compromising efficient gaseous exchange. Failure to resolve inflammation underlies the development and/or progression of a number of inflammatory lung diseases including asthma. Eosinophils, granulocytic cells of the innate immune system, are primarily involved in defence against parasitic infections. However, the propagation of the allergic inflammatory response in chronic asthma is thought to involve excessive recruitment and impaired apoptosis of eosinophils together with defective phagocytic clearance of apoptotic cells (efferocytosis. In terms of therapeutic approaches for treatment of asthma, the widespread use of glucocorticoids is associated with a number of adverse health consequences after long-term use, while some patients suffer from steroid-resistant disease. A new approach for therapeutic intervention would be to promote the resolution of inflammation via modulation of eosinophil apoptosis and the phagocytic clearance of apoptotic cells. This review focuses on the mechanisms underpinning eosinophil-mediated lung damage, currently available treatments and therapeutic targets that might in future be harnessed to facilitate inflammation resolution by the manipulation of cell survival and clearance pathways.

  17. Eosinophils in the lung - modulating apoptosis and efferocytosis in airway inflammation.

    Science.gov (United States)

    Felton, Jennifer M; Lucas, Christopher D; Rossi, Adriano G; Dransfield, Ian

    2014-01-01

    Due to the key role of the lung in efficient transfer of oxygen in exchange for carbon dioxide, a controlled inflammatory response is essential for restoration of tissue homeostasis following airway exposure to bacterial pathogens or environmental toxins. Unregulated or prolonged inflammatory responses in the lungs can lead to tissue damage, disrupting normal tissue architecture, and consequently compromising efficient gaseous exchange. Failure to resolve inflammation underlies the development and/or progression of a number of inflammatory lung diseases including asthma. Eosinophils, granulocytic cells of the innate immune system, are primarily involved in defense against parasitic infections. However, the propagation of the allergic inflammatory response in chronic asthma is thought to involve excessive recruitment and impaired apoptosis of eosinophils together with defective phagocytic clearance of apoptotic cells (efferocytosis). In terms of therapeutic approaches for the treatment of asthma, the widespread use of glucocorticoids is associated with a number of adverse health consequences after long-term use, while some patients suffer from steroid-resistant disease. A new approach for therapeutic intervention would be to promote the resolution of inflammation via modulation of eosinophil apoptosis and the phagocytic clearance of apoptotic cells. This review focuses on the mechanisms underpinning eosinophil-mediated lung damage, currently available treatments and therapeutic targets that might in future be harnessed to facilitate inflammation resolution by the manipulation of cell survival and clearance pathways. PMID:25071763

  18. The LIM-only protein FHL2 attenuates lung inflammation during bleomycin-induced fibrosis.

    Directory of Open Access Journals (Sweden)

    Abdulaleem Alnajar

    Full Text Available Fibrogenesis is usually initiated when regenerative processes have failed and/or chronic inflammation occurs. It is characterised by the activation of tissue fibroblasts and dysregulated synthesis of extracellular matrix proteins. FHL2 (four-and-a-half LIM domain protein 2 is a scaffolding protein that interacts with numerous cellular proteins, regulating signalling cascades and gene transcription. It is involved in tissue remodelling and tumour progression. Recent data suggest that FHL2 might support fibrogenesis by maintaining the transcriptional expression of alpha smooth muscle actin and the excessive synthesis and assembly of matrix proteins in activated fibroblasts. Here, we present evidence that FHL2 does not promote bleomycin-induced lung fibrosis, but rather suppresses this process by attenuating lung inflammation. Loss of FHL2 results in increased expression of the pro-inflammatory matrix protein tenascin C and downregulation of the macrophage activating C-type lectin receptor DC-SIGN. Consequently, FHL2 knockout mice developed a severe and long-lasting lung pathology following bleomycin administration due to enhanced expression of tenascin C and impaired activation of inflammation-resolving macrophages.

  19. Th17 Responses in Chronic Allergic Airway Inflammation Abrogate Regulatory T cell-mediated Tolerance and Contribute to Airway Remodeling

    OpenAIRE

    Zhao, Jingyue; Lloyd, Clare M.; Noble, Alistair

    2012-01-01

    The role of Th17 responses in airway remodeling in asthma is currently unknown. We demonstrate that both parenteral and mucosal allergen sensitization followed by allergen inhalation leads to Th17-biased lung immune responses. Unlike Th17 cells generated in vitro, lung Th17 cells did not produce TNF-α or IL-22. Eosinophilia predominated in acute inflammation while neutrophilia and IL-17 increased in chronic disease. Allergen-induced tolerance involved Foxp3, Helios and GARP expressing regulat...

  20. Effect of the oral thrombin inhibitor dabigatran on allergic lung inflammation induced by repeated house dust mite administration in mice.

    Science.gov (United States)

    de Boer, Johannes D; Berkhout, Lea C; de Stoppelaar, Sacha F; Yang, Jack; Ottenhoff, Roelof; Meijers, Joost C M; Roelofs, Joris J T H; van't Veer, Cornelis; van der Poll, Tom

    2015-10-15

    Asthma is a chronic disease of the airways; asthma patients are hampered by recurrent symptoms of dyspnoea and wheezing caused by bronchial obstruction. Most asthma patients suffer from chronic allergic lung inflammation triggered by allergens such as house dust mite (HDM). Coagulation activation in the pulmonary compartment is currently recognized as a feature of allergic lung inflammation, and data suggest that coagulation proteases further drive inflammatory mechanisms. Here, we tested whether treatment with the oral thrombin inhibitor dabigatran attenuates allergic lung inflammation in a recently developed HDM-based murine asthma model. Mice were fed dabigatran (10 mg/g) or placebo chow during a 3-wk HDM airway exposure model. Dabigatran treatment caused systemic thrombin inhibitory activity corresponding with dabigatran levels reported in human trials. Surprisingly, dabigatran did not lead to inhibition of HDM-evoked coagulation activation in the lung as measured by levels of thrombin-antithrombin complexes and D-dimer. Repeated HDM administration caused an influx of eosinophils and neutrophils into the lungs, mucus production in the airways, and a T helper 2 response, as reflected by a rise in bronchoalveolar IL-4 and IL-5 levels and a systemic rise in IgE and HDM-IgG1. Dabigatran modestly improved HDM-induced lung pathology (P dabigatran in spite of adequate plasma levels, these results argue against clinical evaluation of dabigatran in patients with asthma.

  1. Lipopolysaccharide induced inflammation in the perivascular space in lungs

    Directory of Open Access Journals (Sweden)

    Pabst Reinhard

    2008-07-01

    Full Text Available Abstract Background Lipopolysaccharide (LPS contained in tobacco smoke and a variety of environmental and occupational dusts is a toxic agent causing lung inflammation characterized by migration of neutrophils and monocytes into alveoli. Although migration of inflammatory cells into alveoli of LPS-treated rats is well characterized, the dynamics of their accumulation in the perivascular space (PVS leading to a perivascular inflammation (PVI of pulmonary arteries is not well described. Methods Therefore, we investigated migration of neutrophils and monocytes into PVS in lungs of male Sprague-Dawley rats treated intratracheally with E. coli LPS and euthanized after 1, 6, 12, 24 and 36 hours. Control rats were treated with endotoxin-free saline. H&E stained slides were made and immunohistochemistry was performed using a monocyte marker and the chemokine Monocyte-Chemoattractant-Protein-1 (MCP-1. Computer-assisted microscopy was performed to count infiltrating cells. Results Surprisingly, the periarterial infiltration was not a constant finding in each animal although LPS-induced alveolitis was present. A clear tendency was observed that neutrophils were appearing in the PVS first within 6 hours after LPS application and were decreasing at later time points. In contrast, mononuclear cell infiltration was observed after 24 hours. In addition, MCP-1 expression was present in perivascular capillaries, arteries and the epithelium. Conclusion PVI might be a certain lung reaction pattern in the defense to infectious attacks.

  2. Improved outcome of chronic Pseudomonas aeruginosa lung infection is associated with induction of a Th1-dominated cytokine response

    DEFF Research Database (Denmark)

    Moser, C; Jensen, P O; Kobayashi, O;

    2002-01-01

    patients, the lungs of susceptible BALB/c mice were re-infected with P. aeruginosa 14 days after the initial infection. Singly-infected BALB/c mice, as well as non-infected mice, were used as controls. Decreased mortality and milder lung inflammation in re-infected BALB/c mice, as well as a tendency......Repeated challenge with antigen is involved in the pathogenesis of a variety of pulmonary diseases. Patients with cystic fibrosis (CF) experience recurrent pulmonary colonization with Pseudomonas aeruginosa before establishment of chronic lung infection. To mimic recurrent lung infections in CF...... production, in chronic P. aeruginosa lung infection in CF....

  3. TLR2-independent induction and regulation of chronic intestinal inflammation.

    Science.gov (United States)

    Boulard, Olivier; Asquith, Mark J; Powrie, Fiona; Maloy, Kevin J

    2010-02-01

    Interactions between the intestinal microflora and host innate immune receptors play a critical role in intestinal homeostasis. Several studies have shown that TLR2 can modulate inflammatory responses in the gut. TLR2 signals enhance tight junction formation and fortify the epithelial barrier, and may play a crucial role in driving acute inflammatory responses towards intestinal bacterial pathogens. In addition, TLR2 agonists can have direct effects on both Th1 cells and Treg. To define the role of TLR2 in the induction and regulation of chronic intestinal inflammation we examined the effects of TLR2 deletion on several complementary models of inflammatory bowel disease. Our results show that TLR2 signals are not required for the induction of chronic intestinal inflammation by either innate or adaptive immune responses. We further show that TLR2(-/-) mice harbor normal numbers of Foxp3(+) Treg that are able to suppress intestinal inflammation as effectively as their WT counterparts. We also did not find any intrinsic role for TLR2 for pathogenic effector T-cell responses in the gut. Thus, in contrast to their role in acute intestinal inflammation and repair, TLR2 signals may have a limited impact on the induction and regulation of chronic intestinal inflammation. PMID:19950179

  4. Genetic Deletion and Pharmacological Inhibition of PI3Kγ Reduces Neutrophilic Airway Inflammation and Lung Damage in Mice with Cystic Fibrosis-Like Lung Disease

    Directory of Open Access Journals (Sweden)

    Maria Galluzzo

    2015-01-01

    Full Text Available Purpose. Neutrophil-dominated airway inflammation is a key feature of progressive lung damage in cystic fibrosis (CF. Thus, reducing airway inflammation is a major goal to prevent lung damage in CF. However, current anti-inflammatory drugs have shown several limits. PI3Kγ plays a pivotal role in leukocyte recruitment and activation; in the present study we determined the effects of genetic deletion and pharmacologic inhibition of PI3Kγ on airway inflammation and structural lung damage in a mouse model of CF lung disease. Methods. βENaC overexpressing mice (βENaC-Tg were backcrossed with PI3Kγ-deficient (PI3KγKO mice. Tissue damage was assessed by histology and morphometry and inflammatory cell number was evaluated in bronchoalveolar lavage fluid (BALF. Furthermore, we assessed the effect of a specific PI3Kγ inhibitor (AS-605240 on inflammatory cell number in BALF. Results. Genetic deletion of PI3Kγ decreased neutrophil numbers in BALF of PI3KγKO/βENaC-Tg mice, and this was associated with reduced emphysematous changes. Treatment with the PI3Kγ inhibitor AS-605240 decreased the number of neutrophils in BALF of βENaC-Tg mice, reproducing the effect observed with genetic deletion of the enzyme. Conclusions. These results demonstrate the biological efficacy of both genetic deletion and pharmacological inhibition of PI3Kγ in reducing chronic neutrophilic inflammation in CF-like lung disease in vivo.

  5. Association between chronic obstructive pulmonary disease and lung cancer: the missing link

    Institute of Scientific and Technical Information of China (English)

    WANG Zeng-li

    2013-01-01

    Objective This review focuses on current knowledge of specific processes that drive chronic airway inflammation which are important in the pathogenesis of both chronic obstructive pulmonary disease (COPD) and lung cancer.Data sources The data used in this review were obtained mainly from studies reported in the PubMed database (1997-2012) using the terms of COPD and lung cancer.Study selection Data from published articles about prevalence of COPD-lung cancer overlap and mechanism involved in lung cancer development in COPD were identified,retrieved and reviewed.Results COPD prevalence,morbidity and mortality vary and are directly related to the prevalence of tobacco smoking except in developing countries where air pollution resulting from the burning of biomass fuels is also important.COPD is characterized by a chronic inflammation of lower airway and,importantly,the presence of COPD increases the risk of lung cancer up to 4.5 fold among long-term smokers.COPD is by far the greatest risk factor for lung cancer amongst smokers and is found in 50%-90% of patients with lung cancer.Conclusions Both COPD and lung cancer are tobacco smoking-associated chronic diseases that cluster in families and aggravate with age,and 50%-70% of patients diagnosed with lung cancer have declined spirometric evidence of COPD.Understanding and targeting common pathogenic mechanisms for lung cancer and COPD would have potential diagnostic and therapeutic implications for patients with these lung diseases and for people at risk.

  6. Inducible nitric oxide synthase inhibition attenuates physical stress-induced lung hyper-responsiveness and oxidative stress in animals with lung inflammation.

    Science.gov (United States)

    Marques, Ricardo Henrique; Reis, Fabiana G; Starling, Claudia M; Cabido, Claudia; de Almeida-Reis, Rafael; Dohlnikoff, Marisa; Prado, Carla M; Leick, Edna A; Martins, Mílton A; Tibério, Iolanda F L C

    2012-01-01

    Mechanisms involved in stress-induced asthmatic alterations have been poorly characterised. We assessed whether inducible nitric oxide synthase (iNOS) inhibition modulates the stress-amplified lung parenchyma responsiveness, oxidative stress and extracellular matrix remodelling that was previously increased by chronic lung inflammation. Guinea pigs were subjected to 7 exposures to ovalbumin (1-5 mg/ml) or saline (OVA and SAL groups) over 4 weeks. To induce behavioural stress, animals were subjected to a forced swimming protocol (5 times/week, over 2 weeks; SAL-Stress and OVA-Stress groups) 24 h after the 4th inhalation. 1400W (iNOS-specific inhibitor) was administered intraperitoneally in the last 4 days of the protocol (SAL-1400W, OVA-1400W, SAL-Stress+1400W and OVA-Stress+1400W groups). Seventy-two hours after the last inhalation, animals were anaesthetised and exsanguinated, and adrenal glands were removed. Lung tissue resistance and elastance were evaluated by oscillatory mechanics and submitted for histopathological evaluation. Stressed animals had higher adrenal weights compared to non-stressed groups, which were reduced by 1400W treatment. Behavioural stress in sensitised animals amplified the resistance and elastance responses after antigen challenge, numbers of eosinophils and iNOS+ cells, actin content and 8-iso-PGF2α density in the distal lung compared to the OVA group. 1400W treatment in ovalbumin-exposed and stressed animals reduced lung mechanics, iNOS+ cell numbers and 8-iso-PGF2α density compared to sensitised and stressed animals that received vehicle treatment. We concluded that stress amplifies the distal lung constriction, eosinophilic inflammation, iNOS expression, actin content and oxidative stress previously induced by chronic lung inflammation. iNOS-derived NO contributes to stress-augmented lung tissue functional alterations in this animal model and is at least partially due to activation of the oxidative stress pathway. PMID:22262048

  7. Iron supplementation decreases severity of allergic inflammation in murine lung.

    Directory of Open Access Journals (Sweden)

    Laura P Hale

    Full Text Available The incidence and severity of allergic asthma have increased over the last century, particularly in the United States and other developed countries. This time frame was characterized by marked environmental changes, including enhanced hygiene, decreased pathogen exposure, increased exposure to inhaled pollutants, and changes in diet. Although iron is well-known to participate in critical biologic processes such as oxygen transport, energy generation, and host defense, iron deficiency remains common in the United States and world-wide. The purpose of these studies was to determine how dietary iron supplementation affected the severity of allergic inflammation in the lungs, using a classic model of IgE-mediated allergy in mice. Results showed that mice fed an iron-supplemented diet had markedly decreased allergen-induced airway hyperreactivity, eosinophil infiltration, and production of pro-inflammatory cytokines, compared with control mice on an unsupplemented diet that generated mild iron deficiency but not anemia. In vitro, iron supplementation decreased mast cell granule content, IgE-triggered degranulation, and production of pro-inflammatory cytokines post-degranulation. Taken together, these studies show that iron supplementation can decrease the severity of allergic inflammation in the lung, potentially via multiple mechanisms that affect mast cell activity. Further studies are indicated to determine the potential of iron supplementation to modulate the clinical severity of allergic diseases in humans.

  8. Role of glutathione in immunity and inflammation in the lung

    Directory of Open Access Journals (Sweden)

    Pietro Ghezzi

    2011-01-01

    Full Text Available Pietro GhezziBrighton and Sussex Medical School, Trafford Centre, Falmer, Brighton, UKAbstract: Reactive oxygen species and thiol antioxidants, including glutathione (GSH, regulate innate immunity at various levels. This review outlines the redox-sensitive steps of the cellular mechanisms implicated in inflammation and host defense against infection, and describes how GSH is not only important as an antioxidant but also as a signaling molecule. There is an extensive literature of the role of GSH in immunity. Most reviews are biased by an oversimplified picture where “bad” free radicals cause all sorts of diseases and “good” antioxidants protect from them and prevent oxidative stress. While this may be the case in certain fields (eg, toxicology, the role of thiols (the topic of this review in immunity certainly requires wearing scientist’s goggles and being prepared to accept a more complex picture. This review aims at describing the role of GSH in the lung in the context of immunity and inflammation. The first part summarizes the history and basic concepts of this picture. The second part focuses on GSH metabolism/levels in pathology, the third on the role of GSH in innate immunity and inflammation, and the fourth gives 4 examples describing the importance of GSH in the response to infections.Keywords: antioxidants, oxidative stress, sepsis, infection, cysteine

  9. Effects of bone marrow mononuclear cells from healthy or ovalbumin-induced lung inflammation donors on recipient allergic asthma mice

    OpenAIRE

    Abreu, Soraia C.; Antunes, Mariana A.; Mendonça, Lucas; Branco, Vivian C; de Melo, Elga Bandeira; Olsen, Priscilla C.; Diaz, Bruno L.; Weiss, Daniel J; Paredes, Bruno D; Xisto, Debora G.; Morales, Marcelo M; Rocco, Patricia RM

    2014-01-01

    Introduction Asthma is characterized by a chronic inflammatory process which may lead to several changes in bone marrow cell composition. We hypothesized that bone marrow mononuclear cells (BMMCs) obtained from ovalbumin (OVA)-induced lung inflammation mice may promote different effects compared to BMMCs from healthy donors in a model of allergic asthma. Methods C57BL/6 mice were randomly assigned to two groups. In the OVA group, mice were sensitized and challenged with ovalbumin, while healt...

  10. The effect of lipopolysaccharide-induced obesity and its chronic inflammation on influenza virus-related pathology.

    Science.gov (United States)

    Ahn, Sun-Young; Sohn, Sung-Hwa; Lee, Sang-Yeon; Park, Hye-Lim; Park, Yong-Wook; Kim, Hun; Nam, Jae-Hwan

    2015-11-01

    Obese individuals show increased susceptibility to infection, low vaccine efficacy, and worse pathophysiology. However, it is unclear how obesity affects these events. The aim of this study was to investigate the effect of obesity-triggered chronic inflammation on immune cells after influenza virus infection. Control and lipopolysaccharide mice, in which an osmotic pump continually released Tween saline or lipopolysaccharide, were prepared and 3 weeks later were infected with pandemic H1N1 2009 influenza A virus. In lipopolysaccharide mice, we found a reduction in macrophage activation markers in the steady state, and reduced production of pro-inflammatory cytokines including tumor necrosis factor-α, interleukin-1β, and interleukin-6, in restimulated peritoneal macrophages. Interestingly, lipopolysaccharide-triggered chronic inflammation exacerbated the severity of pathological symptoms in the lungs after challenge with influenza virus. Taken together, the increased severity of virus-induced symptoms in obese individuals with chronic inflammation may be, at least partially, caused by macrophage dysfunction.

  11. Eosinophilic airway inflammation: role in asthma and chronic obstructive pulmonary disease.

    Science.gov (United States)

    George, Leena; Brightling, Christopher E

    2016-01-01

    The chronic lung diseases, asthma and chronic obstructive pulmonary disease (COPD), are common affecting over 500 million people worldwide and causing substantial morbidity and mortality. Asthma is typically associated with Th2-mediated eosinophilic airway inflammation, in contrast to neutrophilic inflammation observed commonly in COPD. However, there is increasing evidence that the eosinophil might play an important role in 10-40% of patients with COPD. Consistently in both asthma and COPD a sputum eosinophilia is associated with a good response to corticosteroid therapy and tailored strategies aimed to normalize sputum eosinophils reduce exacerbation frequency and severity. Advances in our understanding of the multistep paradigm of eosinophil recruitment to the airway, and the consequence of eosinophilic inflammation, has led to the development of new therapies to target these molecular pathways. In this article we discuss the mechanisms of eosinophilic trafficking, the tools to assess eosinophilic airway inflammation in asthma and COPD during stable disease and exacerbations and review current and novel anti-eosinophilic treatments. PMID:26770668

  12. Chronic Inflammation Links Cancer and Parkinson’s disease

    Directory of Open Access Journals (Sweden)

    Zhiming eLi

    2016-06-01

    Full Text Available An increasing number of genetic studies suggest that the pathogenesis of Parkinson’s disease (PD and cancer share common genes, pathways, and mechanisms. Despite a disruption in a wide range of similar biological processes, the end result is very different: uncontrolled proliferation and early neurodegeneration. Thus, the links between the molecular mechanisms that cause PD and cancer remain to be elucidated. We propose that chronic inflammation in neurons and tumors contributes to a microenvironment that favors the accumulation of DNA mutations and facilitates disease formation. This article appraises the key role of microglia, establishes the genetic role of COX2 and CARD15 in PD and cancer, and discusses prevention and treatment with this new perspective in mind. We examine the evidence that chronic inflammation is an important link between cancer and PD.

  13. Neonates with reduced neonatal lung function have systemic low-grade inflammation

    DEFF Research Database (Denmark)

    Chawes, Bo L.K.; Stokholm, Jakob; Bønnelykke, Klaus;

    2015-01-01

    Background: Children and adults with asthma and impaired lung function have been reported to have low-grade systemic inflammation, but it is unknown whether this inflammation starts before symptoms and in particular whether low-grade inflammation is present in asymptomatic neonates with reduced...... lung function. ObjectiveWe sought to investigate the possible association between neonatal lung function and biomarkers of systemic inflammation.  Methods: Plasma levels of high-sensitivity C-reactive protein (hs-CRP), IL-1β, IL-6, TNF-α, and CXCL8 (IL-8) were measured at age 6 months in 300 children...

  14. Perspectives for Monocyte/Macrophage-Based Diagnostics of Chronic Inflammation.

    Science.gov (United States)

    Kzhyshkowska, Julia; Gudima, Alexandru; Moganti, Kondaiah; Gratchev, Alexei; Orekhov, Alexander

    2016-03-01

    Low-grade chronic inflammation underlies the development of the most dangerous cardiometabolic disorders including type 2 diabetes and its vascular complications. In contrast to acute inflammation induced by bacteria and viruses, chronic inflammation can be driven by abnormal reaction to endogenous factors, including Th2 cytokines, metabolic factors like advanced glycation end products (AGEs), modified lipoproteins, or hyperglycemia. The key innate immune cells that recognize these factors in blood circulation are monocytes. Inflammatory programming of monocytes which migrate into tissues can, in turn, result into generation of tissue macrophages with pathological functions. Therefore, determination of the molecular and functional phenotype of circulating monocytes is a very promising diagnostic tool for the identification of hidden inflammation, which can precede the development of the pathology. Here we propose a new test system for the identification of inflammatory programming of monocytes: surface biomarkers and ex vivo functional system. We summarize the current knowledge about surface biomarkers for monocyte subsets, including CD16, CCR2, CX3CR1, CD64, stabilin-1 and CD36, and their association with inflammatory human disorders. Furthermore, we present the design of an ex vivo monocyte-based test system with minimal set of parameters as a potential diagnostic tool for the identification of personalized inflammatory responses. PMID:27226789

  15. Autonomic fiber sprouting in the skin in chronic inflammation

    Directory of Open Access Journals (Sweden)

    Longo Geraldine

    2008-11-01

    Full Text Available Abstract Pain is a major symptom associated with chronic inflammation. In previous work from our laboratory, we have shown that in animal models of neuropathic pain there is a sprouting of sympathetic fibers into the upper dermis, a territory normally devoid of them. However, it is not known whether such sympathetic spouting, which is likely trophic factor mediated, also occurs in chronic inflammation and arthritis. In the present study, we used a rat model of chronic inflammation in which a small single dose of complete Freund's adjuvant (CFA was injected subcutaneously, unilaterally, into the plantar surface of the hindpaw. This led to a localized long-term skin inflammation and arthritis in all joints of the hindpaw. Animals were perfused with histological fixatives at 1, 2, 3 or 4 weeks after the injection. Experimental animals treated with CFA were compared to saline-injected animals. We then investigated the changes in the pattern of peripheral innervation of the peptidergic nociceptors and sympathetic fibers in rat glabrous hindpaw skin. Antibodies directed towards calcitonin gene-related peptide (CGRP and dopamine beta-hydroxylase (DBH were used for the staining of peptidergic and sympathetic fibers, respectively. Immunofluorescence was then used to analyze the different nerve fiber populations of the upper dermis. At 4 weeks following CFA treatment, DBH-immunoreactive (IR fibers were found to sprout into the upper dermis, in a pattern similar to the one we had observed in animals with a chronic constriction injury of the sciatic nerve in a previous publication. There was also a significant increase in the density of CGRP-IR fibers in the upper dermis in CFA treated animals at 2, 3 and 4 weeks post-injection. The increased peptidergic fiber innervation and the ectopic autonomic fibers found in the upper dermis may have a role in the pain-related behavior displayed by these animals.

  16. Sub-chronic exposure to second hand smoke induces airspace leukocyte infiltration and decreases lung elastance

    Directory of Open Access Journals (Sweden)

    John M. Hartney

    2012-07-01

    Full Text Available Exposure to second hand tobacco smoke is associated with the development and/or exacerbation of several different pulmonary diseases in humans. To better understand the possible effects of second hand smoke exposure in humans, we sub-chronically (4 weeks exposed mice to a mixture of mainstream and sidestream tobacco smoke at concentrations similar to second hand smoke exposure in humans. The inflammatory response to smoke exposures was assessed at the end of this time by enumeration of pulmonary leukocyte infiltration together with measurements of lung elastance and pathology. This response was measured in both healthy wild type (C57BL/6 mice as well as mouse mutants deficient in the expression of Arhgef1 (Arhgef1–/– that display constitutive pulmonary inflammation and decreased lung elastance reminiscent of emphysema. The results from this study show that sub-chronic second hand smoke exposure leads to significantly increased numbers of airspace leukocytes in both healthy and mutant animals. While sub-chronic cigarette smoke exposure is not sufficient to induce changes in lung architecture as measured by mean linear intercept, both groups exhibit a significant decrease in lung elastance. Together these data demonstrate that even sub-chronic exposure to second hand smoke is sufficient to induce pulmonary inflammation and decrease lung elastance in both healthy and diseased animals and in the absence of tissue destruction.

  17. VBP15, a glucocorticoid analogue, is effective at reducing allergic lung inflammation in mice.

    Directory of Open Access Journals (Sweden)

    Jesse M Damsker

    Full Text Available Asthma is a chronic inflammatory condition of the lower respiratory tract associated with airway hyperreactivity and mucus obstruction in which a majority of cases are due to an allergic response to environmental allergens. Glucocorticoids such as prednisone have been standard treatment for many inflammatory diseases for the past 60 years. However, despite their effectiveness, long-term treatment is often limited by adverse side effects believed to be caused by glucocorticoid receptor-mediated gene transcription. This has led to the pursuit of compounds that retain the anti-inflammatory properties yet lack the adverse side effects associated with traditional glucocorticoids. We have developed a novel series of steroidal analogues (VBP compounds that have been previously shown to maintain anti-inflammatory properties such as NFκB-inhibition without inducing glucocorticoid receptor-mediated gene transcription. This study was undertaken to determine the effectiveness of the lead compound, VBP15, in a mouse model of allergic lung inflammation. We show that VBP15 is as effective as the traditional glucocorticoid, prednisolone, at reducing three major hallmarks of lung inflammation--NFκB activity, leukocyte degranulation, and pro-inflammatory cytokine release from human bronchial epithelial cells obtained from patients with asthma. Moreover, we found that VBP15 is capable of reducing inflammation of the lung in vivo to an extent similar to that of prednisone. We found that prednisolone--but not VBP15 shortens the tibia in mice upon a 5 week treatment regimen suggesting effective dissociation of side effects from efficacy. These findings suggest that VBP15 may represent a potent and safer alternative to traditional glucocorticoids in the treatment of asthma and other inflammatory diseases.

  18. VBP15, a glucocorticoid analogue, is effective at reducing allergic lung inflammation in mice.

    Science.gov (United States)

    Damsker, Jesse M; Dillingham, Blythe C; Rose, Mary C; Balsley, Molly A; Heier, Christopher R; Watson, Alan M; Stemmy, Erik J; Jurjus, Roslyn A; Huynh, Tony; Tatem, Kathleen; Uaesoontrachoon, Kitipong; Berry, Dana M; Benton, Angela S; Freishtat, Robert J; Hoffman, Eric P; McCall, John M; Gordish-Dressman, Heather; Constant, Stephanie L; Reeves, Erica K M; Nagaraju, Kanneboyina

    2013-01-01

    Asthma is a chronic inflammatory condition of the lower respiratory tract associated with airway hyperreactivity and mucus obstruction in which a majority of cases are due to an allergic response to environmental allergens. Glucocorticoids such as prednisone have been standard treatment for many inflammatory diseases for the past 60 years. However, despite their effectiveness, long-term treatment is often limited by adverse side effects believed to be caused by glucocorticoid receptor-mediated gene transcription. This has led to the pursuit of compounds that retain the anti-inflammatory properties yet lack the adverse side effects associated with traditional glucocorticoids. We have developed a novel series of steroidal analogues (VBP compounds) that have been previously shown to maintain anti-inflammatory properties such as NFκB-inhibition without inducing glucocorticoid receptor-mediated gene transcription. This study was undertaken to determine the effectiveness of the lead compound, VBP15, in a mouse model of allergic lung inflammation. We show that VBP15 is as effective as the traditional glucocorticoid, prednisolone, at reducing three major hallmarks of lung inflammation--NFκB activity, leukocyte degranulation, and pro-inflammatory cytokine release from human bronchial epithelial cells obtained from patients with asthma. Moreover, we found that VBP15 is capable of reducing inflammation of the lung in vivo to an extent similar to that of prednisone. We found that prednisolone--but not VBP15 shortens the tibia in mice upon a 5 week treatment regimen suggesting effective dissociation of side effects from efficacy. These findings suggest that VBP15 may represent a potent and safer alternative to traditional glucocorticoids in the treatment of asthma and other inflammatory diseases. PMID:23667681

  19. The Coordinated Action of CC Chemokines in the Lung Orchestrates Allergic Inflammation and Airway Hyperresponsiveness

    OpenAIRE

    Gonzalo, Jose-Angel; Lloyd, Clare M.; Wen, Danyi; Albar, Juan P.; Wells, Timothy N.C.; Proudfoot, Amanda; Martinez-A, C.; Dorf, Martin; Bjerke, Torbjörn; Coyle, Anthony J.; Gutierrez-Ramos, Jose-Carlos

    1998-01-01

    The complex pathophysiology of lung allergic inflammation and bronchial hyperresponsiveness (BHR) that characterize asthma is achieved by the regulated accumulation and activation of different leukocyte subsets in the lung. The development and maintenance of these processes correlate with the coordinated production of chemokines. Here, we have assessed the role that different chemokines play in lung allergic inflammation and BHR by blocking their activities in vivo. Our results show that bloc...

  20. Low Level Laser Therapy Reduces the Development of Lung Inflammation Induced by Formaldehyde Exposure

    OpenAIRE

    Cristiane Miranda da Silva; Mayara Peres Leal; Robson Alexandre Brochetti; Tárcio Braga; Luana Beatriz Vitoretti; Niels Olsen Saraiva Câmara; Amílcar Sabino Damazo; Ana Paula Ligeiro-de-Oliveira; Maria Cristina Chavantes; Adriana Lino-Dos-Santos-Franco

    2015-01-01

    Lung diseases constitute an important public health problem and its growing level of concern has led to efforts for the development of new therapies, particularly for the control of lung inflammation. Low Level Laser Therapy (LLLT) has been highlighted as a non-invasive therapy with few side effects, but its mechanisms need to be better understood and explored. Considering that pollution causes several harmful effects on human health, including lung inflammation, in this study, we have used f...

  1. Invasive Aspergillus infections in hospitalized patients with chronic lung disease

    Directory of Open Access Journals (Sweden)

    Wessolossky M

    2013-05-01

    Full Text Available Mireya Wessolossky,1 Verna L Welch,2 Ajanta Sen,1 Tara M Babu,1 David R Luke21Division of Infectious Diseases, University of Massachusetts Medical School, Worcester, MA, USA; 2Medical Affairs, Pfizer Inc, Collegeville, PA, USABackground: Although invasive pulmonary aspergillosis (IPA is more prevalent in immunocompromised patients, critical care clinicians need to be aware of the occurrence of IPA in the nontraditional host, such as a patient with chronic lung disease. The purpose of this study was to describe the IPA patient with chronic lung disease and compare the data with that of immunocompromised patients.Methods: The records of 351 patients with Aspergillus were evaluated in this single-center, retrospective study for evidence and outcomes of IPA. The outcomes of 57 patients with chronic lung disease and 56 immunocompromised patients were compared. Patients with chronic lung disease were defined by one of the following descriptive terms: emphysema, asthma, idiopathic lung disease, bronchitis, bronchiectasis, sarcoid, or pulmonary leukostasis.Results: Baseline demographics were similar between the two groups. Patients with chronic lung disease were primarily defined by emphysema (61% and asthma (18%, and immunocompromised patients primarily had malignancies (27% and bone marrow transplants (14%. A higher proportion of patients with chronic lung disease had a diagnosis of IPA by bronchoalveolar lavage versus the immunocompromised group (P < 0.03. The major risk factors for IPA were found to be steroid use in the chronic lung disease group and neutropenia and prior surgical procedures in the immunocompromised group. Overall, 53% and 69% of chronic lung disease and immunocompromised patients were cured (P = 0.14; 55% of chronic lung patients and 47% of immunocompromised patients survived one month (P = 0.75.Conclusion: Nontraditional patients with IPA, such as those with chronic lung disease, have outcomes and mortality similar to that in the

  2. Inhibition of lipopolysaccharide induced acute inflammation in lung by chlorination.

    Science.gov (United States)

    Zhang, Jinshan; Xue, Jinling; Xu, Bi; Xie, Jiani; Qiao, Juan; Lu, Yun

    2016-02-13

    Lipopolysaccharide (LPS, also called endotoxin) is a pro-inflammatory constituent of gram negative bacteria and cyanobacteria, which causes a potential health risk in the process of routine urban application of reclaimed water, such as car wash, irrigation, scenic water refilling, etc. Previous studies indicated that the common disinfection treatment, chlorination, has little effect on endotoxin activity removal measured by Limulus amebocyte lysate (LAL) assay. However, in this study, significant decrease of acute inflammatory effects was observed in mouse lung, while LAL assay still presented a moderate increase of endotoxin activity. To explore the possible mechanisms, the nuclear magnetic resonance (NMR) results showed the chlorination happened in alkyl chain of LPS molecules, which could affect the interaction between LPS and LPS-binding protein. Also the size of LPS aggregates was found to drop significantly after treatment, which could be another results of chlorination caused polarity change. In conclusion, our observation demonstrated that chlorination is effective to reduce the LPS induced inflammation in lung, and it is recommended to use health effect-based methods to assess risk removal of water treatment technologies. PMID:26530889

  3. Vaccination promotes TH1-like inflammation and survival in chronic Pseudomonas aeruginosa pneumonia in rats

    DEFF Research Database (Denmark)

    Johansen, H K; Hougen, H P; Cryz, S J;

    1995-01-01

    In a rat model of chronic Pseudomonas aeruginosa lung infection mimicking cystic fibrosis (CF) we studied whether the inflammatory response could be altered by vaccination. Rats were immunized with either a depolymerized alginate toxin A conjugate (D-ALG toxin A), purified alginate, an O......-polysaccharide toxin A conjugate, or sterile saline. After challenge none of the rats immunized with D-ALG toxin A died, in contrast to the other two vaccine groups combined (p = 0.03). A significant reduction in the severity of the macroscopic lung inflammation was seen in rats immunized with D-ALG toxin A, compared...... with the other three groups (p = 0.009). The histopathologic response in the control rats was dominated by numerous polymorphonuclear leukocytes (PMN) surrounding the alginate beads. In contrast, the histopathologic response in rats immunized with D-ALG toxin A changed within the first week after challenge from...

  4. Nontypeable Haemophilus influenzae in chronic obstructive pulmonary disease and lung cancer

    Directory of Open Access Journals (Sweden)

    Seyed Javad Moghaddam

    2011-01-01

    Full Text Available Seyed Javad Moghaddam1, Cesar E Ochoa1,2, Sanjay Sethi3, Burton F Dickey1,41Department of Pulmonary Medicine, the University of Texas MD Anderson Cancer Center, Houston, TX, USA; 2Tecnológico de Monterrey School of Medicine, Monterrey, Nuevo León, Mexico; 3Department of Medicine, University at Buffalo, State University of New York, Buffalo, NY, USA; 4Center for Inflammation and Infection, Institute of Biosciences and Technology, Texas A&M Health Science Center, Houston, TX, USAAbstract: Chronic obstructive pulmonary disease (COPD is predicted to become the third leading cause of death in the world by 2020. It is characterized by airflow limitation that is not fully reversible. The airflow limitation is usually progressive and associated with an abnormal inflammatory response of the lungs to noxious particles and gases, most commonly cigarette smoke. Among smokers with COPD, even following withdrawal of cigarette smoke, inflammation persists and lung function continues to deteriorate. One possible explanation is that bacterial colonization of smoke-damaged airways, most commonly with nontypeable Haemophilus influenzae (NTHi, perpetuates airway injury and inflammation. Furthermore, COPD has also been identified as an independent risk factor for lung cancer irrespective of concomitant cigarette smoke exposure. In this article, we review the role of NTHi in airway inflammation that may lead to COPD progression and lung cancer promotion.Keywords: COPD, NTHi, inflammation

  5. Montelukast modulates lung CysLT1 receptor expression and eosinophilic inflammation in asthmatic mice

    Institute of Scientific and Technical Information of China (English)

    Yan-jun ZHANG; Lei ZHANG; Shao-bin WANG; Hua-hao SHEN; Er-qing WEI

    2004-01-01

    AIM: To determine the expressions of cysteinyl leukotriene receptors, CysLT1 and CysLT2, in airway eosinophilic inflammation of OVA-induced asthmatic mice and the modulation by montelukast, a CysLT1 receptor antagonist.METHODS: Asthma model was induced by chronic exposure to ovalbumin (OVA) in C57BL/6 mice. The eosinophils in bronchoalveolar lavage (BAL) fluid and lung tissues were counted, IL-5 level in BAL fluid was measured,and CysLT1 and CysLT2 receptor mRNA expressions were detected by semi-quantitative RT-PCR. RESULTS:Montelukast (6 mg/kg, once per day for 20 d) significantly suppressed the increased eosinophils in BAL fluid and lung tissue, and increased IL-5 level in BAL fluid in OVA challenged mice. OVA challenge increased CysLT1 but decreased CysLT2 receptor mRNA expression. Montelukast inhibited the increased CysLT1 but not the reduced CysLT2 expression after OVA challenge. CONCLUSION: CysLT receptors are modulated immunologically, and montelukast inhibits up-regulation of CysLT1 receptor and airway eosinophilic inflammation in asthmatic mice.

  6. Continuous exposure to house dust mite elicits chronic airway inflammation and structural remodeling.

    Science.gov (United States)

    Johnson, Jill R; Wiley, Ryan E; Fattouh, Ramzi; Swirski, Filip K; Gajewska, Beata U; Coyle, Anthony J; Gutierrez-Ramos, José-Carlos; Ellis, Russ; Inman, Mark D; Jordana, Manel

    2004-02-01

    It is now fully appreciated that asthma is a disease of a chronic nature resulting from intermittent or continued aeroallergen exposure leading to airway inflammation. To investigate responses to continuous antigen exposure, mice were exposed to either house dust mite extract (HDM) or ovalbumin intranasally for five consecutive days, followed by 2 days of rest, for up to seven consecutive weeks. Continuous exposure to HDM, unlike ovalbumin, elicited severe and persistent eosinophilic airway inflammation. Flow cytometric analysis demonstrated an accumulation of CD4+ lymphocytes in the lung with elevated expression of inducible costimulator a marker of T cell activation, and of T1/ST2, a marker of helper T Type 2 effector cells. We also detected increased and sustained production of helper T cell Type 2-associated cytokines by splenocytes of HDM-exposed mice on in vitro HDM recall. Histologic analysis of the lung showed evidence of airway remodeling in mice exposed to HDM, with goblet cell hyperplasia, collagen deposition, and peribronchial accumulation of contractile tissue. In addition, HDM-exposed mice demonstrated severe airway hyperreactivity to methacholine. Finally, these responses were studied for up to 9 weeks after cessation of HDM exposure. We observed that whereas airway inflammation resolved fully, the remodeling changes did not resolve and airway hyperreactivity resolved only partly. PMID:14597485

  7. Thioredoxin-1 protects against neutrophilic inflammation and emphysema progression in a mouse model of chronic obstructive pulmonary disease exacerbation.

    Directory of Open Access Journals (Sweden)

    Naoya Tanabe

    Full Text Available BACKGROUND: Exacerbations of chronic obstructive pulmonary disease (COPD are characterized by acute enhancement of airway neutrophilic inflammation under oxidative stress and can be involved in emphysema progression. However, pharmacotherapy against the neutrophilic inflammation and emphysema progression associated with exacerbation has not been established. Thioredoxin-1 has anti-oxidative and anti-inflammatory properties and it can ameliorate neutrophilic inflammation through anti-chemotactic effects and prevent cigarette smoke (CS-induced emphysema. We aimed to determine whether thioredoxin-1 can suppress neutrophilic inflammation and emphysema progression in a mouse model of COPD exacerbation and if so, to reveal the underlying mechanisms. RESULTS: Mice were exposed to CS and then challenged with polyinosine-polycytidylic acid [poly(I:C], an agonist for virus-induced innate immunity. Airway neutrophilic inflammation, oxidative stress and lung apoptosis were enhanced in smoke-sensitive C57Bl/6, but not in smoke-resistant NZW mice. Exposure to CS and poly(I:C challenge accelerated emphysema progression in C57Bl/6 mice. Thioredoxin-1 suppressed neutrophilic inflammation and emphysema progression. Poly(I:C caused early neutrophilic inflammation through keratinocyte-derived chemokine and granulocyte-macrophage colony-stimulating factor (GM-CSF release in the lung exposed to CS. Late neutrophilic inflammation was caused by persistent GM-CSF release, which thioredoxin-1 ameliorated. Thioredoxin-1 enhanced pulmonary mRNA expression of MAP kinase phosphatase 1 (MKP-1, and the suppressive effects of thioredoxin-1 on prolonged GM-CSF release and late neutrophilic inflammation disappeared by inhibiting MKP-1. CONCLUSION: Using a mouse model of COPD exacerbation, we demonstrated that thioredoxin-1 ameliorated neutrophilic inflammation by suppressing GM-CSF release, which prevented emphysema progression. Our findings deepen understanding of the mechanisms

  8. Systemic inflammation in young adults is associated with abnormal lung function in middle age.

    Directory of Open Access Journals (Sweden)

    Ravi Kalhan

    Full Text Available BACKGROUND: Systemic inflammation is associated with reduced lung function in both healthy individuals and those with chronic obstructive pulmonary disease (COPD. Whether systemic inflammation in healthy young adults is associated with future impairment in lung health is uncertain. METHODOLOGY/PRINCIPAL FINDINGS: We evaluated the association between plasma fibrinogen and C-reactive protein (CRP in young adults and lung function in the Coronary Artery Risk Development in Young Adults cohort study. Higher year 7 fibrinogen was associated with greater loss of forced vital capacity (FVC between years 5 and 20 (439 mL in quartile 4 vs. 398 mL in quartile 1, P<0.001 and forced expiratory volume in 1 second (FEV(1 (487 mL in quartile 4 vs. 446 mL in quartile 1, P<0.001 independent of cigarette smoking, body habitus, baseline lung function and demographic factors. Higher year 7 CRP was also associated with both greater loss of FVC (455 mL in quartile 4 vs. 390 mL in quartile 1, P<0.001 and FEV(1 (491 mL in quartile 4 vs. 442 mL in quartile 1, P = 0.001. Higher year 7 fibrinogen and CRP were associated with abnormal FVC at year 20 (odds ratio (OR per standard deviation 1.51 (95% confidence interval (CI: 1.30-1.75 for fibrinogen and 1.35 (95% CI: 1.14-1.59 for CRP. Higher year 5 fibrinogen was additionally associated with abnormal FEV(1. A positive interaction was observed between pack-years cigarette smoking and year 7 CRP for the COPD endpoint, and among participants with greater than 10 pack-years of cigarette exposure, year 7 CRP was associated with greater odds of COPD at year 20 (OR per standard deviation 1.53 (95% CI: 1.08-2.16. CONCLUSION/SIGNIFICANCE: Systemic inflammation in young adults is associated with abnormal lung function in middle age. In particular, elevated CRP may identify vulnerability to COPD among individuals who smoke. TRIAL REGISTRATION: ClinicalTrials.gov NCT00005130.

  9. Anti-inflammatory effects of naringin in chronic pulmonary neutrophilic inflammation in cigarette smoke-exposed rats

    OpenAIRE

    Nie, YC; Wu, H.; Li, PB; Luo, YL; Long, K.; Xie, LM; Shen, JG; Su, WW

    2012-01-01

    Naringin, a well-known flavanone glycoside of grapefruit and citrus fruits, was found to be as an effective anti-inflammatory compound in our previous lipopolysaccharide-induced acute lung injury mouse model via blockading activity of nuclear factor κB. The current study sought to explore the anti-inflammatory effects of naringin on chronic pulmonary neutrophilic inflammation in cigarette smoke (CS)-induced rats. Seventy Sprague-Dawley rats were randomly divided into seven groups to study the...

  10. A PAF receptor antagonist inhibits acute airway inflammation and late-phase responses but not chronic airway inflammation and hyperresponsiveness in a primate model of asthma

    Directory of Open Access Journals (Sweden)

    R. H. Gundel

    1992-01-01

    Full Text Available We have examined the effects of a PAF receptor antagonist, WEB 2170, on several indices of acute and chronic airway inflammation and associated changes in lung function in a primate model of allergic asthma. A single oral administration WEB 2170 provided dose related inhibition of the release of leukotriene C4 (LTC4 and prostaglandin D2 (PGD2 recovered and quantified in bronchoalveolar lavage (BAL fluid obtained during the acute phase response to inhaled antigen. In addition, oral WEB 2170 treatment in dual responder primates blocked the acute influx of neutrophils into the airways as well as the associated late-phase airway obstruction occurring 6 h after antigen inhalation. In contrast, a multiple dosing regime with WEB 2170 (once a day for 7 consecutive days failed to reduce the chronic airway inflammation (eosinophilic and associated airway hyperresponsiveness to inhaled methacholine that is characteristic of dual responder monkeys. Thus, we conclude that the generation of PAF following antigen inhalation contributes to the development of lipid mediators, acute airway inflammation and associated late-phase airway obstruction in dual responder primates; however, PAF does not play a significant role in the maintenance of chronic airway inflammation and associated airway hyperresponsiveness in this primate model.

  11. Investigation of airway inflammation and asthma by repeated bronchoalveolar lavage combined with measurements of airway and lung tissue mechanics in individual rats.

    OpenAIRE

    dr Bánfi Andrea

    2011-01-01

    Acute and chronic airway inflammations are the main pathogenetic features of numerous pulmonary diseases. There are several methods studying the pathomechanisms of inflammatory respiratory diseases. To asses the severity of lung diseases, the bronchoalveolar lavage (BAL) and lung function tests are the most current diagnostic methods in the experimental and human pulmonology. However, repetition of BAL procedures and assessments of respiratory mechanic parameters in small rodents (mice and ra...

  12. Cardiovascular Disease and Chronic Inflammation in End Stage Kidney Disease

    Directory of Open Access Journals (Sweden)

    Sofia Zyga

    2013-01-01

    Full Text Available Background: Chronic Kidney Disease (CKD is one of the most severe diseases worldwide. In patients affected by CKD, a progressive destruction of the nephrons is observed not only in structuralbut also in functional level. Atherosclerosis is a progressive disease of large and medium-sized arteries. It is characterized by the deposition of lipids and fibrous elements and is a common complication of the uremic syndrome because of the coexistence of a wide range of risk factors. High blood pressure, anaemia, insulin resistance, inflammation, high oxidative stress are some of the most common factors that cause cardiovascular disease and atherogenesis in patients suffering from End Stage Kidney Disease (ESRD. At the same time, the inflammatory process constitutes a common element in the apparition and development of CKD. A wide range of possible causes can justify the development of inflammation under uremic conditions. Such causes are oxidative stress, oxidation, coexistentpathological conditions as well as factors that are due to renal clearance techniques. Patients in ESRD and coronary disease usually show increased acute phase products. Pre-inflammatory cytokines, such as IL-6 and TNF-a, and acute phase reactants, such as CRP and fibrinogen, are closely related. The treatment of chronic inflammation in CKD is of high importance for the development ofthe disease as well as for the treatment of cardiovascular morbidity.Conclusions: The treatment factors focus on the use of renin-angiotensic system inhibitors, acetylsalicylic acid, statins and anti-oxidant treatment in order to prevent the action of inflammatorycytokines that have the ability to activate the mechanisms of inflammation.

  13. Ginseng treatment reduces bacterial load and lung pathology in chronic Pseudomonas aeruginosa pneumonia in rats

    DEFF Research Database (Denmark)

    Song, Z; Johansen, H K; Faber, V;

    1997-01-01

    the inflammation and antibody responses could be changed by treatment with the Chinese herbal medicine ginseng. An aqueous extract of ginseng was injected subcutaneously, and cortisone and saline were used as controls. Two weeks after challenge with P. aeruginosa, the ginseng-treated group showed a significantly...... against P. aeruginosa sonicate and a shift from an acute type to a chronic type of lung inflammation compared to those in the control and cortisone-treated groups were observed. These findings indicate that ginseng treatment of an experimental P. aeruginosa pneumonia in rats promotes a cellular response...... resembling a TH1-like response. On the basis of these results it is suggested that ginseng may have the potential to be a promising natural medicine, in conjunction with other forms of treatment, for CF patients with chronic P. aeruginosa lung infection....

  14. Bone Marrow Stromal Cells Attenuate Lung Injury in a Murine Model of Neonatal Chronic Lung Disease

    OpenAIRE

    Aslam, Muhammad; Baveja, Rajiv; Liang, Olin D.; Fernandez-Gonzalez, Angeles; Lee, Changjin; Mitsialis, S. Alex; Kourembanas, Stella

    2009-01-01

    Rationale: Neonatal chronic lung disease, known as bronchopulmonary dysplasia (BPD), remains a serious complication of prematurity despite advances in the treatment of extremely low birth weight infants.

  15. Acute lung injury: How macrophages orchestrate resolution of inflammation and tissue repair

    Directory of Open Access Journals (Sweden)

    Susanne eHerold

    2011-11-01

    Full Text Available Lung macrophages are long living cells with broad differentiation potential, which reside in the lung interstitium and alveoli or are organ-recruited upon inflammatory stimuli. A role of resident and recruited macrophages in initiating and maintaining pulmonary inflammation in lung infection or injury has been convincingly demonstrated. More recent reports suggest that lung macrophages are main orchestrators of termination and resolution of inflammation and initiators of parenchymal repair processes that are essential for return to homeostasis with normal gas exchange. In this review we will discuss cellular cross-talk mechanisms and molecular pathways of macrophage plasticity which define their role in inflammation resolution and in initiation of lung barrier repair following lung injury.

  16. Longitudinal study of a mouse model of chronic pulmonary inflammation using breath hold gated micro-CT

    International Nuclear Information System (INIS)

    To evaluate the feasibility of using automatic quantitative analysis of breath hold gated micro-CT images to detect and monitor disease in a mouse model of chronic pulmonary inflammation, and to compare image-based measurements with pulmonary function tests and histomorphometry. Forty-nine A/J mice were used, divided into control and inflammation groups. Chronic inflammation was induced by silica aspiration. Fourteen animals were imaged at baseline, and 4, 14, and 34 weeks after silica aspiration, using micro-CT synchronized with ventilator-induced breath holds. Lung input impedance was measured as well using forced oscillation techniques. Five additional animals from each group were killed after micro-CT for comparison with histomorphometry. At all time points, micro-CT measurements show statistically significant differences between the two groups, while first differences in functional test parameters appear at 14 weeks. Micro-CT measurements correlate well with histomorphometry and discriminate diseased and healthy groups better than functional tests. Longitudinal studies using breath hold gated micro-CT are feasible on the silica-induced model of chronic pulmonary inflammation, and automatic measurements from micro-CT images correlate well with histomorphometry, being more sensitive than functional tests to detect lung damage in this model. (orig.)

  17. Longitudinal study of a mouse model of chronic pulmonary inflammation using breath hold gated micro-CT

    Energy Technology Data Exchange (ETDEWEB)

    Artaechevarria, Xabier; Perez-Martin, Daniel; Munoz-Barrutia, Arrate; Ortiz-de-Solorzano, Carlos [Center for Applied Medical Research, University of Navarra, Cancer Imaging Laboratory, Oncology Division, Pamplona (Spain); Blanco, David; Biurrun, Gabriel de; Montuenga, Luis M. [Center for Applied Medical Research, University of Navarra, Biomarkers Laboratory, Pamplona (Spain); Torres, Juan P. de; Zulueta, Javier J. [Clinica Universidad de Navarra, Pneumology Department, Pamplona (Spain); Bastarrika, Gorka [Clinica Universidad de Navarra, Radiology Department, Pamplona (Spain)

    2010-11-15

    To evaluate the feasibility of using automatic quantitative analysis of breath hold gated micro-CT images to detect and monitor disease in a mouse model of chronic pulmonary inflammation, and to compare image-based measurements with pulmonary function tests and histomorphometry. Forty-nine A/J mice were used, divided into control and inflammation groups. Chronic inflammation was induced by silica aspiration. Fourteen animals were imaged at baseline, and 4, 14, and 34 weeks after silica aspiration, using micro-CT synchronized with ventilator-induced breath holds. Lung input impedance was measured as well using forced oscillation techniques. Five additional animals from each group were killed after micro-CT for comparison with histomorphometry. At all time points, micro-CT measurements show statistically significant differences between the two groups, while first differences in functional test parameters appear at 14 weeks. Micro-CT measurements correlate well with histomorphometry and discriminate diseased and healthy groups better than functional tests. Longitudinal studies using breath hold gated micro-CT are feasible on the silica-induced model of chronic pulmonary inflammation, and automatic measurements from micro-CT images correlate well with histomorphometry, being more sensitive than functional tests to detect lung damage in this model. (orig.)

  18. HE3286, an oral synthetic steroid, treats lung inflammation in mice without immune suppression

    Directory of Open Access Journals (Sweden)

    Frincke James M

    2010-10-01

    Full Text Available Abstract Background 17α-Ethynyl-5-androsten-3β, 7β, 17β-triol (HE3286 is a synthetic derivative of an endogenous steroid androstenetriol (β-AET, a metabolite of the abundant adrenal steroid deyhdroepiandrosterone (DHEA, with broad anti-inflammatory activities. We tested the ability of this novel synthetic steroid with improved pharmacological properties to limit non-productive lung inflammation in rodents and attempted to gauge its immunological impact. Methods and Results In mice, oral treatment with HE3286 (40 mg/kg significantly (p in vivo (ovalbumin immunization. When mice treated for two weeks with HE3286 were challenged with K. pneumoniae, nearly identical survival kinetics were observed in vehicle-treated, HE3286-treated and untreated groups. Conclusions HE3286 represents a novel, first-in-class anti-inflammatory agent that may translate certain benefits of β-AET observed in rodents into treatments for chronic inflammatory pulmonary disease.

  19. Effects of inflammation and fibrosis on pulmonary function in diffuse lung fibrosis.

    OpenAIRE

    Chinet, T; Jaubert, F; Dusser, D.; Danel, C.; Chrétien, J.; Huchon, G J

    1990-01-01

    To investigate the relation between lung function and inflammation and fibrosis in patients with diffuse lung fibrosis, a study was made of untreated patients without appreciable airway obstruction (14 patients with cryptogenic fibrosing alveolitis and seven with pneumoconiosis). Quantitative assessment of inflammatory infiltration and fibrosis was carried out on open lung biopsy specimens and compared with lung volumes, carbon monoxide transfer factor (TLCO), TLCO corrected for alveolar volu...

  20. MUC18 Regulates Lung Rhinovirus Infection and Inflammation

    Science.gov (United States)

    Berman, Reena; Jiang, Di; Wu, Qun; Stevenson, Connor R.; Schaefer, Niccolette R.; Chu, Hong Wei

    2016-01-01

    Background MUC18 is upregulated in the lungs of asthma and COPD patients. It has been shown to have pro-inflammatory functions in cultured human airway epithelial cells during viral infections and in mice during lung bacterial infections. However, the in vivo role of MUC18 in the context of viral infections remains poorly understood. The goal of this study is to define the in vivo function of MUC18 during respiratory rhinovirus infection. Methods Muc18 wild-type (WT) and knockout (KO) mice were infected with human rhinovirus 1B (HRV-1B) and sacrificed after 1 day to determine the inflammatory and antiviral responses. To examine the direct effects of Muc18 on viral infection, tracheal epithelial cells isolated from WT and KO mice were grown under air-liquid interface and infected with HRV-1B. Finally, siRNA mediated knockdown of MUC18 was performed in human airway epithelial cells (AECs) to define the impact of MUC18 on human airway response to HRV-1B. Results Both viral load and neutrophilic inflammation were significantly decreased in Muc18 KO mice compared to WT mice. In the in vitro setting, viral load was significantly lower and antiviral gene expression was higher in airway epithelial cells of Muc18 KO mice than the WT mice. Furthermore, in MUC18 knockdown human AECs, viral load was decreased and antiviral gene expression was increased compared to controls. Conclusions Our study is the first to demonstrate MUC18’s pro-inflammatory and pro-viral function in an in vivo mouse model of rhinovirus infection. PMID:27701461

  1. Chronic Lymphocytic Inflammation Specifies the Organ Tropism of Prions

    Science.gov (United States)

    Heikenwalder, Mathias; Zeller, Nicolas; Seeger, Harald; Prinz, Marco; Klöhn, Peter-Christian; Schwarz, Petra; Ruddle, Nancy H.; Weissmann, Charles; Aguzzi, Adriano

    2005-02-01

    Prions typically accumulate in nervous and lymphoid tissues. Because proinflammatory cytokines and immune cells are required for lymphoid prion replication, we tested whether inflammatory conditions affect prion pathogenesis. We administered prions to mice with five inflammatory diseases of the kidney, pancreas, or liver. In all cases, chronic lymphocytic inflammation enabled prion accumulation in otherwise prion-free organs. Inflammatory foci consistently correlated with lymphotoxin up-regulation and ectopic induction of FDC-M1+ cells expressing the normal cellular prion protein PrPC. By contrast, inflamed organs of mice lacking lymphotoxin-α or its receptor did not accumulate the abnormal isoform PrPSc, nor did they display infectivity upon prion inoculation. By expanding the tissue distribution of prions, chronic inflammatory conditions may act as modifiers of natural and iatrogenic prion transmission.

  2. Effect of short-term stainless steel welding fume inhalation exposure on lung inflammation, injury, and defense responses in rats

    International Nuclear Information System (INIS)

    had a delayed effect on pulmonary inflammation. Additional chronic inhalation studies are needed to further examine the lung effects associated with SS welding fume exposure

  3. Melatonin decreases the expression of inflammation and apoptosis markers in the lung of a senescence-accelerated mice model.

    Science.gov (United States)

    Puig, Ángela; Rancan, Lisa; Paredes, Sergio D; Carrasco, Adrián; Escames, Germaine; Vara, Elena; Tresguerres, Jesús A F

    2016-03-01

    Aging is associated with an increase in oxidative stress and inflammation. The aging lung is particularly affected since it is continuously exposed to environmental oxidants while antioxidant machinery weakens with age. Melatonin, a free radical scavenger, counteracts inflammation and apoptosis in healthy cells from several tissues. Its effects on the aging lung are, however, not yet fully understood. This study aimed to investigate the effect of chronic administration of melatonin on the expression of inflammation markers (TNF-α, IL-1β, NFκB2, HO-1) and apoptosis parameters (BAD, BAX, AIF) in the lung tissue of male senescence-accelerated prone mice (SAMP8). In addition, RNA oxidative damage, as the formation of 8-hydroxyguanosine (8-OHG), was also evaluated. Young and old animals, aged 2 and 10 months respectively, were divided into 4 groups: untreated young, untreated old, old mice treated with 1mg/kg/day melatonin, and old animals treated with 10mg/kg/day melatonin. Untreated young and old male senescence accelerated resistant mice (SAMR1) were used as controls. After 30 days of treatment, animals were sacrificed. Lungs were collected and immediately frozen in liquid nitrogen. mRNA and protein expressions were measured by RT-PCR and Western blotting, respectively. Levels of 8-OHG were quantified by ELISA. Mean values were analyzed using ANOVA. Old nontreated SAMP8 animals showed increased (paging-derived inflammation (paging, the effect being counteracted with melatonin (pAging also caused a significant elevation (panimals treated with melatonin (paging lungs, exerting a protective effect on age-induced damage. PMID:26656745

  4. Ncf1 polymorphism reveals oxidative regulation of autoimmune chronic inflammation.

    Science.gov (United States)

    Holmdahl, Rikard; Sareila, Outi; Olsson, Lina M; Bäckdahl, Liselotte; Wing, Kajsa

    2016-01-01

    The current review on the function of neutrophil cytosolic factor 1 (NCF1) and induced reactive oxygen species (ROS) is based on a genetic search for the major genes controlling autoimmune inflammatory disorders. Surprisingly, the disease-promoting allele determined a lower ROS response and was therefore in complete contrast to the prevailing dogma. Once cloned, it opened the possibility to dissect this complex field from a new angle and with the possibilities to study the role of ROS in vivo. We found that NCF1 and NADPH oxidase 2 (NOX2) complex-derived ROS is an important regulator of several chronic inflammatory disorders by using models for rheumatoid arthritis, multiple sclerosis, psoriasis and psoriasis arthritis, gout, and lupus. ROS could therefore affect many different types of diseases and the common denominator seems to be that ROS regulate macrophages, which prevents inflammation from going chronic. The role of ROS is currently changing from being seen as toxic agents that will promote inflammation toward a more complex view with ROS as crucial regulators of immune and inflammatory pathways. PMID:26683156

  5. Important role of platelets in modulating endotoxin-induced lung inflammation in CFTR-deficient mice.

    Directory of Open Access Journals (Sweden)

    Caiqi Zhao

    Full Text Available Mutation of CFTR (cystic fibrosis transmembrane conductance regulator leads to cystic fibrosis (CF. Patients with CF develop abnormalities of blood platelets and recurrent lung inflammation. However, whether CFTR-mutated platelets play a role in the development of lung inflammation is elusive. Therefore, we intratracheally challenged wildtype and F508del (a common type of CFTR mutation mice with LPS to observe changes of F508del platelets in the peripheral blood and indexes of lung inflammation (BAL neutrophils and protein levels. Furthermore, we investigated whether or not and how F508del platelets modulate the LPS-induced acute lung inflammation by targeting anti-platelet aggregation, depletion of neutrophils, reconstitution of bone marrow or neutrophils, blockade of P-selectin glycoprotein ligand-1 (PSGL-1, platelet activating factor (PAF, and correction of mutated CFTR trafficking. We found that LPS-challenged F508del mice developed severe thrombocytopenia and had higher levels of plasma TXB2 coincided with neutrophilic lung inflammation relative to wildtype control. Inhibition of F508del platelet aggregation or depletion of F508del neutrophils diminished the LPS-induced lung inflammation in the F508del mice. Moreover, wildtype mice reconstituted with either F508del bone marrow or neutrophils developed worse thrombocytopenia. Blocking PSGL-1, platelet activating factor (PAF, or rectifying trafficking of mutated CFTR in F508del mice diminished and alveolar neutrophil transmigration in the LPS-challenged F508del mice. These findings suggest that F508del platelets and their interaction with neutrophils are requisite for the development of LPS-induced lung inflammation and injury. As such, targeting platelets might be an emerging strategy for dampening recurrent lung inflammation in cystic fibrosis patients.

  6. Proteases and antiproteases in chronic neutrophilic lung disease - relevance to drug discovery.

    LENUS (Irish Health Repository)

    Greene, Catherine M

    2009-10-01

    Chronic inflammatory lung diseases such as cystic fibrosis and emphysema are characterized by higher-than-normal levels of pulmonary proteases. While these enzymes play important roles such as bacterial killing, their dysregulated expression or activity can adversely impact on the inflammatory process. The existence of efficient endogenous control mechanisms that can dampen or halt this overexuberant protease activity in vivo is essential for the effective resolution of inflammatory lung disease. The function of pulmonary antiproteases is to fulfil this role. Interestingly, in addition to their antiprotease activity, protease inhibitors in the lung also often possess other intrinsic properties that contribute to microbial killing or termination of the inflammatory process. This review will outline important features of chronic inflammation that are regulated by pulmonary proteases and will describe the various mechanisms by which antiproteases attempt to counterbalance exaggerated protease-mediated inflammatory events. These proteases, antiproteases and their modifiers represent interesting targets for therapeutic intervention.

  7. Autophagy deficiency in macrophages enhances NLRP3 inflammasome activity and chronic lung disease following silica exposure.

    Science.gov (United States)

    Jessop, Forrest; Hamilton, Raymond F; Rhoderick, Joseph F; Shaw, Pamela K; Holian, Andrij

    2016-10-15

    Autophagy is an important metabolic mechanism that can promote cellular survival following injury. The specific contribution of autophagy to silica-induced inflammation and disease is not known. The objective of these studies was to determine the effects of silica exposure on the autophagic pathway in macrophages, as well as the general contribution of autophagy in macrophages to inflammation and disease. Silica exposure enhanced autophagic activity in vitro in Bone Marrow derived Macrophages and in vivo in Alveolar Macrophages isolated from silica-exposed mice. Impairment of autophagy in myeloid cells in vivo using Atg5(fl/fl)LysM-Cre(+) mice resulted in enhanced cytotoxicity and inflammation after silica exposure compared to littermate controls, including elevated IL-18 and the alarmin HMGB1 in the whole lavage fluid. Autophagy deficiency caused some spontaneous inflammation and disease. Greater silica-induced acute inflammation in Atg5(fl/fl)LysM-Cre(+) mice correlated with increased fibrosis and chronic lung disease. These studies demonstrate a critical role for autophagy in suppressing silica-induced cytotoxicity and inflammation in disease development. Furthermore, this data highlights the importance of basal autophagy in macrophages and other myeloid cells in maintaining lung homeostasis.

  8. Low Level Laser Therapy Reduces the Development of Lung Inflammation Induced by Formaldehyde Exposure.

    Directory of Open Access Journals (Sweden)

    Cristiane Miranda da Silva

    Full Text Available Lung diseases constitute an important public health problem and its growing level of concern has led to efforts for the development of new therapies, particularly for the control of lung inflammation. Low Level Laser Therapy (LLLT has been highlighted as a non-invasive therapy with few side effects, but its mechanisms need to be better understood and explored. Considering that pollution causes several harmful effects on human health, including lung inflammation, in this study, we have used formaldehyde (FA, an environmental and occupational pollutant, for the induction of neutrophilic lung inflammation. Our objective was to investigate the local and systemic effects of LLLT after FA exposure. Male Wistar rats were exposed to FA (1% or vehicle (distillated water during 3 consecutive days and treated or not with LLLT (1 and 5 hours after each FA exposure. Non-manipulated rats were used as control. 24 h after the last FA exposure, we analyzed the local and systemic effects of LLLT. The treatment with LLLT reduced the development of neutrophilic lung inflammation induced by FA, as observed by the reduced number of leukocytes, mast cells degranulated, and a decreased myeloperoxidase activity in the lung. Moreover, LLLT also reduced the microvascular lung permeability in the parenchyma and the intrapulmonary bronchi. Alterations on the profile of inflammatory cytokines were evidenced by the reduced levels of IL-6 and TNF-α and the elevated levels of IL-10 in the lung. Together, our results showed that LLLT abolishes FA-induced neutrophilic lung inflammation by a reduction of the inflammatory cytokines and mast cell degranulation. This study may provide important information about the mechanisms of LLLT in lung inflammation induced by a pollutant.

  9. Chronic lung allograft dysfunction after lung transplantation: novel insights into immunological mechanisms

    NARCIS (Netherlands)

    Budding, K.

    2016-01-01

    Lung transplantation (LTx) is the final treatment option for patients suffering from end-stage lung diseases. Survival after LTx is hampered by the development of chronic lung allograft dysfunction which presents itself in an obstructive form as the bronchiolitis obliterans syndrome (BOS). BOS is ha

  10. Hypoxic Epithelial Necrosis Triggers Neutrophilic Inflammation via IL-1 Receptor Signaling in Cystic Fibrosis Lung Disease

    OpenAIRE

    Fritzsching, Benedikt; Zhou-Suckow, Zhe; Trojanek, Joanna B.; Schubert, Susanne C.; Schatterny, Jolanthe; Hirtz, Stephanie; Agrawal, Raman; Muley, Thomas; Kahn, Nicolas; Sticht, Carsten; Gunkel, Nikolas; Welte, Tobias; Scott H Randell; Länger, Florian; Schnabel, Philipp

    2015-01-01

    Rationale: In many organs, hypoxic cell death triggers sterile neutrophilic inflammation via IL-1R signaling. Although hypoxia is common in airways from patients with cystic fibrosis (CF), its role in neutrophilic inflammation remains unknown. We recently demonstrated that hypoxic epithelial necrosis caused by airway mucus obstruction precedes neutrophilic inflammation in Scnn1b-transgenic (Scnn1b-Tg) mice with CF-like lung disease.

  11. Impact of inflammation, emphysema, and smoking cessation on V/Q in mouse models of lung obstruction

    Science.gov (United States)

    2014-01-01

    Background Chronic obstructive pulmonary disease (COPD) is known to greatly affect ventilation (V) and perfusion (Q) of the lung through pathologies such as inflammation and emphysema. However, there is little direct evidence regarding how these pathologies contribute to the V/Q mismatch observed in COPD and models thereof. Also, little is known regarding how smoking cessation affects V/Q relationships after inflammation and airspace enlargement have become established. To this end, we have quantified V/Q on a per-voxel basis using single photon emission computed tomography (SPECT) in mouse models of COPD and lung obstruction. Methods Three distinct murine models were used to investigate the impact of different pathologies on V/Q, as measured by SPECT. Lipopolysaccharide (LPS) was used to produce neutrophilic inflammation, porcine pancreatic elastase (PPE) was used to produce emphysema, and long-term cigarette smoke (CS) exposure and cessation were used to investigate the combination of these pathologies. Results CS exposure resulted in an increase in mononuclear cells and neutrophils, an increase in airspace enlargement, and an increase in V/Q mismatching. The inflammation produced by LPS was more robust and predominantly neutrophilic, compared to that of cigarette smoke; nevertheless, inflammation alone caused V/Q mismatching similar to that seen with long-term CS exposure. The emphysematous lesions caused by PPE administration were also capable of causing V/Q mismatch in the absence of inflammation. Following CS cessation, inflammatory cell levels returned to those of controls and, similarly, V/Q measures returned to normal despite evidence of persistent mild airspace enlargement. Conclusions Both robust inflammation and extensive airspace enlargement, on their own, were capable of producing V/Q mismatch. As CS cessation resulted in a return of V/Q mismatching and inflammatory cell counts to control levels, lung inflammation is likely a major contributor to V

  12. Effect of mesenchymal stem cells on inhibiting airway remodeling and airway inflammation in chronic asthma.

    Science.gov (United States)

    Ge, Xiahui; Bai, Chong; Yang, Jianming; Lou, Guoliang; Li, Qiang; Chen, Ruohua

    2013-07-01

    Previous studies proved that bone marrow-derived mesenchymal stem cells (BMSCs) could improve a variety of immune-mediated disease by its immunomodulatory properties. In this study, we investigated the effect on airway remodeling and airway inflammation by administrating BMSCs in chronic asthmatic mice. Forty-eight female BALB/c mice were randomly distributed into PBS group, BMSCs treatment group, BMSCs control group, and asthmatic group. The levels of cytokine and immunoglobulin in serum and bronchoalveolar lavage fluid were detected by enzyme-linked immunosorbent assay. The number of CD4(+) CD25(+) regulatory T cells and morphometric analysis was determined by flow cytometry, hematoxylin-eosin, immunofluorescence staining, periodic-acid Schiff, and masson staining, respectively. We found that airway remodeling and airway inflammation were evident in asthmatic mice. Moreover, low level of IL-12 and high levels of IL-13, IL-4, OVA-specific IgG1, IgE, and IgG2a and the fewer number of CD4(+) CD25(+) regulatory T cells were present in asthmatic group. However, transplantation of BMSCs significantly decreased airway inflammation and airway remodeling and level of IL-4, OVA-specific IgE, and OVA-specific IgG1, but elevated level of IL-12 and the number of CD4 + CD25 + regulatory T cells in asthma (P cells in asthma, but not contribution to lung regeneration. PMID:23334934

  13. Bioactive Compounds Isolated from Microalgae in Chronic Inflammation and Cancer

    Directory of Open Access Journals (Sweden)

    Elena Talero

    2015-09-01

    Full Text Available The risk of onset of cancer is influenced by poorly controlled chronic inflammatory processes. Inflammatory diseases related to cancer development include inflammatory bowel disease, which can lead to colon cancer, or actinic keratosis, associated with chronic exposure to ultraviolet light, which can progress to squamous cell carcinoma. Chronic inflammatory states expose these patients to a number of signals with tumorigenic effects, including nuclear factor kappa B (NF-κB and mitogen-activated protein kinases (MAPK activation, pro-inflammatory cytokines and prostaglandins release and ROS production. In addition, the participation of inflammasomes, autophagy and sirtuins has been demonstrated in pathological processes such as inflammation and cancer. Chemoprevention consists in the use of drugs, vitamins, or nutritional supplements to reduce the risk of developing or having a recurrence of cancer. Numerous in vitro and animal studies have established the potential colon and skin cancer chemopreventive properties of substances from marine environment, including microalgae species and their products (carotenoids, fatty acids, glycolipids, polysaccharides and proteins. This review summarizes the main mechanisms of actions of these compounds in the chemoprevention of these cancers. These actions include suppression of cell proliferation, induction of apoptosis, stimulation of antimetastatic and antiangiogenic responses and increased antioxidant and anti-inflammatory activity.

  14. Surfactant Protein-D Inhibits Lung Inflammation Caused by Ventilation in Premature Newborn Lambs

    OpenAIRE

    Sato, Atsuyasu; Jeffrey A Whitsett; Scheule, Ronald K.; Ikegami, Machiko

    2010-01-01

    Rationale: Premature newborns frequently require manual ventilation for resuscitation during which lung injury occurs. Although surfactant protein (SP)-D regulates pulmonary inflammation, SP-D levels are low in the preterm lung. Commercial surfactants for treatment of respiratory distress syndrome do not contain SP-D.

  15. Montelukast versus Dexamethasone Treatment in a Guinea Pig Model of Chronic Pulmonary Neutrophilic Inflammation.

    Science.gov (United States)

    Abdel Kawy, Hala S

    2016-08-01

    Airway inflammation in chronic obstructive pulmonary disease (COPD) is refractory to corticosteroids and hence COPD treatment is hindered and insufficient. This study assessed the effects of oral treatment with Montelukast (10 and 30 mg/kg) or dexamethasone (20 mg/kg) for 20 days on COPD model induced by chronic exposure to lipopolysaccharide (LPS). Six groups of male guinea pigs were studied. Group 1: naïve group, group 2: exposed to saline nebulization. Groups 3, 4, 5, and 6: exposed to 9 nebulizations of LPS (30 μg/ml) for 1 hour, 48 hours apart with or without treatment with Montelukast or dexamethasone. Airway hyperreactivity (AHR) to methacholine (MCh), histopathological study and bronchoalveolar lavage fluid (BALF) as well as lung tissue analyses were performed 48 hours after the final exposure to LPS (day 20). LPS-induced pulmonary dysfunction was associated with increased neutrophil count, leukotriene (LT) B4, and tumor necrosis factor (TNF)-α in BALF. Moreover, there was an increase in malondialdehyde (MDA) level and a decrease in histone deacetylases(HDAC) activity in the lung tissue. Both Montelukast (10 or 30 mg /kg) and dexamethasone significantly reduced neutrophil count in BALF and inflammatory cells in lung parenchyma as well as TNF-α, and MDA levels. However, dexamethasone was more effective (p Montelukast, at a dose of 30 mg /kg, significantly reduced specific airway resistance after the 9th LPS exposure, attenuated AHR to MCh, decreased LTB4 and increased HDAC activity in comparison to dexamethasone. These results suggest that treatment with Montelukast can be useful in chronic airway inflammatory diseases including COPD poorly responsive to glucocorticoids. PMID:26751767

  16. Quantitative assessment of global lung inflammation following radiation therapy using FDG PET/CT: a pilot study

    Energy Technology Data Exchange (ETDEWEB)

    Abdulla, Sarah; Salavati, Ali; Saboury, Babak; Torigian, Drew A. [University of Pennsylvania, and Hospital of the University of Pennsylvania, Department of Radiology, Perelman School of Medicine, Philadelphia, PA (United States); Basu, Sandip [Bhabha Atomic Research Center, Tata Memorial Center Annexe, Radiation Medicine Center, Bombay (India); Alavi, Abass [University of Pennsylvania, and Hospital of the University of Pennsylvania, Department of Radiology, Perelman School of Medicine, Philadelphia, PA (United States); Hospital of the University of Pennsylvania, Department of Radiology, Division of Nuclear Medicine, Philadelphia, PA (United States)

    2014-02-15

    Radiation pneumonitis is the most severe dose-limiting complication in patients receiving thoracic radiation therapy. The aim of this study was to quantify global lung inflammation following radiation therapy using FDG PET/CT. We studied 20 subjects with stage III non-small-cell lung carcinoma who had undergone FDG PET/CT imaging before and after radiation therapy. On all PET/CT studies, the sectional lung volume (sLV) of each lung was calculated from each slice by multiplying the lung area by slice thickness. The sectional lung glycolysis (sLG) was calculated by multiplying the sLV and the lung sectional mean standardized uptake value (sSUVmean) on each slice passing through the lung. The lung volume (LV) was calculated by adding all sLVs from the lung, and the global lung glycolysis (GLG) was calculated by adding all sLGs from the lung. Finally, the lung SUVmean was calculated by dividing the GLG by the LV. The amount of inflammation in the lung parenchyma directly receiving radiation therapy was calculated by subtracting tumor measurements from GLG. In the lung directly receiving radiation therapy, the lung parenchyma SUVmean and global lung parenchymal glycolysis were significantly increased following therapy. In the contralateral lung (internal control), no significant changes were observed in lung SUVmean or GLG following radiation therapy. Global lung parenchymal glycolysis and lung parenchymal SUVmean may serve as potentially useful biomarkers to quantify lung inflammation on FDG PET/CT following thoracic radiation therapy. (orig.)

  17. Environmental and genetic risk factors and gene-environment interactions in the pathogenesis of chronic obstructive lung disease.

    OpenAIRE

    Walter, R.; Gottlieb, D. J.; O'Connor, G T

    2000-01-01

    Current understanding of the pathogenesis of chronic obstructive pulmonary disease (COPD), a source of substantial morbidity and mortality in the United States, suggests that chronic inflammation leads to the airways obstruction and parenchymal destruction that characterize this condition. Environmental factors, especially tobacco smoke exposure, are known to accelerate longitudinal decline of lung function, and there is substantial evidence that upregulation of inflammatory pathways plays a ...

  18. Chronic pancreatitis: Maldigestion, intestinal ecology and intestinal inflammation

    Institute of Scientific and Technical Information of China (English)

    Raffaele Pezzilli

    2009-01-01

    Exocrine pancreatic insufficiency caused by chronic pancreatitis results from various factors whichregulate digestion and absorption of nutrients. Pancreatic function has been extensively studied over the last 40 years, even if some aspects of secretion and gastrointestinal adaptation are not completely understood. The main clinical manifestations of exocrine pancreatic insufficiency are fat malabsorption, known as steatorrhea, which consists of fecal excretion of more than 6 g of fat per day, weightloss, abdominal discomfort and abdominal swelling sensation. Fat malabsorption also results in a deficit of fat-soluble vitamins (A, D, E and K) with consequent clinical manifestations. The relationships between pancreatic maldigestion, intestinal ecology and intestinal inflammation have not received particular attention, even if in clinical practice these mechanisms may be responsible for the low efficacy of pancreatic extracts in abolishing steatorrhea in some patients. The best treatments for pancreatic maldigestion should be re-evaluated, taking into account not only the correction of pancreatic insufficiency using pancreatic extracts and the best duodenal pH to permit optimal efficacy of these extracts, but we also need to consider other therapeutic approaches including the decontamination of intestinal lumen, supplementation of bile acids and, probably, the use of probiotics which may attenuate intestinal inflammation

  19. HRCT diagnosis in the evaluation of chronic middle ear inflammation

    Energy Technology Data Exchange (ETDEWEB)

    Yu, Jung Sik; Kim, Dong Ik; Suh, Jung Ho; Chung, Tae Sub [College of Medicine, Yonsei Univ., Seoul (Korea, Republic of)

    1990-10-15

    Though the preoperative high-resolution computed tomographic (HRCT) evaluation of the patients with chronic middle ear inflammation, the nature and potential complications of the lesions can be evaluated more accurately than previous imaging modalities. We retrospectively reviewed the HRCT findings of chronic middle ear inflammation in 50 surgically proven cases during recent 2 years. We also compared findings of HRCT and otologic surgery in order to know the diagnostic ability of HRCT about the true nature and extent of soft tissue inflammatory masses within the middle ear and various complications. The results obtained were as follows : 1. HRCT demonstrated the soft tissue inflammatory lesions in the middle ear cavity in all 50 cases. Among these, 32 cases were confirmed to have cholesteatoma, and 12 cases of granulations tissue including 2 cases of cholestrol granuloma, 3 cases of thickened mucosa and 3 cases of inflammatory exude were verified respectively. 2. Among the 32 cases of cholesteatoma, HRCT showed the ossicular erosion in 87% and other complications in 38% of cases. The types of cholesteatoma can be predicted according to the site and extension of soft tissue mass except in 6 cases. 3. Among the 12 cases of granulation tissue, HRCT also showed the erosion of ossicles in 50% and facial nerve canal in 17%. 4. Pars flaccida type cholesteatomas (21 cases) were most frequently noted in atticoantral area (67%) and pars tensa type (4 cases) in mesotympanum (75%). 5. Incus body and malleus head were the most vulnerable portions of bony erosion in pars flaccida type (10/21). 6. We met some difficulty in differentiation of the soft tissue inflammatory mass in 7 cases.

  20. Pneumonectomy for chronic inflammatory lung disease: indications and complications

    Institute of Scientific and Technical Information of China (English)

    NIE Gang; LIU Guo-jun; Jean Deslauriers; FAN Zhi-min

    2010-01-01

    @@ Chronic inflammatory lung disease is a common health problem and often treated with potent antibiotics, anti-tuberculosis drugs, and antifungal agents. However, in case of medical therapy failure, surgical treatment has been often considered as an effective procedure.

  1. Exercise Training as a Treatment for Chronic Inflammation in the Elderly

    OpenAIRE

    Nicklas, Barbara J; Brinkley, Tina E.

    2009-01-01

    Persistent, sub-clinical inflammation predisposes to chronic disease, as well as the development of sarcopenia and disability, in frail elderly. Thus, the inflammatory pathway is a potential target for interventions to reduce aging-related disease and disability. This article highlights emerging data suggesting that increasing physical activity could be effective for reducing chronic inflammation in the elderly.

  2. Physical Activity Protects the Human Brain against Metabolic Stress Induced by a Postprandial and Chronic Inflammation

    NARCIS (Netherlands)

    Pruimboom, Leo; Raison, Charles L.; Muskiet, Frits A. J.

    2015-01-01

    In recent years, it has become clear that chronic systemic low-grade inflammation is at the root of many, if not all, typically Western diseases associated with the metabolic syndrome. While much focus has been given to sedentary lifestyle as a cause of chronic inflammation, it is less often appreci

  3. The association between combined non-cystic fibrosis bronchiectasis and lung cancer in patients with chronic obstructive lung disease

    Directory of Open Access Journals (Sweden)

    Kim YW

    2015-05-01

    patients with squamous cell carcinoma (OR 0.11, 95% CI 0.03–0.49, P=0.001 and history of smoking (OR 0.27, 95% CI 0.12–0.57, P<0.001. However, the severity and location of bronchiectasis were not associated with the risk of lung cancer.Conclusion: Interestingly, the concomitant presence of bronchiectasis in COPD patients was associated with a lower risk of lung cancer.Keywords: bronchiectasis, lung cancer, chronic inflammation, COPD

  4. Phenotypes selected during chronic lung infection in cystic fibrosis patients

    DEFF Research Database (Denmark)

    Ciofu, Oana; Mandsberg, Lotte F; Wang, Hengzhuang;

    2012-01-01

    During chronic lung infection of patients with cystic fibrosis, Pseudomonas aeruginosa can survive for long periods of time under the challenging selective pressure imposed by the immune system and antibiotic treatment as a result of its biofilm mode of growth and adaptive evolution mediated...... the importance of biofilm prevention strategies by early aggressive antibiotic prophylaxis or therapy before phenotypic diversification during chronic lung infection of patients with cystic fibrosis....

  5. Epithelial-Derived Inflammation Disrupts Elastin Assembly and Alters Saccular Stage Lung Development.

    Science.gov (United States)

    Benjamin, John T; van der Meer, Riet; Im, Amanda M; Plosa, Erin J; Zaynagetdinov, Rinat; Burman, Ankita; Havrilla, Madeline E; Gleaves, Linda A; Polosukhin, Vasiliy V; Deutsch, Gail H; Yanagisawa, Hiromi; Davidson, Jeffrey M; Prince, Lawrence S; Young, Lisa R; Blackwell, Timothy S

    2016-07-01

    The highly orchestrated interactions between the epithelium and mesenchyme required for normal lung development can be disrupted by perinatal inflammation in preterm infants, although the mechanisms are incompletely understood. We used transgenic (inhibitory κB kinase β transactivated) mice that conditionally express an activator of the NF-κB pathway in airway epithelium to investigate the impact of epithelial-derived inflammation during lung development. Epithelial NF-κB activation selectively impaired saccular stage lung development, with a phenotype comprising rapidly progressive distal airspace dilation, impaired gas exchange, and perinatal lethality. Epithelial-derived inflammation resulted in disrupted elastic fiber organization and down-regulation of elastin assembly components, including fibulins 4 and 5, lysyl oxidase like-1, and fibrillin-1. Fibulin-5 expression by saccular stage lung fibroblasts was consistently inhibited by treatment with bronchoalveolar lavage fluid from inhibitory κB kinase β transactivated mice, Escherichia coli lipopolysaccharide, or tracheal aspirates from preterm infants exposed to chorioamnionitis. Expression of a dominant NF-κB inhibitor in fibroblasts restored fibulin-5 expression after lipopolysaccharide treatment, whereas reconstitution of fibulin-5 rescued extracellular elastin assembly by saccular stage lung fibroblasts. Elastin organization was disrupted in saccular stage lungs of preterm infants exposed to systemic inflammation. Our study reveals a critical window for elastin assembly during the saccular stage that is disrupted by inflammatory signaling and could be amenable to interventions that restore elastic fiber assembly in the developing lung. PMID:27181406

  6. Lung inflammation does not affect the clearance kinetics of lipid nanocapsules following pulmonary administration.

    Science.gov (United States)

    Patel, Aateka; Woods, A; Riffo-Vasquez, Yanira; Babin-Morgan, Anna; Jones, Marie-Christine; Jones, Stuart; Sunassee, Kavitha; Clark, Stephen; T M de Rosales, Rafael; Page, Clive; Spina, Domenico; Forbes, Ben; Dailey, Lea Ann

    2016-08-10

    Lipid nanocapsules (LNCs) are semi-rigid spherical capsules with a triglyceride core that present a promising formulation option for the pulmonary delivery of drugs with poor aqueous solubility. Whilst the biodistribution of LNCs of different size has been studied following intravenous administration, the fate of LNCs following pulmonary delivery has not been reported. We investigated quantitatively whether lung inflammation affects the clearance of 50nm lipid nanocapsules, or is exacerbated by their pulmonary administration. Studies were conducted in mice with lipopolysaccharide-induced lung inflammation compared to healthy controls. Particle deposition and nanocapsule clearance kinetics were measured by single photon emission computed tomography/computed tomography (SPECT/CT) imaging over 48 h. A significantly lower lung dose of (111)In-LNC50 was achieved in the lipopolysaccharide (LPS)-treated animals compared with healthy controls (p<0.001). When normalised to the delivered lung dose, the clearance kinetics of (111)In-LNC50 from the lungs fit a first order model with an elimination half-life of 10.5±0.9h (R(2)=0.995) and 10.6±0.3h (R(2)=1.000) for healthy and inflamed lungs respectively (n=3). In contrast, (111)In-diethylene triamine pentaacetic acid (DTPA), a small hydrophilic molecule, was cleared rapidly from the lungs with the majority of the dose absorbed within 20min of administration. Biodistribution to lungs, stomach-intestine, liver, trachea-throat and blood at the end of the imaging period was unaltered by lung inflammation. This study demonstrated that lung clearance and whole body distribution of lipid nanocapsules were unaffected by the presence of acute lung inflammation. PMID:27180635

  7. Salt Intake Is Associated with Inflammation in Chronic Heart Failure

    Directory of Open Access Journals (Sweden)

    Alper Azak

    2015-09-01

    Full Text Available Background: Chronic Heart Failure (CHF is highly prevalent and is associated with high morbidity and mortality rates. It has been well established that excessive intake of sodium chloride (salt induced hypertension in some populations. Although salt seems to induce cardiovascular diseases through elevation of blood pressure, it has also been indicated that salt can induce cardiovascular diseases independently from blood pressure elevation. Objectives: The present study aimed to evaluate the association between salt consumption and inflammation in CHF patients. Patients and Methods: This study was conducted on 86 patients between 18 and 65 years old who were diagnosed with New York Heart Association (NYHA functional class I and II heart failure. Salt intake was calculated by using 24 hour urine sodium excretion. Besides, the association between inflammation and daily salt intake was evaluated regarding C - reactive protein (CPR, High sensitive CRP (HsCPR, Erythrocyte Sedimentation Rate (ESR, and ferritin and fibrinogen levels using Pearson correlation analysis. Results: Our results showed a statistically significant difference between the low (n = 41 and high (n = 45 salt intake groups in terms of serum HsCRP levels (5.21 ± 2.62 vs. 6.36 ± 2.64 (P < 0.048. Additionally, a significant correlation was observed between the amount of salt consumption and HsCRP levels. In this study, daily salt consumption of the enrolled patients was 8.53 gram/day. The medications and even the blood pressures were similar in the two groups, but daily pill count, prevalence of hypertension, and coronary heart disease were higher in the high salt intake group; however, the differences were not statistically significant (P = 0.065. Also, no significant difference was observed between the groups concerning the inflammation markers, such as CRP, ESR, ferritin, and fibrinogen. Conclusions: Neurohumoral and inflammatory factors are thought to contribute to high mortality

  8. Balance impairment and systemic inflammation in chronic obstructive pulmonary disease

    Directory of Open Access Journals (Sweden)

    Tudorache E

    2015-09-01

    Full Text Available Emanuela Tudorache,1 Cristian Oancea,1 Claudiu Avram,2 Ovidiu Fira-Mladinescu,1 Lucian Petrescu,3 Bogdan Timar4 1Department of Pulmonology, University of Medicine and Pharmacy “Victor Babes”, 2Physical Education and Sport Faculty, West University of Timisoara, 3Department of Cardiology, University of Medicine and Pharmacy “Victor Babes”, 4Department of Biostatistics and Medical Informatics, University of Medicine and Pharmacy “Victor Babes”, Timisoara, Romania Background/purpose: Chronic obstructive pulmonary disease (COPD, especially in severe forms, is commonly associated with systemic inflammation and balance impairment. The aim of our study was to evaluate the impact on equilibrium of stable and exacerbation (acute exacerbation of COPD [AECOPD] phases of COPD and to investigate if there is a connection between lower extremity muscle weakness and systemic inflammation.Methods: We enrolled 41 patients with COPD (22 stable and 19 in AECOPD and 20 healthy subjects (control group, having no significant differences regarding the anthropometric data. We analyzed the differences in balance tests scores: Falls Efficacy Scale-International (FES-I questionnaire, Berg Balance Scale (BBS, Timed Up and Go (TUG test, Single Leg Stance (SLS, 6-minute walking distance (6MWD, isometric knee extension (IKE between these groups, and also the correlation between these scores and inflammatory biomarkers.Results: The presence and severity of COPD was associated with significantly decreased score in IKE (P<0.001, 6MWD (P<0.001, SLS (P<0.001, and BBS (P<0.001, at the same time noting a significant increase in median TUG score across the studied groups (P<0.001. The AECOPD group vs stable group presented a significant increase in high-sensitive C-reactive protein (hs-CRP levels (10.60 vs 4.01; P=0.003 and decrease in PaO2 (70.1 vs 59.1; P<0.001. We observed that both IKE scores were significantly and positive correlated with all the respiratory volumes

  9. Chronic administration of Abarema cochliacarpos attenuates colonic inflammation in rats

    Directory of Open Access Journals (Sweden)

    Maria Silene da Silva

    2011-08-01

    Full Text Available Inflammatory bowel diseases are characterized by a chronic clinical course of relapse and remission associated with self-destructive inflammation of the gastrointestinal tract. Active extracts from plants have emerged as natural potential candidates for its treatment. Abarema cochliacarpos (Gomes Barneby & Grimes, Fabaceae (Barbatimão, is a native medicinal plant in to Brazil. Previously we have demonstrated in an acute colitis model a marked protective effect of a butanolic extract, so we decided to assess its anti-inflammatory effect in a chronic ulcerative colitis model induced by trinitrobenzensulfonic acid (TNBS. Abarema cochliacarpos (150 mg/day, v.o. was administered for fourteen consecutive days. This treatment decreased significantly macroscopic damage as compared with TNBS. Histological analysis showed that the extract improved the microscopic structure. Myeloperoxidase activity (MPO was significantly decreased. Study of cytokines showed that TNF-α was diminished and IL-10 level was increased after Abarema cochliacarpos treatment. In order to elucidate inflammatory mechanisms, expression of cyclooxygenase (COX-2 and nitric oxide synthase (iNOS were studied showing a significant downregulation. In addition, there was reduction in the JNK and p-38 activation. Finally, IκB degradation was blocked by Abarema cochliacarpos treatment being consistent with an up-regulation of the NF-kappaB-binding activity. These results reinforce the anti-inflammatory effects described previously suggesting that Abarema cochliacarpos could provide a source for the search for new anti-inflammatory compounds useful in ulcerative colitis treatment.

  10. Progress on Clinical Study of Acupuncture Treatment for Chronic Pelvic Inflammation

    Institute of Scientific and Technical Information of China (English)

    ZHAO Wen-jie; HUANG Guo-qi

    2008-01-01

    @@ Chronic pelvic inflammation is mostly caused byincomplete treatment of acute pelvic inflammation orby transference from pathologic condition due to poorbody constitution, including chronic endometritis,chronic salpingo-oophoritis and chronic inflammationof connective tissue, and is a commonly andfrequently encountered disease in the gynecologydepartment. Due to long duration, intractablecondition and high recurrent rate, it is also acommonly encountered reason to induce heterotopicpregnancy, sterility, pelvic pain and pelvic adhesivediseases. In the investigative study on the domesticliterature about acupuncture treatment of chronicpelvic inflammation in the recent five years, theauthor hopes to summarize the information forreference in the clinical treatment and to point outsome issues existing in the current clinical study.

  11. Critical role for IL-18 in spontaneous lung inflammation caused by autophagy deficiency.

    Science.gov (United States)

    Abdel Fattah, Elmoataz; Bhattacharya, Abhisek; Herron, Alan; Safdar, Zeenat; Eissa, N Tony

    2015-06-01

    Autophagy is an important component of the immune response. However, the functions of autophagy in human diseases are much less understood. We studied biological consequences of autophagy deficiency in mice lacking the essential autophagy gene Atg7 or Atg5 in myeloid cells. Surprisingly, these mice presented with spontaneous sterile lung inflammation, characterized by marked recruitment of inflammatory cells, submucosal thickening, goblet cell metaplasia, and increased collagen content. Lung inflammation was associated with increase in several proinflammatory cytokines in the bronchoalveolar lavage and in serum. This inflammation was largely driven by IL-18 as a result of constitutive inflammasome activation. Following i.p. LPS injection, autophagy-deficient mice had higher levels of proinflammatory cytokines in lungs and in serum, as well as increased mortality, than control mice. Intranasal bleomycin challenge exacerbated lung inflammation in autophagy-deficient mice and produced more severe fibrotic changes than in control mice. These results uncover a new and important role for autophagy as negative regulator of lung inflammation.

  12. Caffeine Mitigates Lung Inflammation Induced by Ischemia-Reperfusion of Lower Limbs in Rats

    Directory of Open Access Journals (Sweden)

    Wei-Chi Chou

    2015-01-01

    Full Text Available Reperfusion of ischemic limbs can induce inflammation and subsequently cause acute lung injury. Caffeine, a widely used psychostimulant, possesses potent anti-inflammatory capacity. We elucidated whether caffeine can mitigate lung inflammation caused by ischemia-reperfusion (IR of the lower limbs. Adult male Sprague-Dawley rats were randomly allocated to receive IR, IR plus caffeine (IR + Caf group, sham-operation (Sham, or sham plus caffeine (n=12 in each group. To induce IR, lower limbs were bilaterally tied by rubber bands high around each thigh for 3 hours followed by reperfusion for 3 hours. Caffeine (50 mg/kg, intraperitoneal injection was administered immediately after reperfusion. Our histological assay data revealed characteristics of severe lung inflammation in the IR group and mild to moderate characteristic of lung inflammation in the IR + Caf group. Total cells number and protein concentration in bronchoalveolar lavage fluid of the IR group were significantly higher than those of the IR + Caf group (P<0.001 and P=0.008, resp.. Similarly, pulmonary concentrations of inflammatory mediators (tumor necrosis factor-α, interleukin-1β, and macrophage inflammatory protein-2 and pulmonary myeloperoxidase activity of the IR group were significantly higher than those of the IR + Caf group (all P<0.05. These data clearly demonstrate that caffeine could mitigate lung inflammation induced by ischemia-reperfusion of the lower limbs.

  13. DISTINCT PHENOTYPES OF INFILTRATING CELLS DURING ACUTE AND CHRONIC LUNG REJECTION IN HUMAN HEART-LUNG TRANSPLANTS

    NARCIS (Netherlands)

    WINTER, JB; CLELLAND, C; GOUW, ASH; PROP, J

    1995-01-01

    To differentiate between acute and chronic lung rejection in an early stage, phenotypes of infiltrating inflammatory cells were analyzed in 34 transbronchial biopsies (TBBs) of 24 patients after heart-lung transplantation. TBBs were taken during during acute lung rejection and chronic lung rejection

  14. Attenuation of acute lung inflammation induced by cigarette smoke in CXCR3 knockout mice

    Directory of Open Access Journals (Sweden)

    Cheng Deyun

    2008-12-01

    Full Text Available Abstract Background CD8+ T cells may participate in cigarette smoke (CS induced-lung inflammation in mice. CXCL10/IP-10 (IFNγ-inducible protein 10 and CXCL9/Mig (monokine induced by IFN-γ are up-regulated in CS-induced lung injury and may attract T-cell recruitment to the lung. These chemokines together with CXCL11/ITAC (IFN-inducible T-cell alpha chemoattractant are ligands for the chemokine receptor CXCR3 which is preferentially expressed chiefly in activated CD8+ T cells. The purpose of this investigation was to study the contribution of CXCR3 to acute lung inflammation induced by CS using CXCR3 knockout (KO mice. Methods Mice (n = 8 per group were placed in a closed plastic box connected to a smoke generator and were exposed whole body to the tobacco smoke of five cigarettes four times a day for three days. Lung pathological changes, expression of inflammatory mediators in bronchoalveolar lavage (BAL fluid and lungs at mRNA and protein levels, and lung infiltration of CD8+ T cells were compared between CXCR3-/- mice and wild type (WT mice. Results Compared with the WT littermates, CXCR3 KO mice showed less CS-induced lung inflammation as evidenced by less infiltration of inflammatory cells in airways and lung tissue, particularly fewer CD8+ T cells, lower levels of IFNγ and CXCR3 ligands (particularly CXCL10. Conclusion Our findings show that CXCR3 is important in promoting CD8+ T cell recruitment and in initiating IFNγ and CXCL10 release following CS exposure. CXCR3 may represent a promising therapeutic target for acute lung inflammation induced by CS.

  15. Role of TNF-α in lung tight junction alteration in mouse model of acute lung inflammation

    Directory of Open Access Journals (Sweden)

    Cuzzocrea Salvatore

    2007-10-01

    Full Text Available Abstract In the present study, we used tumor necrosis factor-R1 knock out mice (TNF-αR1KO to understand the roles of TNF-α on epithelial function in models of carrageenan-induced acute lung inflammation. In order to elucidate whether the observed anti-inflammatory status is related to the inhibition of TNF-α, we also investigated the effect of etanercept, a TNF-α soluble receptor construct, on lung TJ function. Pharmacological and genetic TNF-α inhibition significantly reduced the degree of (1 TNF-α production in pleural exudates and in the lung tissues, (2 the inflammatory cell infiltration in the pleural cavity as well as in the lung tissues (evaluated by MPO activity, (3 the alteration of ZO-1, Claudin-2, Claudin-4, Claudin-5 and β-catenin (immunohistochemistry and (4 apoptosis (TUNEL staining, Bax, Bcl-2 expression. Taken together, our results demonstrate that inhibition of TNF-α reduces the tight junction permeability in the lung tissues associated with acute lung inflammation, suggesting a possible role of TNF-α on lung barrier dysfunction.

  16. Balance impairment and systemic inflammation in chronic obstructive pulmonary disease

    Science.gov (United States)

    Tudorache, Emanuela; Oancea, Cristian; Avram, Claudiu; Fira-Mladinescu, Ovidiu; Petrescu, Lucian; Timar, Bogdan

    2015-01-01

    Background/purpose Chronic obstructive pulmonary disease (COPD), especially in severe forms, is commonly associated with systemic inflammation and balance impairment. The aim of our study was to evaluate the impact on equilibrium of stable and exacerbation (acute exacerbation of COPD [AECOPD]) phases of COPD and to investigate if there is a connection between lower extremity muscle weakness and systemic inflammation. Methods We enrolled 41 patients with COPD (22 stable and 19 in AECOPD) and 20 healthy subjects (control group), having no significant differences regarding the anthropometric data. We analyzed the differences in balance tests scores: Falls Efficacy Scale-International (FES-I) questionnaire, Berg Balance Scale (BBS), Timed Up and Go (TUG) test, Single Leg Stance (SLS), 6-minute walking distance (6MWD), isometric knee extension (IKE) between these groups, and also the correlation between these scores and inflammatory biomarkers. Results The presence and severity of COPD was associated with significantly decreased score in IKE (P<0.001), 6MWD (P<0.001), SLS (P<0.001), and BBS (P<0.001), at the same time noting a significant increase in median TUG score across the studied groups (P<0.001). The AECOPD group vs stable group presented a significant increase in high-sensitive C-reactive protein (hs-CRP) levels (10.60 vs 4.01; P=0.003) and decrease in PaO2 (70.1 vs 59.1; P<0.001). We observed that both IKE scores were significantly and positive correlated with all the respiratory volumes. In both COPD groups, we observed that fibrinogen reversely and significantly correlated with the 6MWD, and FES-I questionnaire is correlated positively with TUG test. Hs-CRP correlated reversely with the walking test and SLS test, while correlating positively with TUG test and FES-I questionnaire. Conclusion According to this study, COPD in advanced and acute stages is associated with an increased history of falls, systemic inflammation, balance impairment, and lower extremity

  17. The Lung Microbiome, Immunity, and the Pathogenesis of Chronic Lung Disease.

    Science.gov (United States)

    O'Dwyer, David N; Dickson, Robert P; Moore, Bethany B

    2016-06-15

    The development of culture-independent techniques for microbiological analysis has uncovered the previously unappreciated complexity of the bacterial microbiome at various anatomic sites. The microbiome of the lung has relatively less bacterial biomass when compared with the lower gastrointestinal tract yet displays considerable diversity. The composition of the lung microbiome is determined by elimination, immigration, and relative growth within its communities. Chronic lung disease alters these factors. Many forms of chronic lung disease demonstrate exacerbations that drive disease progression and are poorly understood. Mounting evidence supports ways in which microbiota dysbiosis can influence host defense and immunity, and in turn may contribute to disease exacerbations. Thus, the key to understanding the pathogenesis of chronic lung disease may reside in deciphering the complex interactions between the host, pathogen, and resident microbiota during stable disease and exacerbations. In this brief review we discuss new insights into these labyrinthine relationships. PMID:27260767

  18. Intrapulmonary Delivery of Ethyl Pyruvate Attenuates Lipopolysaccharide : and Lipoteichoic Acid-Induced Lung Inflammation in Vivo

    OpenAIRE

    van Zoelen, Marieke A.D.; de Vos, Alex F.; Larosa, Gregory J.; Draing, Christian; Aulock, Sonja von; van der Poll, Tom

    2007-01-01

    Ethyl pyruvate (EP) is a stable pyruvate derivative that has been shown to exert anti-inflammatory effects in various models of systemic inflammation including endotoxemia. We here sought to determine the local effects of EP, after intrapulmonary delivery, in models of lung inflammation induced by instillation via the airways of either lipopolysaccharide (LPS, a constituent of the gram-negative bacterial cell wall) or lipoteichoic acid (LTA, a component of the gram-positive bacterial cell wal...

  19. Danaparoid sodium inhibits systemic inflammation and prevents endotoxin-induced acute lung injury in rats

    OpenAIRE

    Hagiwara, Satoshi; Iwasaka, Hideo; Hidaka, Seigo; Hishiyama, Sohei; Noguchi, Takayuki

    2008-01-01

    Introduction Systemic inflammatory mediators, including high mobility group box 1 (HMGB1), play an important role in the development of sepsis. Anticoagulants, such as danaparoid sodium (DA), may be able to inhibit sepsis-induced inflammation, but the mechanism of action is not well understood. We hypothesised that DA would act as an inhibitor of systemic inflammation and prevent endotoxin-induced acute lung injury in a rat model. Methods We used male Wistar rats. Animals in the intervention ...

  20. Lung function and airway inflammation monitoring after hematopoietic stem cell transplantation.

    OpenAIRE

    Moermans, Catherine; Poulet, Christophe; Henket, Monique; Bonnet, Christophe; WILLEMS, Evelyne; Baron, Frédéric; Beguin, Yves; Louis, Renaud

    2013-01-01

    Background Induced sputum is a non-invasive method to investigate airway inflammation, which has been used to assess pulmonary inflammatory diseases. However, this procedure has not been studied in the context of hematopoietic stem cell transplantation (HSCT). Methods We monitored lung function in 182 patients who underwent HSCT and measured airway inflammation by sputum induction in 80 of them. We prospectively measured FEV1, FVC, DLCO, KCO, TLC, RV, exhaled nitric oxide (FeNO) as ...

  1. The cardiopulmonary continuum systemic inflammation as 'common soil' of heart and lung disease

    NARCIS (Netherlands)

    Ukena, Christian; Mahfoud, Felix; Kindermann, Michael; Kindermann, Ingrid; Bals, Robert; Voors, Adriaan A.; van Veldhuisen, Dirk J.; Boehm, Michael

    2010-01-01

    Coronary artery disease (CAD), chronic heart failure (CHF) or chronic obstructive pulmonary disease (COPD) occur commonly in the presence of each other and are associated with similar systemic inflammatory reactions. Inflammation plays a central role in the pathogenesis of these diseases. C-reactive

  2. A novel anti-inflammatory and pro-resolving role for resolvin D1 in acute cigarette smoke-induced lung inflammation.

    Directory of Open Access Journals (Sweden)

    Hsi-Min Hsiao

    Full Text Available Cigarette smoke is a profound pro-inflammatory stimulus that contributes to acute lung injuries and to chronic lung disease including COPD (emphysema and chronic bronchitis. Until recently, it was assumed that resolution of inflammation was a passive process that occurred once the inflammatory stimulus was removed. It is now recognized that resolution of inflammation is a bioactive process, mediated by specialized lipid mediators, and that normal homeostasis is maintained by a balance between pro-inflammatory and pro-resolving pathways. These novel small lipid mediators, including the resolvins, protectins and maresins, are bioactive products mainly derived from dietary omega-3 and omega-6 polyunsaturated fatty acids (PUFA. We hypothesize that resolvin D1 (RvD1 has potent anti-inflammatory and pro-resolving effects in a model of cigarette smoke-induced lung inflammation.Primary human lung fibroblasts, small airway epithelial cells and blood monocytes were treated with IL-1β or cigarette smoke extract in combination with RvD1 in vitro, production of pro-inflammatory mediators was measured. Mice were exposed to dilute mainstream cigarette smoke and treated with RvD1 either concurrently with smoke or after smoking cessation. The effects on lung inflammation and lung macrophage populations were assessed.RvD1 suppressed production of pro-inflammatory mediators by primary human cells in a dose-dependent manner. Treatment of mice with RvD1 concurrently with cigarette smoke exposure significantly reduced neutrophilic lung inflammation and production of pro-inflammatory cytokines, while upregulating the anti-inflammatory cytokine IL-10. RvD1 promoted differentiation of alternatively activated (M2 macrophages and neutrophil efferocytosis. RvD1 also accelerated the resolution of lung inflammation when given after the final smoke exposure.RvD1 has potent anti-inflammatory and pro-resolving effects in cells and mice exposed to cigarette smoke. Resolvins

  3. The triterpenoid CDDO limits inflammation in preclinical models of cystic fibrosis lung disease

    OpenAIRE

    Nichols, David P.; Ziady, Assem G.; Shank, Samuel L.; Eastman, Jean F.; Davis, Pamela B.

    2009-01-01

    Excessive inflammation in cystic fibrosis (CF) lung disease is a contributor to progressive pulmonary decline. Effective and well-tolerated anti-inflammatory therapy may preserve lung function, thereby improving quality and length of life. In this paper, we assess the anti-inflammatory effects of the synthetic triterpenoid 2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oic acid (CDDO) in preclinical models of CF airway inflammation. In our experiments, mice carrying the R117H Cftr mutation have sig...

  4. Linalool inhibits cigarette smoke-induced lung inflammation by inhibiting NF-κB activation.

    Science.gov (United States)

    Ma, Jianqun; Xu, Hai; Wu, Jun; Qu, Changfa; Sun, Fenglin; Xu, Shidong

    2015-12-01

    Linalool, a natural compound that exists in the essential oils of several aromatic plants species, has been reported to have anti-inflammatory effects. However, the effects of linalool on cigarette smoke (CS)-induced acute lung inflammation have not been reported. In the present study, we investigated the protective effects of linalool on CS-induced acute lung inflammation in mice. Linalool was given i.p. to mice 2h before CS exposure daily for five consecutive days. The numbers of macrophages and neutrophils in bronchoalveolar lavage fluid (BALF) were measured. The production of TNF-α, IL-6, IL-1β, IL-8 and MCP-1 were detected by ELISA. The expression of NF-κB was detected by Western blotting. Our results showed that treatment of linalool significantly attenuated CS-induced lung inflammation, coupled with inhibited the infiltration of inflammatory cells and TNF-α, IL-6, IL-1β, IL-8 and MCP-1 production. Meanwhile, treatment of linalool inhibited CS-induced lung MPO activity and pathological changes. Furthermore, linalool suppressed CS-induced NF-κB activation in a dose-dependent manner. In conclusion, our results demonstrated that linalool protected against CS-induced lung inflammation through inhibiting CS-induced NF-κB activation.

  5. Stiffness-activated GEF-H1 expression exacerbates LPS-induced lung inflammation.

    Directory of Open Access Journals (Sweden)

    Isa Mambetsariev

    Full Text Available Acute lung injury (ALI is accompanied by decreased lung compliance. However, a role of tissue mechanics in modulation of inflammation remains unclear. We hypothesized that bacterial lipopolysacharide (LPS stimulates extracellular matrix (ECM production and vascular stiffening leading to stiffness-dependent exacerbation of endothelial cell (EC inflammatory activation and lung barrier dysfunction. Expression of GEF-H1, ICAM-1, VCAM-1, ECM proteins fibronectin and collagen, lysyl oxidase (LOX activity, interleukin-8 and activation of Rho signaling were analyzed in lung samples and pulmonary EC grown on soft (1.5 or 2.8 kPa and stiff (40 kPa substrates. LPS induced EC inflammatory activation accompanied by expression of ECM proteins, increase in LOX activity, and activation of Rho signaling. These effects were augmented in EC grown on stiff substrate. Stiffness-dependent enhancement of inflammation was associated with increased expression of Rho activator, GEF-H1. Inhibition of ECM crosslinking and stiffening by LOX suppression reduced EC inflammatory activation and GEF-H1 expression in response to LPS. In vivo, LOX inhibition attenuated LPS-induced expression of GEF-H1 and lung dysfunction. These findings present a novel mechanism of stiffness-dependent exacerbation of vascular inflammation and escalation of ALI via stimulation of GEF-H1-Rho pathway. This pathway represents a fundamental mechanism of positive feedback regulation of inflammation.

  6. Innate cellular sources of interleukin-17A regulate macrophage accumulation in cigarette- smoke-induced lung inflammation in mice.

    Science.gov (United States)

    Bozinovski, Steven; Seow, Huei Jiunn; Chan, Sheau Pyng Jamie; Anthony, Desiree; McQualter, Jonathan; Hansen, Michelle; Jenkins, Brendan J; Anderson, Gary P; Vlahos, Ross

    2015-11-01

    Cigarette smoke (CS) is the major cause of chronic obstructive pulmonary disease (COPD). Interleukin-17A (IL-17A) is a pivotal cytokine that regulates lung immunity and inflammation. The aim of the present study was to investigate how IL-17A regulates CS-induced lung inflammation in vivo. IL-17A knockout (KO) mice and neutralization of IL-17A in wild-type (WT) mice reduced macrophage and neutrophil recruitment and chemokine (C-C motif) ligand 2 (CCL2), CCL3 and matrix metalloproteinase (MMP)-12 mRNA expression in response to acute CS exposure. IL-17A expression was increased in non-obese diabetic (NOD) severe combined immunodeficiency SCID) mice with non-functional B- and T-cells over a 4-week CS exposure period, where macrophages accumulated to the same extent as in WT mice. Gene expression analysis by QPCR (quantitative real-time PCR) of isolated immune cell subsets detected increased levels of IL-17A transcript in macrophages, neutrophils and NK/NKT cells in the lungs of CS-exposed mice. In order to further explore the relative contribution of innate immune cellular sources, intracellular IL-17A staining was performed. In the present study, we demonstrate that CS exposure primes natural killer (NK), natural killer T (NKT) and γδ T-cells to produce more IL-17A protein and CS alone increased the frequency of IL17+ γδ T-cells in the lung, whereas IL-17A protein was not detected in macrophages and neutrophils. Our data suggest that activation of innate cellular sources of IL-17A is an essential mediator of macrophage accumulation in CS-exposed lungs. Targeting non-conventional T-cell sources of IL-17A may offer an alternative strategy to reduce pathogenic macrophages in COPD. PMID:26201093

  7. Alveolar inflammation in cystic fibrosis

    DEFF Research Database (Denmark)

    Ulrich, Martina; Worlitzsch, Dieter; Viglio, Simona;

    2010-01-01

    BACKGROUND: In infected lungs of the cystic fibrosis (CF) patients, opportunistic pathogens and mutated cystic fibrosis transmembrane conductance regulator protein (CFTR) contribute to chronic airway inflammation that is characterized by neutrophil/macrophage infiltration, cytokine release...

  8. Curcumin Attenuates Radiation-Induced Inflammation and Fibrosis in Rat Lungs

    OpenAIRE

    Cho, Yu Ji; Yi, Chin Ok; Jeon, Byeong Tak; Jeong, Yi Yeong; Kang, Gi Mun; Lee, Jung Eun; Roh, Gu Seob; Lee, Jong Deog

    2013-01-01

    A beneficial radioprotective agent has been used to treat the radiation-induced lung injury. This study was performed to investigate whether curcumin, which is known to have anti-inflammatory and antioxidant properties, could ameliorate radiation-induced pulmonary inflammation and fibrosis in irradiated lungs. Rats were given daily doses of intragastric curcumin (200 mg/kg) prior to a single irradiation and for 8 weeks after radiation. Histopathologic findings demonstrated that macrophage acc...

  9. Defective tryptophan catabolism underlies inflammation in mouse chronic granulomatous disease.

    Science.gov (United States)

    Romani, Luigina; Fallarino, Francesca; De Luca, Antonella; Montagnoli, Claudia; D'Angelo, Carmen; Zelante, Teresa; Vacca, Carmine; Bistoni, Francesco; Fioretti, Maria C; Grohmann, Ursula; Segal, Brahm H; Puccetti, Paolo

    2008-01-10

    Half a century ago, chronic granulomatous disease (CGD) was first described as a disease fatally affecting the ability of children to survive infections. Various milestone discoveries have since been made, from an insufficient ability of patients' leucocytes to kill microbes to the underlying genetic abnormalities. In this inherited disorder, phagocytes lack NADPH oxidase activity and do not generate reactive oxygen species, most notably superoxide anion, causing recurrent bacterial and fungal infections. Patients with CGD also suffer from chronic inflammatory conditions, most prominently granuloma formation in hollow viscera. The precise mechanisms of the increased microbial pathogenicity have been unclear, and more so the reasons for the exaggerated inflammatory response. Here we show that a superoxide-dependent step in tryptophan metabolism along the kynurenine pathway is blocked in CGD mice with lethal pulmonary aspergillosis, leading to unrestrained Vgamma1(+) gammadelta T-cell reactivity, dominant production of interleukin (IL)-17, defective regulatory T-cell activity and acute inflammatory lung injury. Although beneficial effects are induced by IL-17 neutralization or gammadelta T-cell contraction, complete cure and reversal of the hyperinflammatory phenotype are achieved by replacement therapy with a natural kynurenine distal to the blockade in the pathway. Effective therapy, which includes co-administration of recombinant interferon-gamma (IFN-gamma), restores production of downstream immunoactive metabolites and enables the emergence of regulatory Vgamma4(+) gammadelta and Foxp3(+) alphabeta T cells. Therefore, paradoxically, the lack of reactive oxygen species contributes to the hyperinflammatory phenotype associated with NADPH oxidase deficiencies, through a dysfunctional kynurenine pathway of tryptophan catabolism. Yet, this condition can be reverted by reactivating the pathway downstream of the superoxide-dependent step.

  10. Early immune response in susceptible and resistant mice strains with chronic Pseudomonas aeruginosa lung infection determines the type of T-helper cell response

    DEFF Research Database (Denmark)

    Moser, C; Hougen, H P; Song, Z;

    1999-01-01

    Most cystic fibrosis (CF) patients become chronically infected with Pseudomonas aeruginosa in the lungs. The infection is characterized by a pronounced antibody response and a persistant inflammation dominated by polymorphonuclear neutrophils. Moreover a high antibody response correlates...... with a poor prognosis. We speculated that a change from this Th2-like response to a Th1-like response might decrease the lung inflammation and thus improve the prognosis in CF patients. To investigate this, we infected C3H/HeN and BALB/c mice intratracheally with P. aeruginosa. In addition, we studied...... with chronic P. aeruginosa lung infection have a better disease outcome compared to the Th2-reacting BALB/c mice, indicating that a Th1 response might be beneficial in CF patients with chronic P. aeruginosa lung infection....

  11. Age-Related Macular Degeneration in the Aspect of Chronic Low-Grade Inflammation (Pathophysiological ParaInflammation

    Directory of Open Access Journals (Sweden)

    Małgorzata Nita

    2014-01-01

    Full Text Available The products of oxidative stress trigger chronic low-grade inflammation (pathophysiological parainflammation process in AMD patients. In early AMD, soft drusen contain many mediators of chronic low-grade inflammation such as C-reactive protein, adducts of the carboxyethylpyrrole protein, immunoglobulins, and acute phase molecules, as well as the complement-related proteins C3a, C5a, C5, C5b-9, CFH, CD35, and CD46. The complement system, mainly alternative pathway, mediates chronic autologous pathophysiological parainflammation in dry and exudative AMD, especially in the Y402H gene polymorphism, which causes hypofunction/lack of the protective complement factor H (CFH and facilitates chronic inflammation mediated by C-reactive protein (CRP. Microglial activation induces photoreceptor cells injury and leads to the development of dry AMD. Many autoantibodies (antibodies against alpha beta crystallin, alpha-actinin, amyloid, C1q, chondroitin, collagen I, collagen III, collagen IV, elastin, fibronectin, heparan sulfate, histone H2A, histone H2B, hyaluronic acid, laminin, proteoglycan, vimentin, vitronectin, and aldolase C and pyruvate kinase M2 and overexpression of Fcc receptors play role in immune-mediated inflammation in AMD patients and in animal model. Macrophages infiltration of retinal/choroidal interface acts as protective factor in early AMD (M2 phenotype macrophages; however it acts as proinflammatory and proangiogenic factor in advanced AMD (M1 and M2 phenotype macrophages.

  12. Pulmonary hypertension in chronic obstructive and interstitial lung diseases

    DEFF Research Database (Denmark)

    Andersen, Charlotte U; Mellemkjær, Søren; Nielsen-Kudsk, Jens Erik;

    2013-01-01

    treatment with existent drugs effective in pulmonary arterial hypertension (PAH) is beneficial in lung disease related PH. Studies investigating existing PAH drugs in animal models of lung disease related PH have indicated a positive effect, and so have case reports and open label studies. However......, and is considered one of the most frequent types of PH. However, the prevalence of PH among patients with COPD and ILD is not clear. The diagnosis of PH in chronic lung disease is often established by echocardiographic screening, but definitive diagnosis requires right heart catheterization, which...... is not systematically performed in clinical practice. Given the large number of patients with chronic lung disease, biomarkers to preclude or increase suspicion of PH are needed. NT-proBNP may be used as a rule-out test, but biomarkers with a high specificity for PH are still required. It is not known whether specific...

  13. Group 2 innate lymphoid cells in lung inflammation

    NARCIS (Netherlands)

    B.W.S. Li (Bobby W.); R.W. Hendriks (Rudi)

    2013-01-01

    textabstractSummary: Although allergic asthma is a heterogeneous disease, allergen-specific T helper 2 (Th2) cells producing the key cytokines involved in type 2 inflammation, interleukin-4 (IL-4), IL-5 and IL-13, are thought to play a major role in asthma pathogenesis. This model is challenged by t

  14. The Prevalence of Oral Inflammation Among Denture Wearing Patients with Chronic Obstructive Pulmonary Disease.

    Science.gov (United States)

    Przybyłowska, D; Rubinsztajn, R; Chazan, R; Swoboda-Kopeć, E; Kostrzewa-Janicka, J; Mierzwińska-Nastalska, E

    2015-01-01

    Oral inflammation is an important contributor to the etiology of chronic obstructive pulmonary disease, which can impact patient's health status. Previous studies indicate that people with poor oral health are at higher risk for nosocomial pneumonia. Denture wearing is one promoting factor in the development of mucosal infections. Colonization of the denture plaque by Gram-negative bacteria, Candida spp., or other respiratory pathogens, occurring locally, may be aspirated to the lungs. The studies showed that chronic obstructive pulmonary disease (COPD) patients treated with combinations of medicines with corticosteroids more frequently suffer from Candida-associated denture stomatitis. Treatment of oral candidiasis in patients with COPD constitutes a therapeutic problem. Therefore, it is essential to pay attention to the condition of oral mucosal membrane and denture hygiene habits. The guidelines for care and maintenance of dentures for COPD patients are presented in this paper. The majority of patients required improvement of their prosthetic and oral hygiene. Standard oral hygiene procedures in relation to dentures, conducted for prophylaxis of stomatitis complicated by mucosal infection among immunocompromised patients, are essential to maintain healthy oral tissues. The elimination of traumatic denture action in dental office, compliance with oral and denture hygiene, proper use and storage of prosthetic appliances in a dry environment outside the oral cavity can reduce susceptibility to infection. Proper attention to hygiene, including brushing and rinsing the mouth, may also help prevent denture stomatitis in these patients.

  15. Human mesenchymal stem cells suppress chronic airway inflammation in the murine ovalbumin asthma model.

    Science.gov (United States)

    Bonfield, Tracey L; Koloze, Mary; Lennon, Donald P; Zuchowski, Brandon; Yang, Sung Eun; Caplan, Arnold I

    2010-12-01

    Allogeneic human mesenchymal stem cells (hMSCs) introduced intravenously can have profound anti-inflammatory activity resulting in suppression of graft vs. host disease as well as regenerative events in the case of stroke, infarct, spinal cord injury, meniscus regeneration, tendinitis, acute renal failure, and heart disease in human and animal models of these diseases. hMSCs produce bioactive factors that provide molecular cuing for: 1) immunosuppression of T cells; 2) antiscarring; 3) angiogenesis; 4) antiapoptosis; and 5) regeneration (i.e., mitotic for host-derived progenitor cells). Studies have shown that hMSCs have profound effects on the immune system and are well-tolerated and therapeutically active in immunocompetent rodent models of multiple sclerosis and stroke. Furthermore, intravenous administration of MSCs results in pulmonary localization. Asthma is a major debilitating pulmonary disease that impacts in excess of 150 million people in the world with uncontrolled asthma potentially leading to death. In addition, the socioeconomic impact of asthma-associated illnesses at the pediatric and adult level are in the millions of dollars in healthcare costs and lost days of work. hMSCs may provide a viable multiaction therapeutic for this inflammatory lung disease by secreting bioactive factors or directing cellular activity. Our studies show the effectiveness and specificity of the hMSCs on decreasing chronic airway inflammation associated with the murine ovalbumin model of asthma. In addition, the results from these studies verify the in vivo immunoeffectiveness of hMSCs in rodents and support the potential therapeutic use of hMSCs for the treatment of airway inflammation associated with chronic asthma. PMID:20817776

  16. Endogenous lipid mediators in the resolution of airway inflammation

    OpenAIRE

    Haworth, O.; Levy, B D

    2007-01-01

    Acute inflammation in the lung is fundamentally important to host defence, but chronic or excessive inflammation leads to several common respiratory diseases, including asthma and acute respiratory distress syndrome.

  17. Spred-2 deficiency exacerbates lipopolysaccharide-induced acute lung inflammation in mice.

    Directory of Open Access Journals (Sweden)

    Yang Xu

    Full Text Available BACKGROUND: Acute respiratory distress syndrome (ARDS is a severe and life-threatening acute lung injury (ALI that is caused by noxious stimuli and pathogens. ALI is characterized by marked acute inflammation with elevated alveolar cytokine levels. Mitogen-activated protein kinase (MAPK pathways are involved in cytokine production, but the mechanisms that regulate these pathways remain poorly characterized. Here, we focused on the role of Sprouty-related EVH1-domain-containing protein (Spred-2, a negative regulator of the Ras-Raf-extracellular signal-regulated kinase (ERK-MAPK pathway, in lipopolysaccharide (LPS-induced acute lung inflammation. METHODS: Wild-type (WT mice and Spred-2(-/- mice were exposed to intratracheal LPS (50 µg in 50 µL PBS to induce pulmonary inflammation. After LPS-injection, the lungs were harvested to assess leukocyte infiltration, cytokine and chemokine production, ERK-MAPK activation and immunopathology. For ex vivo experiments, alveolar macrophages were harvested from untreated WT and Spred-2(-/- mice and stimulated with LPS. In in vitro experiments, specific knock down of Spred-2 by siRNA or overexpression of Spred-2 by transfection with a plasmid encoding the Spred-2 sense sequence was introduced into murine RAW264.7 macrophage cells or MLE-12 lung epithelial cells. RESULTS: LPS-induced acute lung inflammation was significantly exacerbated in Spred-2(-/- mice compared with WT mice, as indicated by the numbers of infiltrating leukocytes, levels of alveolar TNF-α, CXCL2 and CCL2 in a later phase, and lung pathology. U0126, a selective MEK/ERK inhibitor, reduced the augmented LPS-induced inflammation in Spred-2(-/- mice. Specific knock down of Spred-2 augmented LPS-induced cytokine and chemokine responses in RAW264.7 cells and MLE-12 cells, whereas Spred-2 overexpression decreased this response in RAW264.7 cells. CONCLUSIONS: The ERK-MAPK pathway is involved in LPS-induced acute lung inflammation. Spred-2 controls

  18. Induction of vascular remodeling in the lung by chronic house dust mite exposure.

    Science.gov (United States)

    Rydell-Törmänen, Kristina; Johnson, Jill R; Fattouh, Ramzi; Jordana, Manel; Erjefält, Jonas S

    2008-07-01

    Structural changes to the lung are associated with chronic asthma. In addition to alterations to the airway wall, asthma is associated with vascular modifications, although this aspect of remodeling is poorly understood. We sought to evaluate the character and kinetics of vascular remodeling in response to chronic aeroallergen exposure. Because many ovalbumin-driven models used to investigate allergic airway disease do so in the absence of persistent airway inflammation, we used a protocol of chronic respiratory exposure to house dust mite extract (HDME), which has been shown to induce persistent airway inflammation consistent with that seen in humans with asthma. Mice were exposed to HDME intranasally for 7 or 20 consecutive weeks, and resolution of the inflammatory and remodeling response to allergen was investigated 4 weeks after the end of a 7-week exposure protocol. Measures of vascular remodeling, including total collagen deposition, procollagen I production, endothelial and smooth muscle cell proliferation, smooth muscle area, and presence of myofibroblasts, were investigated histologically in lung vessels of different sizes and locations. We observed an increase in total collagen content, which did not resolve upon cessation of allergen exposure. Other parameters were significantly increased after 7 and/or 20 weeks of allergen exposure but returned to baseline after allergen withdrawal. We conclude that respiratory HDME exposure induces airway remodeling and pulmonary vascular remodeling, and, in accordance with airway remodeling, some components of these structural changes may be irreversible. PMID:18314535

  19. Pulmonary hypertension in chronic interstitial lung diseases

    OpenAIRE

    Antonella Caminati; Roberto Cassandro; Sergio Harari

    2013-01-01

    Pulmonary hypertension (PH) is a common complication of interstitial lung diseases (ILDs), particularly in idiopathic pulmonary fibrosis and ILD associated with connective tissue disease. However, other lung diseases, such as combined pulmonary fibrosis and emphysema syndrome, pulmonary Langerhans cell histiocytosis, and lymphangioleiomyomatosis, may also include PH in their clinical manifestations. In all of these diseases, PH is associated with reduced exercise capacity and poor prognosis. ...

  20. Inhibition of Pyk2 blocks lung inflammation and injury in a mouse model of acute lung injury

    Directory of Open Access Journals (Sweden)

    Duan Yingli

    2012-01-01

    Full Text Available Abstract Background Proline-rich tyrosine kinase 2 (Pyk2 is essential in neutrophil degranulation and chemotaxis in vitro. However, its effect on the process of lung inflammation and edema formation during LPS induced acute lung injury (ALI remains unknown. The goal of the present study was to determine the effect of inhibiting Pyk2 on LPS-induced acute lung inflammation and injury in vivo. Methods C57BL6 mice were given either 10 mg/kg LPS or saline intratracheally. Inhibition of Pyk2 was effected by intraperitoneal administration TAT-Pyk2-CT 1 h before challenge. Bronchoalveolar lavage analysis of cell counts, lung histology and protein concentration in BAL were analyzed at 18 h after LPS treatment. KC and MIP-2 concentrations in BAL were measured by a mouse cytokine multiplex kit. The static lung compliance was determined by pressure-volume curve using a computer-controlled small animal ventilator. The extravasated Evans blue concentration in lung homogenate was determined spectrophotometrically. Results Intratracheal instillation of LPS induced significant neutrophil infiltration into the lung interstitium and alveolar space, which was attenuated by pre-treatment with TAT-Pyk2-CT. TAT-Pyk2-CT pretreatment also attenuated 1 myeloperoxidase content in lung tissues, 2 vascular leakage as measured by Evans blue dye extravasation in the lungs and the increase in protein concentration in bronchoalveolar lavage, and 3 the decrease in lung compliance. In each paradigm, treatment with control protein TAT-GFP had no blocking effect. By contrast, production of neutrophil chemokines MIP-2 and keratinocyte-derived chemokine in the bronchoalveolar lavage was not reduced by TAT-Pyk2-CT. Western blot analysis confirmed that tyrosine phosphorylation of Pyk2 in LPS-challenged lungs was reduced to control levels by TAT-Pyk2-CT pretreatment. Conclusions These results suggest that Pyk2 plays an important role in the development of acute lung injury in mice and

  1. Effects of budesonide and N-acetylcysteine on acute lung hyperinflation, inflammation and injury in rats.

    Science.gov (United States)

    Jansson, Anne-Helene; Eriksson, Christina; Wang, Xiangdong

    2005-08-01

    Leukocyte activation and production of inflammatory mediators and reactive oxygen species are important in the pathogenesis of lipopolysaccharide (LPS)-induced acute lung injury. The present study investigated acute lung hyperinflation, edema, and lung inflammation 4 h after an intratracheal instillation of LPS (0.5, 2.5, 5, 10, 50, 100, 500, 1000, and 5000 microg/ml/kg). Effects of budesonide, an inhaled anti-inflammatory corticosteroids, and N-acetylcysteine (NAC), an antioxidant, were evaluated in Wistar rats receiving either low (2.5 microg/ml/kg) or high (50 microg/ml/kg) concentrations of LPS. This study demonstrates that LPS in a concentration-dependent pattern induces acute lung hyperinflation measured by excised lung gas volume (25-45% above control), lung injury indicated by increased lung weight (10-60%), and lung inflammation characterized by the infiltration of leukocytes (40-14000%) and neutrophils (80-17000%) and the production of cytokines (up to 2700%) and chemokines (up to 350%) in bronchoalveolar lavage fluid (BALF). Pretreatment with NAC partially prevented tumor necrosis factor alpha (TNFalpha) production induced by the low concentration of LPS, while pretreatment with budesonide totally prevented the increased production of TNFalpha, interleukin (IL)-1beta, IL-6, and monocyte chemoattractive protein (MCP)-1 after LPS challenge at both low and high concentrations. Budesonide failed to prevent BALF levels of macrophage inflammatory protein (MIP)-2 and cytokine-induced neutrophil chemoattractant 1 (GRO/CINC-1) as well as lung hyperinflation induced by both low and high concentrations of LPS. Pretreatment with budesonide totally prevented the formation of lung edema at the low concentration of LPS and had partial effects on acute lung injury and leukocyte influx at the high concentrations. Thus, our data indicate that therapeutic effects of budesonide and NAC are dependent upon the severity of the disease.

  2. [Therapeutic training and sports in chronic diseases of the lung].

    Science.gov (United States)

    Podolsky, A; Haber, P

    1993-01-01

    Training is defined as systematic physical activity in order to improve the physical working capacity, which causes measurable morphological and functional changes in organs. Effects and the rules of applying aerobic endurance training in patients with chronic diseases of the lungs are dealt with. Training does not replace the normal medication, but is an additional therapeutic mean in order to regain physical working capacity, lost by chronic immobilization in the natural course of disease. Contraindications are acute diseases and exacerbations, but not a certain degree of the disease. Training does not improve the lung function, but the function of the other organs, the physical working capacity ist based on (circulation, musculature). This helps to use optimally the remaining reserves of lung function. Methods of aerobic endurance training are described, the definition of aims, performance diagnostic and the finding of the exact doses of training according to intensity, duration, frequency and the weekly netto training time. The training in different diseases of the lungs is discussed: In asthma bronchiale the prophylaxis of the exercise induced asthma and permitted and forbidden drugs for asthmatics according to the rules of international olympic committee. In chronic bronchitis with arterial hypoxemia, in restrictive lung diseases and in pulmonary hypertension. At last the way to prescribing training for patients with chronic pulmonary diseases is described as well as the advising of patients wishing to do sport by their own motivation or planning projects, for instance touristic ones, which require physical stress. PMID:8465532

  3. Comparison of lung alveolar and tissue cells in silica-induced inflammation.

    Science.gov (United States)

    Sjöstrand, M; Absher, P M; Hemenway, D R; Trombley, L; Baldor, L C

    1991-01-01

    The silicon dioxide mineral, cristobalite (CRS) induces inflammation involving both alveolar cells and connective tissue compartments. In this study, we compared lung cells recovered by whole lung lavage and by digestion of lung tissue from rats at varying times after 8 days of exposure to aerosolized CRS. Control and exposed rats were examined between 2 and 36 wk after exposure. Lavaged cells were obtained by bronchoalveolar lavage with phosphate-buffered saline. Lung wall cells were prepared via collagenase digestion of lung tissue slices. Cells from lavage and lung wall were separated by Percoll density centrifugation. The three upper fractions, containing mostly macrophages, were cultured, and the conditioned medium was assayed for effect on lung fibroblast growth and for activity of the lysosomal enzyme, N-acetyl-beta-D-glucosaminidase. Results demonstrated that the cells separated from the lung walls exhibited different reaction patterns compared with those cells recovered by lavage. The lung wall cells exhibited a progressive increase in the number of macrophages and lymphocytes compared with a steady state in cells of the lung lavage. This increase in macrophages apparently was due to low density cells, which showed features of silica exposure. Secretion of a fibroblast-stimulating factor was consistently high by lung wall macrophages, whereas lung lavage macrophages showed inconsistent variations. The secretion of NAG was increased in lung lavage macrophages, but decreased at most observation times in lung wall macrophages. No differences were found among cells in the different density fractions regarding fibroblast stimulation and enzyme secretion.(ABSTRACT TRUNCATED AT 250 WORDS)

  4. Lung Neutrophilia in Myeloperoxidase Deficient Mice during the Course of Acute Pulmonary Inflammation

    Directory of Open Access Journals (Sweden)

    Silvie Kremserova

    2016-01-01

    Full Text Available Systemic inflammation accompanying diseases such as sepsis affects primarily lungs and induces their failure. This remains the most common cause of sepsis induced mortality. While neutrophils play a key role in pulmonary failure, the mechanisms remain incompletely characterized. We report that myeloperoxidase (MPO, abundant enzyme in neutrophil granules, modulates the course of acute pulmonary inflammatory responses induced by intranasal application of lipopolysaccharide. MPO deficient mice had significantly increased numbers of airway infiltrated neutrophils compared to wild-type mice during the whole course of lung inflammation. This was accompanied by higher levels of RANTES in bronchoalveolar lavage fluid from the MPO deficient mice. Other markers of lung injury and inflammation, which contribute to recruitment of neutrophils into the inflamed lungs, including total protein and other selected proinflammatory cytokines did not significantly differ in bronchoalveolar lavage fluid from the wild-type and the MPO deficient mice. Interestingly, MPO deficient neutrophils revealed a decreased rate of cell death characterized by phosphatidylserine surface expression. Collectively, the importance of MPO in regulation of pulmonary inflammation, independent of its putative microbicidal functions, can be potentially linked to MPO ability to modulate the life span of neutrophils and to affect accumulation of chemotactic factors at the inflammatory site.

  5. Lung Neutrophilia in Myeloperoxidase Deficient Mice during the Course of Acute Pulmonary Inflammation.

    Science.gov (United States)

    Kremserova, Silvie; Perecko, Tomas; Soucek, Karel; Klinke, Anna; Baldus, Stephan; Eiserich, Jason P; Kubala, Lukas

    2016-01-01

    Systemic inflammation accompanying diseases such as sepsis affects primarily lungs and induces their failure. This remains the most common cause of sepsis induced mortality. While neutrophils play a key role in pulmonary failure, the mechanisms remain incompletely characterized. We report that myeloperoxidase (MPO), abundant enzyme in neutrophil granules, modulates the course of acute pulmonary inflammatory responses induced by intranasal application of lipopolysaccharide. MPO deficient mice had significantly increased numbers of airway infiltrated neutrophils compared to wild-type mice during the whole course of lung inflammation. This was accompanied by higher levels of RANTES in bronchoalveolar lavage fluid from the MPO deficient mice. Other markers of lung injury and inflammation, which contribute to recruitment of neutrophils into the inflamed lungs, including total protein and other selected proinflammatory cytokines did not significantly differ in bronchoalveolar lavage fluid from the wild-type and the MPO deficient mice. Interestingly, MPO deficient neutrophils revealed a decreased rate of cell death characterized by phosphatidylserine surface expression. Collectively, the importance of MPO in regulation of pulmonary inflammation, independent of its putative microbicidal functions, can be potentially linked to MPO ability to modulate the life span of neutrophils and to affect accumulation of chemotactic factors at the inflammatory site. PMID:26998194

  6. Inhibition of Phosphodiesterase-4 during Pneumococcal Pneumonia Reduces Inflammation and Lung Injury in Mice.

    Science.gov (United States)

    Tavares, Luciana P; Garcia, Cristiana C; Vago, Juliana P; Queiroz-Junior, Celso M; Galvão, Izabela; David, Bruna A; Rachid, Milene A; Silva, Patrícia M R; Russo, Remo C; Teixeira, Mauro M; Sousa, Lirlândia P

    2016-07-01

    Pneumococcal pneumonia is a leading cause of mortality worldwide. The inflammatory response to bacteria is necessary to control infection, but it may also contribute to tissue damage. Phosphodiesterase-4 inhibitors, such as rolipram (ROL), effectively reduce inflammation. Here, we examined the impact of ROL in a pneumococcal pneumonia murine model. Mice were infected intranasally with 10(5)-10(6) CFU of Streptococcus pneumoniae, treated with ROL in a prophylactic or therapeutic schedule in combination, or not, with the antibiotic ceftriaxone. Inflammation and bacteria counts were assessed, and ex vivo phagocytosis assays were performed. ROL treatment during S. pneumoniae infection decreased neutrophil recruitment into lungs and airways and reduced lung injury. Prophylactic ROL treatment also decreased cytokine levels in the airways. Although modulation of inflammation by ROL ameliorated pneumonia, bacteria burden was not reduced. On the other hand, antibiotic therapy reduced bacteria without reducing neutrophil infiltration, cytokine level, or lung injury. Combined ROL and ceftriaxone treatment decreased lethality rates and was more efficient in reducing inflammation, by increasing proresolving protein annexin A1 (AnxA1) expression, and bacterial burden by enhancing phagocytosis. Lack of AnxA1 increased inflammation and lethality induced by pneumococcal infection. These data show that immunomodulatory effects of phosphodiesterase-4 inhibitors are useful during severe pneumococcal pneumonia and suggest their potential benefit as adjunctive therapy during infectious diseases. PMID:26677751

  7. Collagenolytic Matrix Metalloproteinases in Chronic Obstructive Lung Disease and Cancer

    International Nuclear Information System (INIS)

    Chronic obstructive pulmonary disease (COPD) and lung cancer result in significant morbidity and mortality worldwide. In addition to the role of environmental smoke exposure in the development of both diseases, recent epidemiological studies suggests a connection between the development of COPD and lung cancer. Furthermore, individuals with concomitant COPD and cancer have a poor prognosis when compared with individuals with lung cancer alone. The modulation of molecular pathways activated during emphysema likely lead to an increased susceptibility to lung tumor growth and metastasis. This review summarizes what is known in the literature examining the molecular pathways affecting matrix metalloproteinases (MMPs) in this process as well as external factors such as smoke exposure that have an impact on tumor growth and metastasis. Increased expression of MMPs provides a unifying link between lung cancer and COPD

  8. Collagenolytic Matrix Metalloproteinases in Chronic Obstructive Lung Disease and Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Woode, Denzel; Shiomi, Takayuki; D’Armiento, Jeanine, E-mail: jmd12@cumc.columbia.edu [Department of Anesthesiology, Columbia University, College of Physicians and Surgeons, New York, NY 10033 (United States)

    2015-02-05

    Chronic obstructive pulmonary disease (COPD) and lung cancer result in significant morbidity and mortality worldwide. In addition to the role of environmental smoke exposure in the development of both diseases, recent epidemiological studies suggests a connection between the development of COPD and lung cancer. Furthermore, individuals with concomitant COPD and cancer have a poor prognosis when compared with individuals with lung cancer alone. The modulation of molecular pathways activated during emphysema likely lead to an increased susceptibility to lung tumor growth and metastasis. This review summarizes what is known in the literature examining the molecular pathways affecting matrix metalloproteinases (MMPs) in this process as well as external factors such as smoke exposure that have an impact on tumor growth and metastasis. Increased expression of MMPs provides a unifying link between lung cancer and COPD.

  9. Collagenolytic Matrix Metalloproteinases in Chronic Obstructive Lung Disease and Cancer

    Directory of Open Access Journals (Sweden)

    Denzel Woode

    2015-02-01

    Full Text Available Chronic obstructive pulmonary disease (COPD and lung cancer result in significant morbidity and mortality worldwide. In addition to the role of environmental smoke exposure in the development of both diseases, recent epidemiological studies suggests a connection between the development of COPD and lung cancer. Furthermore, individuals with concomitant COPD and cancer have a poor prognosis when compared with individuals with lung cancer alone. The modulation of molecular pathways activated during emphysema likely lead to an increased susceptibility to lung tumor growth and metastasis. This review summarizes what is known in the literature examining the molecular pathways affecting matrix metalloproteinases (MMPs in this process as well as external factors such as smoke exposure that have an impact on tumor growth and metastasis. Increased expression of MMPs provides a unifying link between lung cancer and COPD.

  10. Patient-Specific Airway Wall Remodeling in Chronic Lung Disease.

    Science.gov (United States)

    Eskandari, Mona; Kuschner, Ware G; Kuhl, Ellen

    2015-10-01

    Chronic lung disease affects more than a quarter of the adult population; yet, the mechanics of the airways are poorly understood. The pathophysiology of chronic lung disease is commonly characterized by mucosal growth and smooth muscle contraction of the airways, which initiate an inward folding of the mucosal layer and progressive airflow obstruction. Since the degree of obstruction is closely correlated with the number of folds, mucosal folding has been extensively studied in idealized circular cross sections. However, airflow obstruction has never been studied in real airway geometries; the behavior of imperfect, non-cylindrical, continuously branching airways remains unknown. Here we model the effects of chronic lung disease using the nonlinear field theories of mechanics supplemented by the theory of finite growth. We perform finite element analysis of patient-specific Y-branch segments created from magnetic resonance images. We demonstrate that the mucosal folding pattern is insensitive to the specific airway geometry, but that it critically depends on the mucosal and submucosal stiffness, thickness, and loading mechanism. Our results suggests that patient-specific airway models with inherent geometric imperfections are more sensitive to obstruction than idealized circular models. Our models help to explain the pathophysiology of airway obstruction in chronic lung disease and hold promise to improve the diagnostics and treatment of asthma, bronchitis, chronic obstructive pulmonary disease, and respiratory failure. PMID:25821112

  11. Ab interno laser sclerostomy in aphakic patients with glaucoma and chronic inflammation.

    Science.gov (United States)

    Wilson, R P; Javitt, J C

    1990-08-15

    Five patients with aphakia, glaucoma, and chronic inflammation were treated with ab interno sclerostomy by using the continuous wave Nd:YAG laser focused through a sapphire probe. After a follow-up period of 24 to 28 months, three of five patients had good intraocular pressure control. The sclerostomy failed in one patient when it was occluded by vitreous. The second failure was attributed to closure of the sclerostomy because of chronic intraocular inflammation.

  12. The Relationship Between Chronic Inflammation and Glucidic-Lipidic Profile Disorders in Kidney Transplant Recipients

    OpenAIRE

    Tarța I.D.; Căldăraru Carmen Denise; Gliga Mirela; Huțanu Adina; Bajko Z; Carașca E; Dogaru G.A.

    2016-01-01

    Introduction: Chronic inflammation has a proven role in atherogenesis, lipid profile parameters being related to cytokine production. In kidney transplant recipients, interleukin 6 (IL-6) is significantly associated with graft-related outcomes and also alterations of cholesterol and triglyceride metabolism. The aim of this study was to investigate the relationship between chronic inflammation and glucidic-lipidic metabolism disorders in a group of patients with kidney transplantation as renal...

  13. miR-155 promotes T follicular helper cell accumulation during chronic, low-grade inflammation.

    OpenAIRE

    Hu, Ruozhen; Kagele, Dominique A; Huffaker, Thomas B; Runtsch, Marah C; Alexander, Margaret; Liu, Jin; Bake, Erin; Su, Wei; Williams, Matthew A.; Rao, Dinesh S.; Möller, Thomas; Garden, Gwenn A; Round, June L.; O’Connell, Ryan M.

    2014-01-01

    Chronic inflammation is a contributing factor to most life shortening human diseases. However, the molecular and cellular mechanisms that sustain chronic inflammatory responses remain poorly understood making it difficult to treat this deleterious condition. Using a mouse model of age-dependent inflammation that results from a deficiency in miR-146a, we demonstrate that miR-155 contributed to the progressive inflammatory disease that emerged as Mir146a−/− mice grew older. Upon analyzing lymph...

  14. Chronic Exposure to Water-Pipe Smoke Induces Alveolar Enlargement, DNA Damage and Impairment of Lung Function

    Directory of Open Access Journals (Sweden)

    Abderrahim Nemmar

    2016-03-01

    Full Text Available Background/Aim: Epidemiological evidence indicates that water-pipe smoking (WPS adversely affects the respiratory system. However, the mechanisms underlying its effects are not well understood. Recent experimental studies reported the occurrence of lung inflammation and oxidative stress following acute and subacute exposure to WPS. Here, we wanted to verify the extent of inflammation and oxidative stress in mice chronically-exposed to WPS and to evaluate, for the first time, its effect on alveolar injury and DNA damage and their association with impairment of lung function. Methods: Mice were nose-only exposed to mainstream WPS (30 min/day; 5 days/week for 6 consecutive months. Control mice were exposed using the same protocol to atmospheric air only. At the end of the exposure period, several respiratory parameters were assessed. Results: In bronchoalveolar lavage fluid, WPS increased neutrophil and lymphocyte numbers, lactate dehydrogenase, myeloperoxidase and matrix metallopeptidase 9 activities, as well as several proinflammatory cytokines. In lung tissue, lipid peroxidation, reactive oxygen species, superoxide dismutase activity and reduced glutathione were all increased by WPS exposure. Along with oxidative stress, WPS exposure significantly increased lung DNA damage index. Histologically the lungs of WPS-exposed mice had foci of mixed inflammatory cells infiltration in the interalveolar interstitium which consisted of neutrophils, lymphocytes and macrophages. Interestingly, we found dilated alveolar spaces and alveolar ducts with damaged interalveolar septae, and impairment of lung function following WPS exposure. Conclusion: We show the persistence of lung inflammation and oxidative stress in mice chronically-exposed to WPS and demonstrate, for the first time, the occurrence of DNA damage and enlargement of alveolar spaces and ducts associated with impairment of lung function. Our findings provide novel mechanistic elucidation for the

  15. Aryl Hydrocarbon Receptor Protects Lungs from Cockroach Allergen-Induced Inflammation by Modulating Mesenchymal Stem Cells.

    Science.gov (United States)

    Xu, Ting; Zhou, Yufeng; Qiu, Lipeng; Do, Danh C; Zhao, Yilin; Cui, Zhuang; Wang, Heng; Liu, Xiaopeng; Saradna, Arjun; Cao, Xu; Wan, Mei; Gao, Peisong

    2015-12-15

    Exposure to cockroach allergen leads to allergic sensitization and increased risk of developing asthma. Aryl hydrocarbon receptor (AhR), a receptor for many common environmental contaminants, can sense not only environmental pollutants but also microbial insults. Mesenchymal stem cells (MSCs) are multipotent progenitor cells with the capacity to modulate immune responses. In this study, we investigated whether AhR can sense cockroach allergens and modulate allergen-induced lung inflammation through MSCs. We found that cockroach allergen-treated AhR-deficient (AhR(-/-)) mice showed exacerbation of lung inflammation when compared with wild-type (WT) mice. In contrast, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), an AhR agonist, significantly suppressed allergen-induced mouse lung inflammation. MSCs were significantly reduced in cockroach allergen-challenged AhR(-/-) mice as compared with WT mice, but increased in cockroach allergen-challenged WT mice when treated with TCDD. Moreover, MSCs express AhR, and AhR signaling can be activated by cockroach allergen with increased expression of its downstream genes cyp1a1 and cyp1b1. Furthermore, we tracked the migration of i.v.-injected GFP(+) MSCs and found that cockroach allergen-challenged AhR(-/-) mice displayed less migration of MSCs to the lungs compared with WT. The AhR-mediated MSC migration was further verified by an in vitro Transwell migration assay. Epithelial conditioned medium prepared from cockroach extract-challenged epithelial cells significantly induced MSC migration, which was further enhanced by TCDD. The administration of MSCs significantly attenuated cockroach allergen-induced inflammation, which was abolished by TGF-β1-neutralizing Ab. These results suggest that AhR plays an important role in protecting lungs from allergen-induced inflammation by modulating MSC recruitment and their immune-suppressive activity. PMID:26561548

  16. Sildenafil attenuates pulmonary inflammation and fibrin deposition, mortality and right ventricular hypertrophy in neonatal hyperoxic lung injury

    Directory of Open Access Journals (Sweden)

    Boersma Hester

    2009-04-01

    Full Text Available Abstract Background Phosphodiesterase-5 inhibition with sildenafil has been used to treat severe pulmonary hypertension and bronchopulmonary dysplasia (BPD, a chronic lung disease in very preterm infants who were mechanically ventilated for respiratory distress syndrome. Methods Sildenafil treatment was investigated in 2 models of experimental BPD: a lethal neonatal model, in which rat pups were continuously exposed to hyperoxia and treated daily with sildenafil (50–150 mg/kg body weight/day; injected subcutaneously and a neonatal lung injury-recovery model in which rat pups were exposed to hyperoxia for 9 days, followed by 9 days of recovery in room air and started sildenafil treatment on day 6 of hyperoxia exposure. Parameters investigated include survival, histopathology, fibrin deposition, alveolar vascular leakage, right ventricular hypertrophy, and differential mRNA expression in lung and heart tissue. Results Prophylactic treatment with an optimal dose of sildenafil (2 × 50 mg/kg/day significantly increased lung cGMP levels, prolonged median survival, reduced fibrin deposition, total protein content in bronchoalveolar lavage fluid, inflammation and septum thickness. Treatment with sildenafil partially corrected the differential mRNA expression of amphiregulin, plasminogen activator inhibitor-1, fibroblast growth factor receptor-4 and vascular endothelial growth factor receptor-2 in the lung and of brain and c-type natriuretic peptides and the natriuretic peptide receptors NPR-A, -B, and -C in the right ventricle. In the lethal and injury-recovery model we demonstrated improved alveolarization and angiogenesis by attenuating mean linear intercept and arteriolar wall thickness and increasing pulmonary blood vessel density, and right ventricular hypertrophy (RVH. Conclusion Sildenafil treatment, started simultaneously with exposure to hyperoxia after birth, prolongs survival, increases pulmonary cGMP levels, reduces the pulmonary

  17. Prior Lung Inflammation Impacts on Body Distribution of Gold Nanoparticles

    Directory of Open Access Journals (Sweden)

    Salik Hussain

    2013-01-01

    Full Text Available Introduction. Gold- (Au- based nanomaterials have shown promising potential in nanomedicine. The individual health status is an important determinant of the response to injury/exposure. It is, therefore, critical to evaluate exposure to Au-nanomaterials with varied preexisting health status. Objective. The goal of this research was to determine the extent of extrapulmonary translocation from healthy and inflamed lungs after pulmonary exposure to AuNPs. Male BALB/c mice received a single dose of 0.8 mg·kg−1 AuNPs (40 nm by oropharyngeal aspiration 24 hours after priming with LPS (0.4 mg·kg−1 through the same route. Metal contents were analyzed in different organs by inductively coupled plasma-mass spectrometry (ICP-MS. Results. Oropharyngeal aspiration resulted in high metal concentrations in lungs (P<0.001; however, these were much lower after pretreatment with LPS (P<0.05. Significantly higher concentrations of Au were detected in heart and thymus of healthy animals, whereas higher concentrations of Au NPs were observed in spleen in LPS-primed animals. Conclusions. The distribution of AuNPs from lungs to secondary target organs depends upon the health status, indicating that targeting of distinct secondary organs in nanomedicine needs to be considered carefully under health and inflammatory conditions.

  18. Prior Lung Inflammation Impacts on Body Distribution of Gold Nanoparticles

    Science.gov (United States)

    Hussain, Salik; Vanoirbeek, Jeroen A. J.; Haenen, Steven; Haufroid, Vincent; Boland, Sonja; Marano, Francelyne; Nemery, Benoit; Hoet, Peter H. M.

    2013-01-01

    Introduction. Gold- (Au-) based nanomaterials have shown promising potential in nanomedicine. The individual health status is an important determinant of the response to injury/exposure. It is, therefore, critical to evaluate exposure to Au-nanomaterials with varied preexisting health status. Objective. The goal of this research was to determine the extent of extrapulmonary translocation from healthy and inflamed lungs after pulmonary exposure to AuNPs. Male BALB/c mice received a single dose of 0.8 mg · kg−1 AuNPs (40 nm) by oropharyngeal aspiration 24 hours after priming with LPS (0.4 mg · kg−1) through the same route. Metal contents were analyzed in different organs by inductively coupled plasma-mass spectrometry (ICP-MS). Results. Oropharyngeal aspiration resulted in high metal concentrations in lungs (P < 0.001); however, these were much lower after pretreatment with LPS (P < 0.05). Significantly higher concentrations of Au were detected in heart and thymus of healthy animals, whereas higher concentrations of Au NPs were observed in spleen in LPS-primed animals. Conclusions. The distribution of AuNPs from lungs to secondary target organs depends upon the health status, indicating that targeting of distinct secondary organs in nanomedicine needs to be considered carefully under health and inflammatory conditions. PMID:23509805

  19. Effects of exercise training on chronic inflammation in obesity : current evidence and potential mechanisms.

    Science.gov (United States)

    You, Tongjian; Arsenis, Nicole C; Disanzo, Beth L; Lamonte, Michael J

    2013-04-01

    Chronic, systemic inflammation is an independent risk factor for several major clinical diseases. In obesity, circulating levels of inflammatory markers are elevated, possibly due to increased production of pro-inflammatory cytokines from several tissues/cells, including macrophages within adipose tissue, vascular endothelial cells and peripheral blood mononuclear cells. Recent evidence supports that adipose tissue hypoxia may be an important mechanism through which enlarged adipose tissue elicits local tissue inflammation and further contributes to systemic inflammation. Current evidence supports that exercise training, such as aerobic and resistance exercise, reduces chronic inflammation, especially in obese individuals with high levels of inflammatory biomarkers undergoing a longer-term intervention. Several studies have reported that this effect is independent of the exercise-induced weight loss. There are several mechanisms through which exercise training reduces chronic inflammation, including its effect on muscle tissue to generate muscle-derived, anti-inflammatory 'myokine', its effect on adipose tissue to improve hypoxia and reduce local adipose tissue inflammation, its effect on endothelial cells to reduce leukocyte adhesion and cytokine production systemically, and its effect on the immune system to lower the number of pro-inflammatory cells and reduce pro-inflammatory cytokine production per cell. Of these potential mechanisms, the effect of exercise training on adipose tissue oxygenation is worth further investigation, as it is very likely that exercise training stimulates adipose tissue angiogenesis and increases blood flow, thereby reducing hypoxia and the associated chronic inflammation in adipose tissue of obese individuals. PMID:23494259

  20. Effects of exercise training on chronic inflammation in obesity : current evidence and potential mechanisms.

    Science.gov (United States)

    You, Tongjian; Arsenis, Nicole C; Disanzo, Beth L; Lamonte, Michael J

    2013-04-01

    Chronic, systemic inflammation is an independent risk factor for several major clinical diseases. In obesity, circulating levels of inflammatory markers are elevated, possibly due to increased production of pro-inflammatory cytokines from several tissues/cells, including macrophages within adipose tissue, vascular endothelial cells and peripheral blood mononuclear cells. Recent evidence supports that adipose tissue hypoxia may be an important mechanism through which enlarged adipose tissue elicits local tissue inflammation and further contributes to systemic inflammation. Current evidence supports that exercise training, such as aerobic and resistance exercise, reduces chronic inflammation, especially in obese individuals with high levels of inflammatory biomarkers undergoing a longer-term intervention. Several studies have reported that this effect is independent of the exercise-induced weight loss. There are several mechanisms through which exercise training reduces chronic inflammation, including its effect on muscle tissue to generate muscle-derived, anti-inflammatory 'myokine', its effect on adipose tissue to improve hypoxia and reduce local adipose tissue inflammation, its effect on endothelial cells to reduce leukocyte adhesion and cytokine production systemically, and its effect on the immune system to lower the number of pro-inflammatory cells and reduce pro-inflammatory cytokine production per cell. Of these potential mechanisms, the effect of exercise training on adipose tissue oxygenation is worth further investigation, as it is very likely that exercise training stimulates adipose tissue angiogenesis and increases blood flow, thereby reducing hypoxia and the associated chronic inflammation in adipose tissue of obese individuals.

  1. Pulmonary hypertension in chronic obstructive and interstitial lung diseases.

    Science.gov (United States)

    Andersen, Charlotte U; Mellemkjær, Søren; Nielsen-Kudsk, Jens Erik; Bendstrup, Elisabeth; Hilberg, Ole; Simonsen, Ulf

    2013-10-01

    The purpose of the present review is to summarize the current knowledge on PH in relation to COPD and ILD from a clinical perspective with emphasis on diagnosis, biomarkers, prevalence, impact, treatment, and practical implications. PH in COPD and ILD is associated with a poor prognosis, and is considered one of the most frequent types of PH. However, the prevalence of PH among patients with COPD and ILD is not clear. The diagnosis of PH in chronic lung disease is often established by echocardiographic screening, but definitive diagnosis requires right heart catheterization, which is not systematically performed in clinical practice. Given the large number of patients with chronic lung disease, biomarkers to preclude or increase suspicion of PH are needed. NT-proBNP may be used as a rule-out test, but biomarkers with a high specificity for PH are still required. It is not known whether specific treatment with existent drugs effective in pulmonary arterial hypertension (PAH) is beneficial in lung disease related PH. Studies investigating existing PAH drugs in animal models of lung disease related PH have indicated a positive effect, and so have case reports and open label studies. However, treatment with systemically administered pulmonary vasodilators implies the risk of worsening the ventilation-perfusion mismatch in patients with lung disease. Inhaled vasodilators may be better suited for PH in lung disease, but new treatment modalities are also required. PMID:23849967

  2. Plasma 25-hydroxyvitamin D, lung function and risk of chronic obstructive pulmonary disease

    DEFF Research Database (Denmark)

    Afzal, Shoaib; Lange, Peter; Bojesen, Stig Egil;

    2014-01-01

    25-hydroxyvitamin D (25(OH)D) may be associated with lung function through modulation of pulmonary protease-antiprotease imbalance, airway inflammation, lung remodelling and oxidative stress. We examined the association of plasma 25(OH)D levels with lung function, lung function decline and risk o...

  3. Substance P at the Nexus of Mind and Body in Chronic Inflammation and Affective Disorders

    Science.gov (United States)

    Rosenkranz, Melissa A.

    2007-01-01

    For decades, research has demonstrated that chronic diseases characterized by dysregulation of inflammation are particularly susceptible to exacerbation by stress and emotion. Likewise, rates of depression and anxiety are overrepresented in individuals suffering from chronic inflammatory disease. In recent years, substance P has been implicated in…

  4. An Uncaria tomentosa (cat's claw) extract protects mice against ozone-induced lung inflammation.

    Science.gov (United States)

    Cisneros, Francisco J; Jayo, Manuel; Niedziela, Linda

    2005-01-15

    Ozone (O(3)) inhalation has been associated with respiratory tract inflammation and lung functional alterations. To characterize the O(3)-induced lung inflammation in mice, the effective dose and exposure time were determined. Total protein levels of bronchoalveolar lavage fluid (BALF), cytological smears, and lung histopathology and morphometry were used to assess and measure the degree of pulmonary inflammation in the mouse model. Ozone inhalation caused acute pneumonitis that was characterized by a high number of infiltrating neutrophils (PMNs) immediately after exposure and increased levels of protein in BALF in mice killed 8h after O(3) exposure. The anti-inflammatory properties of Uncaria tomentosa (UT) have been documented previously. To evaluate the anti-inflammatory effects of UT, male mice were given an UT extract for 8 days, exposed to O(3), and killed 0 or 8 h after O(3) exposure. When compared to untreated controls, UT-treated mice had significantly (p < 0.05) lower levels of protein in BALF, lower degree of epithelial necrosis, higher number of intact epithelial cell nuclei in bronchial wall, and decreased number of PMNs in the bronchiolar lumen. Therefore, UT extract appeared to prevent O(3)-induced respiratory inflammation in male mice.

  5. Pendelluft in Chronic Obstructive Lung Disease Measured with Lung Sounds

    Directory of Open Access Journals (Sweden)

    Andrey Vyshedskiy

    2012-01-01

    Full Text Available Objective. The phenomenon of pendelluft was described over five decades ago. In patients with regional variations in resistance and elastance, gas moves at the beginning of inspiration out of some alveoli into others. Gas moves in the opposite direction at the end of inspiration. The objective of this study was to apply the method of lung sounds mapping, which is known to provide regional information about gas flow, to study pendelluft in COPD patients. Methods. A 16-channel lung sound analyzer was used to collect sounds from patients with COPD (n=90 and age-matched normals (n=90. Pendelluft at the beginning of inspiration is expected to result in vesicular sounds leading the tracheal sound by a few milliseconds. Pendelluft at the end of inspiration is expected to result in vesicular sounds lagging the tracheal sound. These lead and lag times were calculated for the 14 chest wall sites. Results. The lead time was significantly longer in COPD patients: 123±107 ms versus 48±59 ms in controls (P<0.0001. The lag time was also significantly longer in COPD patients: 269±249 ms in COPD patients versus 147±124 ms in controls (P<0.0001. When normalized by the duration of the inspiration at the trachea, the lead was 14±13% for COPD versus 4±5% for controls (P<0.0001. The lag was 28±25% for COPD versus 13±12% for controls (P<0.0001. Both lead and lag correlated moderately with the GOLD stage (correlation coefficient 0.43. Conclusion. Increased lead and lag times in COPD patients are consistent with the phenomenon of pendelluft as has been observed by other methods.

  6. Regional pulmonary inflammation in an endotoxemic ovine acute lung injury model.

    Science.gov (United States)

    Fernandez-Bustamante, A; Easley, R B; Fuld, M; Mulreany, D; Chon, D; Lewis, J F; Simon, B A

    2012-08-15

    The regional distribution of inflammation during acute lung injury (ALI) is not well known. In an ovine ALI model we studied regional alveolar inflammation, surfactant composition, and CT-derived regional specific volume change (sVol) and specific compliance (sC). 18 ventilated adult sheep received IV lipopolysaccharide (LPS) until severe ALI was achieved. Blood and bronchoalveolar lavage (BAL) samples from apical and basal lung regions were obtained at baseline and injury time points, for analysis of cytokines (IL-6, IL-1β), BAL protein and surfactant composition. Whole lung CT images were obtained in 4 additional sheep. BAL protein and IL-1β were significantly higher in injured apical vs. basal regions. No significant regional surfactant composition changes were observed. Baseline sVol and sC were lower in apex vs. base; ALI enhanced this cranio-caudal difference, reaching statistical significance only for sC. This study suggests that apical lung regions show greater inflammation than basal ones during IV LPS-induced ALI which may relate to differences in regional mechanical events.

  7. Chronic aspergillosis of the lungs: Unravelling the terminology and radiology

    Energy Technology Data Exchange (ETDEWEB)

    Desai, S.R.; Hedayati, V.; Patel, K. [King' s College Hospital NHS Foundation Trust, The Department of Radiology, King' s Health Partners, King' s College London, London (United Kingdom); Hansell, D.M. [The Royal Brompton and Harefield NHS Foundation Trust, Department of Radiology, London (United Kingdom)

    2015-10-15

    The propensity for Aspergillus spp. to cause lung disease has long been recognised but the satisfactory classification of these disorders is challenging. The problems caused by invasive disease in severely neutropenic patients, saprophytic infection of pre-existing fibrotic cavities and allergic reactions to Aspergillus are well documented. In contrast, a more chronic form of Aspergillus-related lung disease that has the potential to cause significant morbidity and mortality is under-reported. The symptoms of this form of Aspergillus infection may be non-specific and the radiologist may be the first to suspect a diagnosis of chronic pulmonary aspergillosis. The current review considers the classification conundrums in diseases caused by Aspergillus spp. and discusses the typical clinical and radiological profile of patients with chronic pulmonary aspergillosis. (orig.)

  8. Deficiency of phospholipase A2 receptor exacerbates ovalbumin-induced lung inflammation.

    Science.gov (United States)

    Tamaru, Shun; Mishina, Hideto; Watanabe, Yosuke; Watanabe, Kazuhiro; Fujioka, Daisuke; Takahashi, Soichiro; Suzuki, Koji; Nakamura, Takamitsu; Obata, Jun-Ei; Kawabata, Kenichi; Yokota, Yasunori; Murakami, Makoto; Hanasaki, Kohji; Kugiyama, Kiyotaka

    2013-08-01

    Secretory phospholipase A2 (sPLA2) plays a critical role in the genesis of lung inflammation through proinflammatory eicosanoids. A previous in vitro experiment showed a possible role of cell surface receptor for sPLA2 (PLA2R) in the clearance of extracellular sPLA2. PLA2R and groups IB and X sPLA2 are expressed in the lung. This study examined a pathogenic role of PLA2R in airway inflammation using PLA2R-deficient (PLA2R(-/-)) mice. Airway inflammation was induced by immunosensitization with OVA. Compared with wild-type (PLA2R(+/+)) mice, PLA2R(-/-) mice had a significantly greater infiltration of inflammatory cells around the airways, higher levels of groups IB and X sPLA2, eicosanoids, and Th2 cytokines, and higher numbers of eosinophils and neutrophils in bronchoalveolar lavage fluid after OVA treatment. In PLA2R(-/-) mice, intratracheally instilled [(125)I]-labeled sPLA2-IB was cleared much more slowly from bronchoalveolar lavage fluid compared with PLA2R(+/+) mice. The degradation of the instilled [(125)I]-labeled sPLA2-IB, as assessed by trichloroacetic acid-soluble radioactivity in bronchoalveolar lavage fluid after instillation, was lower in PLA2R(-/-) mice than in PLA2R(+/+) mice. In conclusion, PLA2R deficiency increased sPLA2-IB and -X levels in the lung through their impaired clearance from the lung, leading to exaggeration of lung inflammation induced by OVA treatment in a murine model.

  9. Genomic instability in quartz dust exposed rat lungs: Is inflammation responsible?

    Science.gov (United States)

    Albrecht, C.; Knaapen, A. M.; Cakmak Demircigil, G.; Coskun, Erdem; van Schooten, F. J.; Borm, P. J. A.; Schins, R. P. F.

    2009-02-01

    Exposure to quartz dusts has been associated with lung cancer and fibrosis. Although the responsible mechanisms are not completely understood, progressive inflammation with associated induction of persistent oxidative stress has been discussed as a key event for these diseases. Previously we have evaluated the kinetics of pulmonary inflammation in the rat model following a single intratracheal instillation of 2mg DQ12 quartz, either in its native form or upon its surface modification with polyvinylpyridine-N-oxide or aluminium lactate. This model has been applied now to evaluate the role of inflammation in the kinetics of induction of DNA damage and response at 3, 7, 28, and 90 days after treatment. Bronchoalveolar lavage (BAL) cell counts and differentials as well as BAL fluid myeloperoxidase activity were used as markers of inflammation. Whole lung homogenate was investigated to determine the induction of the oxidative and pre-mutagenic DNA lesion 8-hydroxy-2-deoxy-guanosine (8-OHdG) by HPLC/ECD, while mRNA and protein expression of oxidative stress and DNA damage response genes including hemeoxygenase-1 (HO-1) and apurinic/apyrimidinic endonuclease (APE/Ref-1) were evaluated using Western blotting and real time PCR. Isolated lung epithelial cells from the treated rats were used for DNA strand breakage analysis using the alkaline comet assay as well as for micronucleus scoring in May-Gruenwald-Giemsa stained cytospin preparations. In the rats that were treated with quartz, no increased 8-OHdG levels were observed, despite the presence of a marked and persistent inflammation. However, DNA strand breakage in the lung epithelial cells of the quartz treated rats was significantly enhanced at 3 days, but not at 28 days. Moreover, significantly enhanced micronucleus frequencies were observed for all four time points investigated. In the animals that were treated with the PVNO modified quartz, micronuclei scores did not differ from controls, while in those treated with

  10. Inflammation in Achromobacter xylosoxidans infected cystic fibrosis patients

    DEFF Research Database (Denmark)

    Hansen, C. R.; Pressler, T.; Nielsen, K. G.;

    2010-01-01

    BACKGROUND: Achromobacter xylosoxidans infection may cause conspicuous chronic pulmonary inflammation in cystic fibrosis (CF) patients similar to Pseudomonas aeruginosa and the Burkholderia cepacia complex (Bcc). Evolution in lung function was compared in chronically infected patients. Cytokine...

  11. Impact of interleukin-6 on hypoxia-induced pulmonary hypertension and lung inflammation in mice

    Directory of Open Access Journals (Sweden)

    Izziki Mohamed

    2009-01-01

    Full Text Available Abstract Background Inflammation may contribute to the pathogenesis of various forms of pulmonary hypertension (PH. Recent studies in patients with idiopathic PH or PH associated with underlying diseases suggest a role for interleukin-6 (IL-6. Methods To determine whether endogenous IL-6 contributes to mediate hypoxic PH and lung inflammation, we studied IL-6-deficient (IL-6-/- and wild-type (IL-6+/+ mice exposed to hypoxia for 2 weeks. Results Right ventricular systolic pressure, right ventricle hypertrophy, and the number and media thickness of muscular pulmonary vessels were decreased in IL-6-/- mice compared to wild-type controls after 2 weeks' hypoxia, although the pressure response to acute hypoxia was similar in IL-6+/+ and IL-6-/- mice. Hypoxia exposure of IL-6+/+ mice led to marked increases in IL-6 mRNA and protein levels within the first week, with positive IL-6 immunostaining in the pulmonary vessel walls. Lung IL-6 receptor and gp 130 (the IL-6 signal transducer mRNA levels increased after 1 and 2 weeks' hypoxia. In vitro studies of cultured human pulmonary-artery smooth-muscle-cells (PA-SMCs and microvascular endothelial cells revealed prominent synthesis of IL-6 by PA-SMCs, with further stimulation by hypoxia. IL-6 also markedly stimulated PA-SMC migration without affecting proliferation. Hypoxic IL-6-/- mice showed less inflammatory cell recruitment in the lungs, compared to hypoxic wild-type mice, as assessed by lung protein levels and immunostaining for the specific macrophage marker F4/80, with no difference in lung expression of adhesion molecules or cytokines. Conclusion These data suggest that IL-6 may be actively involved in hypoxia-induced lung inflammation and pulmonary vascular remodeling in mice.

  12. Contribution of Inflammation to Vascular Disease in Chronic Kidney Disease Patients

    Directory of Open Access Journals (Sweden)

    Suliman Mohamed

    2008-01-01

    Full Text Available Chronic kidney disease (CKD is characterized by an exceptionally high mortality rate, much of which results from cardiovascular disease (CVD. Chronic low-grade inflammation, as evidenced by increased levels of pro-inflammatory cytokines and C-reactive protein (CRP, is a common feature of CKD and may cause atherosclerotic CVD through various pathogenetic mechanisms. Evidence suggests that persistent inflammation may also be a risk factor for progression of CKD, which may result in a vicious inflammation-driven circle. The causes of inflammation in CKD are multifactorial. The influence of various comorbidities may contribute to inflammation in the setting of progressive loss of renal function. Available data suggest that pro-inflammatory cytokines also play a central role in the genesis of the metabolic syndrome. There is a lack of epidemiological data on the prevalence and consequences of inflammation in relation to protein-energy wasting (PEW and CVD in CKD patients from developing countries. The ′westernization′ of nutritional intakes and changes of life style besides the high prevalence of chronic infections in developing countries are possible additive contributors to a high prevalence of inflammation, PEW and CVD among CKD patients. Also, genetic differences may affect inflammatory responses and nutritional status and, thus, the susceptibility to CVD in different regions.

  13. Pulmonary hypertension in chronic interstitial lung diseases

    Directory of Open Access Journals (Sweden)

    Antonella Caminati

    2013-09-01

    Full Text Available Pulmonary hypertension (PH is a common complication of interstitial lung diseases (ILDs, particularly in idiopathic pulmonary fibrosis and ILD associated with connective tissue disease. However, other lung diseases, such as combined pulmonary fibrosis and emphysema syndrome, pulmonary Langerhans cell histiocytosis, and lymphangioleiomyomatosis, may also include PH in their clinical manifestations. In all of these diseases, PH is associated with reduced exercise capacity and poor prognosis. The degree of PH in ILDs is typically mild-to-moderate. However, some of these patients may develop a disproportionate increase in PH that cannot be justified solely by hypoxia and parenchymal injury: this condition has been termed “out-of-proportion” PH. The pathogenesis of PH in these diseases is various, incompletely understood and may be multifactorial. The clinical suspicion (i.e. increased dyspnoea, low diffusion capacity and echocardiographic assessment are the first steps towards proper diagnosis of PH; however, right heart catheterisation remains the current gold standard for diagnosis of PH. At present, no specific therapies have been approved for the treatment of PH in patients with ILDs.

  14. Lung lobar volume in patients with chronic interstitial pneumonia

    International Nuclear Information System (INIS)

    We measured lung lobar volume by using helical computed tomography (HCT) in 23 patients with idiopathic interstitial pneumonia (IIP), 7 patients with chronic interstitial pneumonia associated with collagen vascular disease (CVD-IP), and 5 healthy volunteers HCT scanning was done at the maximal inspiratory level and the resting end-expiratory level. To measure lung lobar volume, we traced the lobar margin on HCT images with a digitizer and calculated the lobar volume with a personal computer. The lower lobar volume and several factors influencing it in chronic interstitial pneumonia were studied. At the maximal inspiratory level, the lower lobar volume as a percent of the whole lung volume was 46.8±4.13% (mean ± SD) in the volunteers, 39.5±6.19% in the patients with IIP, and 27.7±7. 86% in the patients with CVD-IP. The lower lobar volumes in the patients were significantly lower than in the volunteers. Patients with IIP in whom autoantibody tests were positive had lower lobar volumes that were very low and were similar to those of patients with CVD-IP. These data suggest that collagen vascular disease may develop in patients with interstitial pneumonia. The patients with IIP who had emphysematous changes on the CT scans had smaller decreases in total lung capacity and lower ratios of forced expiratory volume in one second to forced vital capacity than did those who had no emphysematous changes, those two groups did not differ in the ratio of lower lobar volume to whole lung volume. This suggests that emphysematous change is not factor influencing lower lobar volume in patients with chronic interstitial pneumonia. We conclude that chronic interstitial pneumonia together with very low values for lower lobar volume may be a pulmonary manifestation of collagen vascular disease. (author)

  15. Potential contribution of Type I lung epithelial cells to chronic neonatal lung disease

    Directory of Open Access Journals (Sweden)

    Henry J. Rozycki

    2014-05-01

    Full Text Available The alveolar surface is covered by large flat Type I cells (alveolar epithelial cells 1, AEC1. The normal physiological function of AEC1s involves gas exchange, based on their location in approximation to the capillary endothelium and their thinness, and in ion and water flux, as shown by the presence of solute active transport proteins, water channels, and impermeable tight junctions between cells. With the recent ability to produce relatively pure cultures of AEC1 cells, new functions have been described. These may be relevant to lung injury, repair and the abnormal development that characterizes bronchopulmonary dysplasia. To hypothesize a potential role for AEC1 in the development of lung injury and abnormal repair/development in premature lungs, evidence is presented for their presence in the developing lung, how their source may not be the Type II cell (AEC2 as has been assumed for forty years, and how the cell can be damaged by same type of stressors as those which lead to bronchopulmonary dysplasia (BPD. Recent work shows that the cells are part of the innate immune response, capable of producing pro-inflammatory mediators, which could contribute to the increase in inflammation seen in early bronchopulmonary dysplasia. One of the receptors found exclusively on AEC1 cells in the lung, called RAGE, may also have a role in increased inflammation, and to alveolar simplification. While the current evidence for AEC1 involvement in BPD is circumstantial and limited at present, the accumulating data supports several hypotheses and questions regarding potential differences in the behavior of AEC1 cells from newborn and premature lung compared with the adult lung.

  16. Prostatic inflammation induces fibrosis in a mouse model of chronic bacterial infection.

    Directory of Open Access Journals (Sweden)

    Letitia Wong

    Full Text Available Inflammation of the prostate is strongly correlated with development of lower urinary tract symptoms and several studies have implicated prostatic fibrosis in the pathogenesis of bladder outlet obstruction. It has been postulated that inflammation induces prostatic fibrosis but this relationship has never been tested. Here, we characterized the fibrotic response to inflammation in a mouse model of chronic bacterial-induced prostatic inflammation. Transurethral instillation of the uropathogenic E. coli into C3H/HeOuJ male mice induced persistent prostatic inflammation followed by a significant increase in collagen deposition and hydroxyproline content. This fibrotic response to inflammation was accompanied with an increase in collagen synthesis determined by the incorporation of 3H-hydroxyproline and mRNA expression of several collagen remodeling-associated genes, including Col1a1, Col1a2, Col3a1, Mmp2, Mmp9, and Lox. Correlation analysis revealed a positive correlation of inflammation severity with collagen deposition and immunohistochemical staining revealed that CD45+VIM+ fibrocytes were abundant in inflamed prostates at the time point coinciding with increased collagen synthesis. Furthermore, flow cytometric analysis demonstrated an increased percentage of these CD45+VIM+ fibrocytes among collagen type I expressing cells. These data show-for the first time-that chronic prostatic inflammation induces collagen deposition and implicates fibrocytes in the fibrotic process.

  17. Lung angiotensin converting enzyme activity in chronically hypoxic rats.

    OpenAIRE

    Kay, J M; Keane, P. M.; Suyama, K L; Gauthier, D.

    1985-01-01

    A study was carried out to test the hypothesis that the reduced lung angiotensin converting enzyme (ACE) activity which occurs in chronic hypoxia is related to the development of pulmonary hypertension rather than to hypoxia per se. Right ventricular mean systolic pressure (Prvs, mm Hg) and ACE activity (nmol/mg protein/min) in lung tissue homogenates were measured in seven groups of four rats placed in a hypobaric chamber (380 mm Hg; 51 kPa) for two to 24 days. Identical measurements were ma...

  18. Effect of Hedera helix on lung histopathology in chronic asthma.

    OpenAIRE

    Arzu Babayigit Hocaoglu; Ozkan Karaman; Duygu Olmez Erge; Guven Erbil; Osman Yilmaz; Bijen Kivcak; H Alper Bagriyanik; Nevin Uzuner

    2012-01-01

    Hedera helix  is widely used to treat bronchial asthma for many years. However, effects of this herb on lung histopathology is still far from clear. We aimed to determine the effect of oral administration of Hedera helix on lung histopathology in a murine model of chronic asthma.BALB/c  mice  were  divided  into  four  groups;   I  (Placebo),  II  (Hedera  helix), III (Dexamethasone) and IV (Control). All mice except controls were sensitized and challenged with ovalbumin. Then, mice in group ...

  19. Global analysis of gene expression in pulmonary fibrosis reveals distinct programs regulating lung inflammation and fibrosis

    Science.gov (United States)

    Kaminski, Naftali; Allard, John D.; Pittet, Jean F.; Zuo, Fengrong; Griffiths, Mark J. D.; Morris, David; Huang, Xiaozhu; Sheppard, Dean; Heller, Renu A.

    2000-02-01

    The molecular mechanisms of pulmonary fibrosis are poorly understood. We have used oligonucleotide arrays to analyze the gene expression programs that underlie pulmonary fibrosis in response to bleomycin, a drug that causes lung inflammation and fibrosis, in two strains of susceptible mice (129 and C57BL/6). We then compared the gene expression patterns in these mice with 129 mice carrying a null mutation in the epithelial-restricted integrin 6 subunit (6/-), which develop inflammation but are protected from pulmonary fibrosis. Cluster analysis identified two distinct groups of genes involved in the inflammatory and fibrotic responses. Analysis of gene expression at multiple time points after bleomycin administration revealed sequential induction of subsets of genes that characterize each response. The availability of this comprehensive data set should accelerate the development of more effective strategies for intervention at the various stages in the development of fibrotic diseases of the lungs and other organs.

  20. Familial idiopathic pulmonary fibrosis. Evidence of lung inflammation in unaffected family members

    International Nuclear Information System (INIS)

    We evaluated 17 clinically unaffected members of three families with an autosomal dominant form of idiopathic pulmonary fibrosis for evidence of alveolar inflammation. Each person in the study was examined by gallium-67 scanning for a general estimate of pulmonary inflammation, and by bronchoalveolar lavage for characterization of the types of recovered cells and their state of activation. Eight of the 17 subjects had evidence of alveolar inflammation on the lavage studies. Supporting data included increased numbers of neutrophils and activated macrophages that released one or more neutrophil chemoattractants, and growth factors for lung fibroblasts--findings similar to those observed in patients with overt idiopathic pulmonary fibrosis. Four of these eight also had a positive gallium scan; in all the other clinically unaffected subjects the scan was normal. During a follow-up of two to four years in seven of the eight subjects who had evidence of inflammation, no clinical evidence of pulmonary fibrosis has appeared. These results indicate that alveolar inflammation occurs in approximately half the clinically unaffected family members at risk of inheriting autosomal dominant idiopathic pulmonary fibrosis. Whether these persons with evidence of pulmonary inflammation but no fibrosis will proceed to have clinically evident pulmonary fibrosis is not yet known

  1. Milano summer particulate matter (PM10 triggers lung inflammation and extra pulmonary adverse events in mice.

    Directory of Open Access Journals (Sweden)

    Francesca Farina

    Full Text Available Recent studies have suggested a link between particulate matter (PM exposure and increased mortality and morbidity associated with pulmonary and cardiovascular diseases; accumulating evidences point to a new role for air pollution in CNS diseases. The purpose of our study is to investigate PM10sum effects on lungs and extra pulmonary tissues. Milano PM10sum has been intratracheally instilled into BALB/c mice. Broncho Alveolar Lavage fluid, lung parenchyma, heart and brain were screened for markers of inflammation (cell counts, cytokines, ET-1, HO-1, MPO, iNOS, cytotoxicity (LDH, ALP, Hsp70, Caspase8-p18, Caspase3-p17 for a putative pro-carcinogenic marker (Cyp1B1 and for TLR4 pathway activation. Brain was also investigated for CD68, TNF-α, GFAP. In blood, cell counts were performed while plasma was screened for endothelial activation (sP-selectin, ET-1 and for inflammation markers (TNF-α, MIP-2, IL-1β, MPO. Genes up-regulation (HMOX1, Cyp1B1, IL-1β, MIP-2, MPO and miR-21 have been investigated in lungs and blood. Inflammation in the respiratory tract of PM10sum-treated mice has been confirmed in BALf and lung parenchyma by increased PMNs percentage, increased ET-1, MPO and cytokines levels. A systemic spreading of lung inflammation in PM10sum-treated mice has been related to the increased blood total cell count and neutrophils percentage, as well as to increased blood MPO. The blood-endothelium interface activation has been confirmed by significant increases of plasma ET-1 and sP-selectin. Furthermore PM10sum induced heart endothelial activation and PAHs metabolism, proved by increased ET-1 and Cyp1B1 levels. Moreover, PM10sum causes an increase in brain HO-1 and ET-1. These results state the translocation of inflammation mediators, ultrafine particles, LPS, metals associated to PM10sum, from lungs to bloodstream, thus triggering a systemic reaction, mainly involving heart and brain. Our results provided additional insight into the toxicity

  2. Heat Shock Protein 90 Inhibitors Prolong Survival, Attenuate Inflammation, and Reduce Lung Injury in Murine Sepsis

    OpenAIRE

    Chatterjee, Anuran; Dimitropoulou, Christiana; Drakopanayiotakis, Fotios; ANTONOVA, Galina; Snead, Connie; Cannon, Joseph; Venema, Richard C.; Catravas, John D.

    2007-01-01

    Rationale: Severe sepsis is the leading cause of death for patients in intensive care units. Patients with severe sepsis develop multiple organ failure, including acute lung injury (ALI), resulting from a deregulated inflammatory response. Inhibitors of the ubiquitous chaperone, heat shock protein 90 (Hsp90), block the activity of certain proinflammatory mediators in vitro. We hypothesized that Hsp90 inhibitors may ameliorate the inflammation and ALI associated with severe sepsis.

  3. Spred-2 Deficiency Exacerbates Lipopolysaccharide-Induced Acute Lung Inflammation in Mice

    OpenAIRE

    Yang Xu; Toshihiro Ito; Soichiro Fushimi; Sakuma Takahashi; Junya Itakura; Ryojiro Kimura; Miwa Sato; Megumi Mino; Akihiko Yoshimura; Akihiro Matsukawa

    2014-01-01

    BACKGROUND: Acute respiratory distress syndrome (ARDS) is a severe and life-threatening acute lung injury (ALI) that is caused by noxious stimuli and pathogens. ALI is characterized by marked acute inflammation with elevated alveolar cytokine levels. Mitogen-activated protein kinase (MAPK) pathways are involved in cytokine production, but the mechanisms that regulate these pathways remain poorly characterized. Here, we focused on the role of Sprouty-related EVH1-domain-containing protein (Spr...

  4. Platelet activation and aggregation promote lung inflammation and influenza virus pathogenesis.

    OpenAIRE

    Le, Vuong Ba; Schneider, Jochen; Boergeling, Yvonne; Berri, Fatma; Ducatez, Mariette; GUERIN, Jean-Luc; Adrian, Iris; Errazuriz-Cerda, Elisabeth; frasquilho, sonia; Antunes, Laurent; Lina, Bruno; Bordet, Jean-Claude; Jandrot-Perrus, Martine; Ludwig, Stephan; Riteau, Beatrice

    2015-01-01

    RATIONALE: The hallmark of severe influenza virus infection is excessive inflammation of the lungs. Platelets are activated during influenza, but their role in influenza virus pathogenesis and inflammatory responses is unknown. OBJECTIVES: To determine the role of platelets during influenza A virus infections and propose new therapeutics against influenza. METHODS: We used targeted gene deletion approaches and pharmacologic interventions to investigate the role of platelets during influenza v...

  5. Neutrophil DNA contributes to the antielastase barrier during acute lung inflammation.

    Science.gov (United States)

    Balloy, Viviane; Sallenave, Jean-Michel; Crestani, Bruno; Dehoux, Monique; Chignard, Michel

    2003-06-01

    During acute lung inflammation, the airspaces are invaded by circulating neutrophils. These may then injure tissues through the release of elastase. Different natural specific inhibitors such as alpha1-proteinase inhibitor, secretory leukocyte proteinase inhibitor, and elafin are nonetheless able to counteract the enzymatic activity of elastase. The present study was undertaken to assess the role of these different inhibitors in the intrinsic antielastase barrier during lipopolysaccharide-induced lung inflammation in mice. Upon intranasal administration of lipopolysaccharide to mice, the antielastase activity recovered from bronchoalveolar lavage fluids (BALF) increases progressively up to 48 h (7-fold) and returns to the basal level within 72 h. By contrast, when the same experiments are performed with neutropenic mice (pretreatment with an antigranulocyte antibody, or vinblastine), the increase is almost totally absent. Ultrafiltration of BALF through 100 kD cutoff membranes shows that the activity remains in the retentate, thus ruling out a role for native alpha1-proteinase inhibitor, secretory leukocyte proteinase inhibitor, and elafin. Gel filtration and fraction analysis show that the material eluted with a Mr of 600 kD. Agarose gel electrophoresis and ethidium bromide staining reveal that the activity corresponds to the presence a large amount of DNA. Interestingly, DNase treatment of the active fraction suppresses the antielastase activity. Analysis of BALF from patients with acute lung inflammation shows the presence of DNA with antielastase activity. We therefore concluded that during acute lung inflammation, the recruitment of neutrophils in the airspaces accounts for the increased presence of DNA, which in turn contributes to the antielastase barrier. PMID:12600833

  6. The triterpenoid CDDO-Me inhibits bleomycin-induced lung inflammation and fibrosis.

    Directory of Open Access Journals (Sweden)

    Ajit A Kulkarni

    Full Text Available Pulmonary Fibrosis (PF is a devastating progressive disease in which normal lung structure and function is compromised by scarring. Lung fibrosis can be caused by thoracic radiation, injury from chemotherapy and systemic diseases such as rheumatoid arthritis that involve inflammatory responses. CDDO-Me (Methyl 2-cyano-3,12-dioxooleana-1,9(11dien-28-oate, Bardoxolone methyl is a novel triterpenoid with anti-fibrotic and anti-inflammatory properties as shown by our in vitro studies. Based on this evidence, we hypothesized that CDDO-Me would reduce lung inflammation, fibrosis and lung function impairment in a bleomycin model of lung injury and fibrosis. To test this hypothesis, mice received bleomycin via oropharyngeal aspiration (OA on day zero and CDDO-Me during the inflammatory phase from days -1 to 9 every other day. Bronchoalveolar lavage fluid (BALF and lung tissue were harvested on day 7 to evaluate inflammation, while fibrosis and lung function were evaluated on day 21. On day 7, CDDO-Me reduced total BALF protein by 50%, alveolar macrophage infiltration by 40%, neutrophil infiltration by 90% (p≤0.01, inhibited production of the inflammatory cytokines KC and IL-6 by over 90% (p≤0.001, and excess production of the pro-fibrotic cytokine TGFβ by 50%. CDDO-Me also inhibited α-smooth muscle actin and fibronectin mRNA by 50% (p≤0.05. On day 21, CDDO-Me treatment reduced histological fibrosis, collagen deposition and αSMA production. Lung function was significantly improved at day 21 by treatment with CDDO-Me, as demonstrated by respiratory rate and dynamic compliance. These new findings reveal that CDDO-Me exhibits potent anti-fibrotic and anti-inflammatory properties in vivo. CDDO-Me is a potential new class of drugs to arrest inflammation and ameliorate fibrosis in patients who are predisposed to lung injury and fibrosis incited by cancer treatments (e.g. chemotherapy and radiation and by systemic autoimmune diseases.

  7. Soluble CD59 is a Novel Biomarker for the Prediction of Obstructive Chronic Lung Allograft Dysfunction After Lung Transplantation.

    Science.gov (United States)

    Budding, Kevin; van de Graaf, Eduard A; Kardol-Hoefnagel, Tineke; Kwakkel-van Erp, Johanna M; Luijk, Bart D; Oudijk, Erik-Jan D; van Kessel, Diana A; Grutters, Jan C; Hack, C Erik; Otten, Henderikus G

    2016-05-24

    CD59 is a complement regulatory protein that inhibits membrane attack complex formation. A soluble form of CD59 (sCD59) is present in various body fluids and is associated with cellular damage after acute myocardial infarction. Lung transplantation (LTx) is the final treatment for end-stage lung diseases, however overall survival is hampered by chronic lung allograft dysfunction development, which presents itself obstructively as the bronchiolitis obliterans syndrome (BOS). We hypothesized that, due to cellular damage and activation during chronic inflammation, sCD59 serum levels can be used as biomarker preceding BOS development. We analyzed sCD59 serum concentrations in 90 LTx patients, of whom 20 developed BOS. We observed that BOS patients exhibited higher sCD59 serum concentrations at the time of diagnosis compared to clinically matched non-BOS patients (p = 0.018). Furthermore, sCD59 titers were elevated at 6 months post-LTx (p = 0.0020), when patients had no BOS-related symptoms. Survival-analysis showed that LTx patients with sCD59 titers ≥400 pg/ml 6 months post-LTx have a significant (p < 0.0001) lower chance of BOS-free survival than patients with titers ≤400 pg/ml, 32% vs. 80% respectively, which was confirmed by multivariate analysis (hazard ratio 6.2, p < 0.0001). We propose that circulating sCD59 levels constitute a novel biomarker to identify patients at risk for BOS following LTx.

  8. A New Mouse Model That Spontaneously Develops Chronic Liver Inflammation and Fibrosis

    Science.gov (United States)

    Fransén-Pettersson, Nina; Duarte, Nadia; Nilsson, Julia; Lundholm, Marie; Mayans, Sofia; Larefalk, Åsa; Hannibal, Tine D.; Hansen, Lisbeth; Schmidt-Christensen, Anja; Ivars, Fredrik; Cardell, Susanna; Palmqvist, Richard; Rozell, Björn

    2016-01-01

    Here we characterize a new animal model that spontaneously develops chronic inflammation and fibrosis in multiple organs, the non-obese diabetic inflammation and fibrosis (N-IF) mouse. In the liver, the N-IF mouse displays inflammation and fibrosis particularly evident around portal tracts and central veins and accompanied with evidence of abnormal intrahepatic bile ducts. The extensive cellular infiltration consists mainly of macrophages, granulocytes, particularly eosinophils, and mast cells. This inflammatory syndrome is mediated by a transgenic population of natural killer T cells (NKT) induced in an immunodeficient NOD genetic background. The disease is transferrable to immunodeficient recipients, while polyclonal T cells from unaffected syngeneic donors can inhibit the disease phenotype. Because of the fibrotic component, early on-set, spontaneous nature and reproducibility, this novel mouse model provides a unique tool to gain further insight into the underlying mechanisms mediating transformation of chronic inflammation into fibrosis and to evaluate intervention protocols for treating conditions of fibrotic disorders. PMID:27441847

  9. Carbon nanotubes induce inflammation but decrease the production of reactive oxygen species in lung.

    Science.gov (United States)

    Crouzier, D; Follot, S; Gentilhomme, E; Flahaut, E; Arnaud, R; Dabouis, V; Castellarin, C; Debouzy, J C

    2010-06-01

    With the rapid spread of carbon nanotubes (CNTs) applications, the respiratory toxicity of these compounds has attracted the attention of many scientists. Several studies have reported that after lung administration, CNTs could induce granuloma, fibrosis, or inflammation. By comparison with the mechanisms involved with other toxic particles such as asbestos, this effect could be attributed to an increase of oxidative stress. The aim of the present work was to test this hypothesis in vivo. Mice were intranasally instilled with 1.5mg/kg of double walled carbon nanotubes (DWCNTs). Six, 24, or 48h after administration, inflammation and localisation of DWCNTs in lungs were microscopically observed. Local oxidative perturbations were investigated using ESR spin trapping experiments, and systemic inflammation was assessed by measuring the plasma concentration of cytokines TNF-alpha, IL-1alpha, IL-1beta, IL-6, IGF-1, Leptin, G-CSF, and VEGF. Examination of lungs and the elevation of proinflammatory cytokines in the plasma (Leptin and IL-6 at 6h) confirmed the induction of an inflammatory reaction. This inflammatory reaction was accompanied by a decrease in the local oxidative stress. This effect could be attributed to the scavenger capability of pure CNTs.

  10. Bystander suppression of allergic airway inflammation by lung resident memory CD8+ T cells

    Science.gov (United States)

    Marsland, Benjamin J.; Harris, Nicola L.; Camberis, Mali; Kopf, Manfred; Hook, Sarah M.; Le Gros, Graham

    2004-04-01

    CD8+ memory T cells have recently been recognized as playing a key role in natural immunity against unrelated viral infections, a phenomenon referred to as "heterologous antiviral immunity." We now provide data that the cellular immunological interactions that underlie such heterologous immunity can play an equally important role in regulating T helper 2 immune responses and protecting mucosal surfaces from allergen-induced inflammation. Our data show that CD8+ T cells, either retained in the lung after infection with influenza virus, or adoptively transferred via the intranasal route can suppress allergic airway inflammation. The suppression is mediated by IFN-, which acts to reduce the activation level, T helper 2 cytokine production, airways hyperresponsiveness, and migration of allergen-specific CD4+ T cells into the lung, whereas the systemic and draining lymph node responses remain unchanged. Of note, adoptive transfer of previously activated transgenic CD8+ T cells conferred protection against allergic airway inflammation, even in the absence of specific-antigen. Airway resident CD8+ T cells produced IFN- when directly exposed to conditioned media from activated dendritic cells or the proinflammatory cytokines IL-12 and IL-18. Taken together these data indicate that effector/memory CD8+ T cells present in the airways produce IFN- after inflammatory stimuli, independent of specific-antigen, and as a consequence play a key role in modifying the degree and frequency of allergic responses in the lung.

  11. Melatonin reduces acute lung inflammation, edema,and hemorrhage in heatstroke rats

    Institute of Scientific and Technical Information of China (English)

    Wen-shiann WU; Ming-ting CHOU; Chien-ming CHAO; Chen-kuei CHANG; Mao-tsun LIN; Ching-ping CHANG

    2012-01-01

    Aim:To assess the therapeutic effect of melatonin on heat-induced acute lung inflammation and injury in rats.Methods:Heatstroke was induced by exposing anesthetized rats to heat stress (36 ℃,100 min).Rats were treated with vehicle or melatonin (0.2,1,5 mg/kg) by intravenous administration 100 min after the initiatioin of heatstroke and were allowed to recover at room temperature (26 ℃).The acute lung injury was quantified by morphological examination and by determination of the volume of pleural exudates,the number of polymorphonuclear (PMN) cells,and the myeloperoxidase (MPO) activity.The concentrations of tumor necrosis factor,interleukin (IL)-1β,IL-6,and IL-10 in bronchoalveolar fluid (BALF) were measured by ELISA.Nitric oxide (NO)level was determined by Griess method.The levels of glutamate and lactate-to-pyruvate ratio were analyzed by CMA600 microdialysis analyzer.The concentrations of hydroxyl radicals were measured by a procedure based on the hydroxylation of sodium salicylates leading to the production of 2,3-dihydroxybenzoic acid (DHBA).Results:Melatonin (1 and 5 mg/kg ) significantly (i) prolonged the survival time of heartstroke rats (117 and 186 min vs 59 min); (ii)attenuated heatstroke-induced hyperthermia and hypotension; (iii) attenuated acute lung injury,including edema,neutrophil infiltration,and hemorrhage scores; (iv) down-regulated exudate volume,BALF PMN cell number,and MPO activity; (v) decreased the BALF levels of lung inflammation response cytokines like TNF-alpha,interleukin (IL)-1β,and IL-6 but further increased the level of an anti-inflammatory cytokine IL-10; (vi) reduced BALF levels of glutamate,lactate-to-pyruvate ratio,NO,2,3-DHBA,and lactate dehydrogenase.Conclusion:Melatonin may improve the outcome of heatstroke in rats by attenuating acute lung inflammation and injury.

  12. A Rathke's Cleft Cyst with Chronic Inflammation Mimicking a Pituitary Macroadenoma

    Energy Technology Data Exchange (ETDEWEB)

    Choo, Ka Yeon; Choi, Hyun Seok; Jung, So Lyung; Kim, Bum Soo; Ahn, Kook In [Dept. of Radiology, Seoul St.Mary' s Hospital, The Catholic University of Korea College of Medicine, Seoul (Korea, Republic of); Jeon, Shin Soo; Hong, Yong Kil [Dept. of Neurosurgery, Seoul St.Mary' s Hospital, The Catholic University of Korea College of Medicine, Seoul (Korea, Republic of)

    2011-11-15

    Rathke's cleft cyst is a benign cystic lesion arising in the sellar or suprasellar region. Most cases of Rathke's cleft cysts are thin-walled cystic lesions, but in rare cases, can cause a pituitary abscess by inflammation or infection. We report on a case of Rathke's cleft cyst with chronic inflammation mimicking a pituitary macroadenoma seen as a thick-walled irregular cystic lesion on brain CT and MRI.

  13. Inhibitors of inflammation and endogenous surfactant pool size as modulators of lung injury with initiation of ventilation in preterm sheep

    OpenAIRE

    Polglase Graeme R; Nitsos Ilias; Pillow J Jane; Kallapur Suhas G; Hillman Noah H; Ikegami Machiko; Jobe Alan H

    2010-01-01

    Abstract Background Increased pro-inflammatory cytokines in tracheal aspirates correlate with the development of BPD in preterm infants. Ventilation of preterm lambs increases pro-inflammatory cytokines and causes lung inflammation. Objective We tested the hypothesis that selective inhibitors of pro-inflammatory signaling would decrease lung inflammation induced by ventilation in preterm newborn lambs. We also examined if the variability in injury response was explained by variations in the e...

  14. One in vitro model for visceral adipose-derived fibroblasts in chronic inflammation

    International Nuclear Information System (INIS)

    One pathogenesis of the obesity-associated complications is that consistent with increased body fat mass, the elevation of adipose tissue-derived cytokines inflicts a low-grade chronic inflammation, which ultimately leads to metabolic disorders. Adipocytes and macrophages in visceral adipose (VA) have been confirmed to contribute to the chronic inflammation; however, the role of the resident fibroblasts is still unknown. We established one VA fibroblast cell line, termed VAFC. Morphological analysis indicated that there were large numbers of pits at the cell plasma membrane. In vitro VAFC cells promoted bone marrow cells to differentiate into macrophages and protected them from apoptosis in the serum-free conditions. Additionally, they also interfered in lymphocytes proliferation. On the basis of these results, this cell line might be an in vitro model for understanding the role of adipose-derived fibroblasts in obesity-associated chronic inflammation

  15. Emphysema is associated with increased inflammation in lungs of atherosclerosis-prone mice by cigarette smoke: implications in comorbidities of COPD

    Directory of Open Access Journals (Sweden)

    Yao Hongwei

    2010-07-01

    Full Text Available Abstract Background Chronic obstructive pulmonary disease is associated with numerous vascular effects including endothelial dysfunction, arterial stiffness and atherogenesis. It is also known that a decline in lung function is associated with increased cardiovascular comorbidity in smokers. The mechanism of this cardiopulmonary dual risk by cigarette smoke (CS is not known. We studied the molecular mechanisms involved in development of emphysema in atherosclerosis-prone apolipoprotein E-deficient (ApoE-/- mice in response to CS exposure. Methods Adult male and female wild-type (WT mice of genetic background C57BL/6J and ApoE-/- mice were exposed to CS, and lung inflammatory responses, oxidative stress (lipid peroxidation products, mechanical properties as well as airspace enlargement were assessed. Results and Discussion The lungs of ApoE-/- mice showed augmented inflammatory response and increased oxidative stress with development of distal airspace enlargement which was accompanied with decline in lung function. Interestingly, the levels and activities of matrix metalloproteinases (MMP-9 and MMP-12 were increased, whereas the level of eNOS was decreased in lungs of CS-exposed ApoE-/- mice as compared to air-exposed ApoE-/- mice or CS-exposed WT mice. Conclusion These findings suggest that CS causes premature emphysema and a decline of lung function in mice susceptible to cardiovascular abnormalities via abnormal lung inflammation, increased oxidative stress and alterations in levels of MMPs and eNOS.

  16. Chronic Pseudomonas aeruginosa lung infection in normal and athymic rats

    DEFF Research Database (Denmark)

    Johansen, H K; Espersen, F; Pedersen, S S;

    1993-01-01

    We have compared a chronic lung infection with Pseudomonas aeruginosa embedded in alginate beads in normal and athymic rats with an acute infection with free live P. aeruginosa bacteria. The following parameters were observed and described: mortality, macroscopic and microscopic pathologic changes......, and antibody responses. The rats challenged with P. aeruginosa alginate beads experienced a generally more severe lung pathology and the antibody responses were more homogeneous with less dispersion as compared to the rats having free live P. aeruginosa bacteria. In general, manifestations were more severe...... in the athymic rats compared to the normal rats. It is, however, notable that the athymic rats developed similar microscopic lung manifestations as the normal rats when given a large number of P. aeruginosa in the beads, with dense accumulation of neutrophil granulocytes and microcolonies comparable...

  17. Pulmonary rehabilitation improves sleep quality in chronic lung disease.

    Science.gov (United States)

    Soler, Xavier; Diaz-Piedra, Carolina; Ries, Andrew L

    2013-04-01

    Sleep-related disorders are common in patients with chronic obstructive pulmonary disease (COPD) and, possibily, other lung disorders. Exercise has been shown to improve sleep disturbances. In patients with COPD, pulmonary rehabilitation (PR) produces important health benefits with improvement in symptoms, exercise tolerance, and quality of life. However, the effect of PR on sleep quality remains unknown. The aim of this observational study was to evaluate sleep quality in patients with chronic lung disease and the role of PR as a non-pharmacologic treatment to improve sleep. Sixty-four patients with chronic lung disease enrolled in an 8-week comprehensive PR program, and completed the study (48% male; obstructive [72%], restrictive [20%], mixed [8%]; 44% on supplemental oxygen). Baseline spirometry [mean (SD)]: FEV1% pred = 48.9 (17.4), FVC% pred = 72.5 (18.1), and FEV1/FVC% = 53.1 (18.9). Exercise tolerance and questionnaires related to symptoms, health-related quality of life (HRQL), and sleep quality using the Pittsburgh Sleep Quality Index (PSQI) were obtained before and after PR. 58% reported poor sleep quality (PSQI > 5) at baseline. Sleep quality improved by 19% (p = 0.017) after PR, along with significant improvements in dyspnea, exercise tolerance, self-efficacy, and HRQL. Sleep quality in patients with chronic lung disease was poor. In addition to expected improvements in symptoms, exercise tolerance, and HRQL after PR, the subgroup of patients with COPD had a significant improvement in sleep quality. These findings suggest that PR may be an effective, non-pharmacologic treatment option for sleep problems in patients with COPD. PMID:23514215

  18. Effect of smoking cessation on airway inflammation of rats with chronic bronchitis

    Institute of Scientific and Technical Information of China (English)

    LI Qing-yun; HUANG Shao-guang; WAN Huan-ying; WU Hua-cheng; ZHOU Tong; LI Min; DENG Wei-wu

    2007-01-01

    Background Smoking is the major cause of airway inflammation in chronic obstructive pulmonary disease (COPD),and smoking cessation is regarded as one of the important strategies for prevention and treatment of the inflammation.The inflammation of the chronic airway may be present and deteriorated even if the COPD patients stop smoking.Whether and how early smoking cessation affects the progress of inflammation is still obscure. This study was conducted to find the appropriate time for smoking cessation to terminate the airway inflammation in rats with smoke-induced chronic bronchitis.Methods A rat model of COPD was established by passively inhaling smoke mixture. Fifty-four young male Sprague-Dawley rats were randomly divided into 9 groups with different periods of smoke exposure and different time points of cessation. The inflammation markers to be detected included inflammatory cells in the bronchoalveolar lavage fluid (BALF), the myeloperoxidose (MPO) activity, the morphologic changes and the expression of ICAM-1 on the airway epithelium.Results When smoking was terminated at early stage, the inflammatory markers and related indexes were different from those of the typical chronic bronchitis group (group M7) (P<0.01). The pathologic score of group SC7 (2 weeks of smoking cessation after occurrence of typical chronic bronchitis ) was not different from that of group M7, and the level of ICAM-1 was still up-regulated (compared to group M7, P>0.05). Meanwhile, most of inflammatory cells in BALF were neutrophils compared to other groups (P<0.01).When smoking was terminated, the MPO activity was significantly lower than that of group M7 (P<0.01).Conclusions Smoking cessation at early stage can effectively inhibit the inflammatory reaction of COPD. Once chronic bronchitis occurs, little could be improved by smoking cessation.

  19. Treatment with the Hyaluronic Acid Synthesis Inhibitor 4-Methylumbelliferone Suppresses SEB-Induced Lung Inflammation

    Directory of Open Access Journals (Sweden)

    Olga N. Uchakina

    2013-10-01

    Full Text Available Exposure to bacterial superantigens, such as staphylococcal enterotoxin B (SEB, can lead to the induction of acute lung injury/acute respiratory distress syndrome (ALI/ARDS. To date, there are no known effective treatments for SEB-induced inflammation. In the current study we investigated the potential use of the hyaluronic acid synthase inhibitor 4-methylumbelliferone (4-MU on staphylococcal enterotoxin B (SEB induced acute lung inflammation. Culturing SEB-activated immune cells with 4-MU led to reduced proliferation, reduced cytokine production as well as an increase in apoptosis when compared to untreated cells. Treatment of mice with 4-MU led to protection from SEB-induced lung injury. Specifically, 4-MU treatment led to a reduction in SEB-induced HA levels, reduction in lung permeability, and reduced pro-inflammatory cytokine production. Taken together, these results suggest that use of 4-MU to target hyaluronic acid production may be an effective treatment for the inflammatory response following exposure to SEB.

  20. Linalool attenuates lung inflammation induced by Pasteurella multocida via activating Nrf-2 signaling pathway.

    Science.gov (United States)

    Wu, Qianchao; Yu, Lijun; Qiu, Jiaming; Shen, Bingyu; Wang, Di; Soromou, Lanan Wassy; Feng, Haihua

    2014-08-01

    Pasteurellosis caused by Pasteurella multocida manifest often as respiratory infection in farmed small ruminants. Although the incidence of pasteurellosis due to P. multocida mainly takes the form of pneumonia, there is limited information on host factors that play a role in disease pathogenesis in the milieu of host-pathogen interactions. Nuclear factor-erythroid 2 related factor 2 (Nrf-2), a critical regulator for various inflammatory and immune responses by controlling oxidative stress, may play an important role in the processes of inflammation induced by P. multocida. In this study, linalool, a natural compound of the essential oils in several aromatic plant species, elevated nuclear Nrf-2 protein translocation in the A549 lung cell line and in vivo. The P. multocida-induced pro-inflammatory cytokines expression was abrogated by Nrf-2 siRNA. Postponed treatment with linalool decreased lung neutrophil accumulation and enhanced clearance of P. multocida. Furthermore, linalool significantly increased the expression of antioxidant enzymes regulated by Nrf-2 and diminished lung tissue levels of several pro-inflammatory cytokines, including tumor necrosis factor α (TNF-α) and interleukin (IL)-6. In addition, animals treated with linalool had a marked improvement in survival. These findings have uncovered that linalool acts as a novel Nrf-2 activator for a novel therapeutic strategy in pathogen-mediated lung inflammation.

  1. Treatment with the hyaluronic Acid synthesis inhibitor 4-methylumbelliferone suppresses LPS-induced lung inflammation.

    Science.gov (United States)

    McKallip, Robert J; Ban, Hao; Uchakina, Olga N

    2015-01-01

    Exposure to bacterial endotoxins, such as lipopolysaccharide (LPS), can lead to the induction of acute lung injury/acute respiratory distress syndrome (ALI/ARDS). To date, there are no known effective treatments for LPS-induced inflammation. In the current study, we investigated the potential use of the hyaluronic acid (HA) synthesis inhibitor 4-methylumbelliferone (4-MU) on LPS-induced acute lung inflammation. Culturing LPS-activated immune cells with 4-MU led to reduced proliferation, reduced cytokine production, and an increase in apoptosis when compared to untreated cells. Treatment of mice with 4-MU led to protection from LPS-induced lung injury. Specifically, 4-MU treatment led to a reduction in LPS-induced hyaluronic acid synthase (HAS) messenger RNA (mRNA) levels, reduction in lung permeability, and reduction in proinflammatory cytokine production. Taken together, these results suggest that use of 4-MU to target HA production may be an effective treatment for the inflammatory response following exposure to LPS.

  2. Systemic Inflammation and Lung Function Impairment in Morbidly Obese Subjects with the Metabolic Syndrome

    Directory of Open Access Journals (Sweden)

    Astrid van Huisstede

    2013-01-01

    Full Text Available Background. Obesity and asthma are associated. There is a relationship between lung function impairment and the metabolic syndrome. Whether this relationship also exists in the morbidly obese patients is still unknown. Hypothesis. Low-grade systemic inflammation associated with the metabolic syndrome causes inflammation in the lungs and, hence, lung function impairment. Methods. This is cross-sectional study of morbidly obese patients undergoing preoperative screening for bariatric surgery. Metabolic syndrome was assessed according to the revised NCEP-ATP III criteria. Results. A total of 452 patients were included. Patients with the metabolic syndrome (n=293 had significantly higher blood monocyte (mean 5.3 versus 4.9, P=0.044 and eosinophil percentages (median 1.0 versus 0.8, P=0.002, while the total leukocyte count did not differ between the groups. The FEV1/FVC ratio was significantly lower in patients with the metabolic syndrome (76.7% versus 78.2%, P=0.032. Blood eosinophils were associated with FEV1/FVC ratio (adj. B −0.113, P=0.018. Conclusion. Although the difference in FEV1/FVC ratio between the groups is relatively small, in this cross-sectional study, and its clinical relevance may be limited, these data indicate that the presence of the metabolic syndrome may influence lung function impairment, through the induction of relative eosinophilia.

  3. Neutrophilic airways inflammation in lung cancer: the role of exhaled LTB-4 and IL-8

    Directory of Open Access Journals (Sweden)

    Orlando Silvio

    2011-06-01

    Full Text Available Abstract Background Recent advances in lung cancer biology presuppose its inflammatory origin. In this regard, LTB-4 and IL-8 are recognized to play a crucial role in neutrophil recruitment into airways during lung cancer. Notwithstanding the intriguing hypothesis, the exact role of neutrophilic inflammation in tumour biology remains complex and not completely known. The aim of this study was to give our contribution in this field by investigating LTB-4 and IL-8 in the breath condensate of NSCLC patients and verifying their role in cancer development and progression. Method We enrolled 50 NSCLC patients and 35 controls. LTB-4 and IL-8 concentrations were measured in the breath condensate and the blood of all the subjects under study using EIA kits. Thirty NSCLC patients and ten controls underwent induced sputum collection and analysis. Results LTB-4 and IL-8 resulted higher in breath condensate and the blood of NSCLC patients compared to controls. Significantly higher concentrations were found as the cancer stages progressed. A positive correlation was observed between exhaled IL-8 and LTB-4 and the percentage of neutrophils in the induced sputum. Conclusion The high concentrations of exhaled LTB-4 and IL-8 showed the presence of a neutrophilic inflammation in the airways of NSCLC patients and gave a further support to the inflammatory signalling in lung cancer. These exhaled proteins could represent a suitable non-invasive marker in the diagnosis and monitoring of lung cancer.

  4. Inflammation, aging, and cancer: tumoricidal versus tumorigenesis of immunity: a common denominator mapping chronic diseases.

    Science.gov (United States)

    Khatami, Mahin

    2009-01-01

    Acute inflammation is a highly regulated defense mechanism of immune system possessing two well-balanced and biologically opposing arms termed apoptosis ('Yin') and wound healing ('Yang') processes. Unresolved or chronic inflammation (oxidative stress) is perhaps the loss of balance between 'Yin' and 'Yang' that would induce co-expression of exaggerated or 'mismatched' apoptotic and wound healing factors in the microenvironment of tissues ('immune meltdown'). Unresolved inflammation could initiate the genesis of many age-associated chronic illnesses such as autoimmune and neurodegenerative diseases or tumors/cancers. In this perspective 'birds' eye' view of major interrelated co-morbidity risk factors that participate in biological shifts of growth-arresting ('tumoricidal') or growth-promoting ('tumorigenic') properties of immune cells and the genesis of chronic inflammatory diseases and cancer will be discussed. Persistent inflammation is perhaps a common denominator in the genesis of nearly all age-associated health problems or cancer. Future challenging opportunities for diagnosis, prevention, and/or therapy of chronic illnesses will require an integrated understanding and identification of developmental phases of inflammation-induced immune dysfunction and age-associated hormonal and physiological readjustments of organ systems. Designing suitable cohort studies to establish the oxido-redox status of adults may prove to be an effective strategy in assessing individual's health toward developing personal medicine for healthy aging.

  5. High mobility group box 1 protein as a late-acting mediator of acute lung inflammation.

    Science.gov (United States)

    Lutz, Waldemar; Stetkiewicz, Jan

    2004-01-01

    Acute inflammatory lung injury is often a delayed complication of critical illness and is associated with increased mortality. High mobility group box 1 (HMGB1) protein, in addition to its role as a transcriptional regulator factor, has been identified as a late mediator of endotoxin lethality and might be also involved in the development and progression of acute lung injury. HMGB1 protein itself can cause an acute inflammatory response manifested by increased production of proinflammatory cytokines and neutrophil accumulation. The delayed kinetics of HMGB1 protein release indicate that this protein is a distal mediator of acute inflamatory lung injury. Anti-HMGB1 protein antibodies attenuated endotoxin-induced lung injury, but not the early release of TNF-alpha and IL-1beta, indicating that HMGB1 protein is a late mediator of endotoxin-induced acute lung injury. HMGB1 protein is not released by apoptotic cells but is passively released by necrotic or damaged somatic and immune cells and it functions as a major stimulus of necrosis-induced inflammation. HMGB1 protein is also released by activated monocytes/macrophages and induces delayed and biphasic release of proinflammatory mediators from these cells. HMGB1 protein failed to stimulate cytokines release in lymphocytes, indicating that cellular stimulation is specific. We would like to suggest that HMGB1 protein may be also a primary mediator of the inflammatory responses to lung cells injury caused by toxic environmental chemicals.

  6. Lung inflammation and immunity: report from the 12th ERS Lung Science Conference

    OpenAIRE

    Bruno Crestani; Marina Pretolani; Hamida Hammad

    2014-01-01

    The European Respiratory Society (ERS) seeks to alleviate suffering from respiratory diseases and promote lung health through research, dissemination of knowledge, and medical and public education. In support of this mission, the ERS organises the annual Lung Science Conference (LSC). This world-class research meeting brings together leading experts on topics that are of relevance to respiratory medicine. Furthermore, at the LSC, one of the main focuses is early-career physicians and scientis...

  7. FcgammaRIIb inhibits allergic lung inflammation in a murine model of allergic asthma.

    Directory of Open Access Journals (Sweden)

    Nilesh Dharajiya

    Full Text Available Allergic asthma is characterized by airway eosinophilia, increased mucin production and allergen-specific IgE. Fc gamma receptor IIb (FcgammaRIIb, an inhibitory IgG receptor, has recently emerged as a negative regulator of allergic diseases like anaphylaxis and allergic rhinitis. However, no studies to date have evaluated its role in allergic asthma. Our main objective was to study the role of FcgammaRIIb in allergic lung inflammation. We used a murine model of allergic airway inflammation. Inflammation was quantified by BAL inflammatory cells and airway mucin production. FcgammaRIIb expression was measured by qPCR and flow cytometry and the cytokines were quantified by ELISA. Compared to wild type animals, FcgammaRIIb deficient mice mount a vigorous allergic lung inflammation characterized by increased bronchoalveolar lavage fluid cellularity, eosinophilia and mucin content upon ragweed extract (RWE challenge. RWE challenge in sensitized mice upregulated FcgammaRIIb in the lungs. Disruption of IFN-gamma gene abrogated this upregulation. Treatment of naïve mice with the Th1-inducing agent CpG DNA increased FcgammaRIIb expression in the lungs. Furthermore, treatment of sensitized mice with CpG DNA prior to RWE challenge induced greater upregulation of FcgammaRIIb than RWE challenge alone. These observations indicated that RWE challenge upregulated FcgammaRIIb in the lungs by IFN-gamma- and Th1-dependent mechanisms. RWE challenge upregulated FcgammaRIIb on pulmonary CD14+/MHC II+ mononuclear cells and CD11c+ cells. FcgammaRIIb deficient mice also exhibited an exaggerated RWE-specific IgE response upon sensitization when compared to wild type mice. We propose that FcgammaRIIb physiologically regulates allergic airway inflammation by two mechanisms: 1 allergen challenge mediates upregulation of FcgammaRIIb on pulmonary CD14+/MHC II+ mononuclear cells and CD11c+ cells by an IFN-gamma dependent mechanism; and 2 by attenuating the allergen specific Ig

  8. Chronic Inflammation in Obesity and the Metabolic Syndrome

    Directory of Open Access Journals (Sweden)

    Rosário Monteiro

    2010-01-01

    Full Text Available The increasing incidence of obesity and the metabolic syndrome is disturbing. The activation of inflammatory pathways, used normally as host defence, reminds the seriousness of this condition. There is probably more than one cause for activation of inflammation. Apparently, metabolic overload evokes stress reactions, such as oxidative, inflammatory, organelle and cell hypertrophy, generating vicious cycles. Adipocyte hypertrophy, through physical reasons, facilitates cell rupture, what will evoke an inflammatory reaction. Inability of adipose tissue development to engulf incoming fat leads to deposition in other organs, mainly in the liver, with consequences on insulin resistance. The oxidative stress which accompanies feeding, particularly when there is excessive ingestion of fat and/or other macronutrients without concomitant ingestion of antioxidant-rich foods/beverages, may contribute to inflammation attributed to obesity. Moreover, data on the interaction of microbiota with food and obesity brought new hypothesis for the obesity/fat diet relationship with inflammation. Beyond these, other phenomena, for instance psychological and/or circadian rhythm disturbances, may likewise contribute to oxidative/inflammatory status. The difficulty in the management of obesity/metabolic syndrome is linked to their multifactorial nature where environmental, genetic and psychosocial factors interact through complex networks.

  9. Surfactant dysfunction and lung inflammation in the female mouse model of lymphangioleiomyomatosis.

    Science.gov (United States)

    Atochina-Vasserman, Elena N; Guo, Chang-Jiang; Abramova, Elena; Golden, Thea N; Sims, Michael; James, Melane L; Beers, Michael F; Gow, Andrew J; Krymskaya, Vera P

    2015-07-01

    Pulmonary lymphangioleiomyomatosis (LAM) is a rare lung disease caused by mutations of the tumor suppressor genes, tuberous sclerosis complex (TSC) 1 or TSC2. LAM affects women almost exclusively, and it is characterized by neoplastic growth of atypical smooth muscle-like TSC2-null LAM cells in the pulmonary interstitium, cystic destruction of lung parenchyma, and progressive decline in lung function. In this study, we hypothesized that TSC2-null lesions promote a proinflammatory environment, which contributes to lung parenchyma destruction. Using a TSC2-null female murine LAM model, we demonstrate that TSC2-null lesions promote alveolar macrophage accumulation, recruitment of immature multinucleated cells, an increased induction of proinflammatory genes, nitric oxide (NO) synthase 2, IL-6, chemokine (C-C motif) ligand 2 (CCL2)/monocyte chemotactic protein 1 (MCP1), chemokine (C-X-C motif) ligand 1 (CXCL1)/keratinocyte chemoattractant (KC), and up-regulation of IL-6, KC, MCP-1, and transforming growth factor-β1 levels in bronchoalveolar lavage fluid. Bronchoalveolar lavage fluid also contained an increased level of surfactant protein (SP)-D, but not SP-A, significant reduction of SP-B levels, and a resultant increase in alveolar surface tension. Consistent with the growth of TSC2-null lesions, NO levels were also increased and, in turn, modified SP-D through S-nitrosylation, forming S-nitrosylated SP-D, a known consequence of lung inflammation. Progressive growth of TSC2-null lesions was accompanied by elevated levels of matrix metalloproteinase-3 and -9. This report demonstrates a link between growth of TSC2-null lesions and inflammation-induced surfactant dysfunction that might contribute to lung destruction in LAM. PMID:25474372

  10. Low-grade inflammation in chronic diseases: an integrative pathophysiology anticipated by homeopathy?

    Science.gov (United States)

    Adler, Ubiratan Cardinalli

    2011-05-01

    Pro-inflammatory cytokines and their chronic effect - low-grade inflammation - have been associated with diverse chronic conditions. Nonsteroidal anti-inflammatory drugs (NSAIDs) were recently proposed as a treatment strategy. Samuel Hahnemann, the founder of homeopathy, had already hypothesized a systemic and progressive disorder as the cause of many chronic diseases - the Psora theory. He also advised of the consequences of palliative use for chronic diseases, as a contrary effect of the "of the life-preserving principle" could worsen the course of those diseases. The hypotheses presented here are that the main aspects of Hahnemann's Psora theory are supported by current data on the role of pro-inflammatory cytokines and that the use of NSAIDs to treat chronic low-grade inflammation can produce a contrary, rebound effect, as anticipated by Hahnemann. By diverting from the "palliative action-rebound effect" course, not only homeopathy but integrative medicine could provide different approaches to the treatment of low-grade chronic inflammation. Studies assessing inflammatory markers in chronic integrative treatments are recommended. PMID:21277692

  11. Liver stiffness measurement-based scoring system for significant inflammation related to chronic hepatitis B.

    Directory of Open Access Journals (Sweden)

    Mei-Zhu Hong

    Full Text Available Liver biopsy is indispensable because liver stiffness measurement alone cannot provide information on intrahepatic inflammation. However, the presence of fibrosis highly correlates with inflammation. We constructed a noninvasive model to determine significant inflammation in chronic hepatitis B patients by using liver stiffness measurement and serum markers.The training set included chronic hepatitis B patients (n = 327, and the validation set included 106 patients; liver biopsies were performed, liver histology was scored, and serum markers were investigated. All patients underwent liver stiffness measurement.An inflammation activity scoring system for significant inflammation was constructed. In the training set, the area under the curve, sensitivity, and specificity of the fibrosis-based activity score were 0.964, 91.9%, and 90.8% in the HBeAg(+ patients and 0.978, 85.0%, and 94.0% in the HBeAg(- patients, respectively. In the validation set, the area under the curve, sensitivity, and specificity of the fibrosis-based activity score were 0.971, 90.5%, and 92.5% in the HBeAg(+ patients and 0.977, 95.2%, and 95.8% in the HBeAg(- patients. The liver stiffness measurement-based activity score was comparable to that of the fibrosis-based activity score in both HBeAg(+ and HBeAg(- patients for recognizing significant inflammation (G ≥3.Significant inflammation can be accurately predicted by this novel method. The liver stiffness measurement-based scoring system can be used without the aid of computers and provides a noninvasive alternative for the prediction of chronic hepatitis B-related significant inflammation.

  12. Liver Stiffness Measurement-Based Scoring System for Significant Inflammation Related to Chronic Hepatitis B

    Science.gov (United States)

    Hong, Mei-Zhu; Zhang, Ru-Mian; Chen, Guo-Liang; Huang, Wen-Qi; Min, Feng; Chen, Tian; Xu, Jin-Chao; Pan, Jin-Shui

    2014-01-01

    Objectives Liver biopsy is indispensable because liver stiffness measurement alone cannot provide information on intrahepatic inflammation. However, the presence of fibrosis highly correlates with inflammation. We constructed a noninvasive model to determine significant inflammation in chronic hepatitis B patients by using liver stiffness measurement and serum markers. Methods The training set included chronic hepatitis B patients (n = 327), and the validation set included 106 patients; liver biopsies were performed, liver histology was scored, and serum markers were investigated. All patients underwent liver stiffness measurement. Results An inflammation activity scoring system for significant inflammation was constructed. In the training set, the area under the curve, sensitivity, and specificity of the fibrosis-based activity score were 0.964, 91.9%, and 90.8% in the HBeAg(+) patients and 0.978, 85.0%, and 94.0% in the HBeAg(−) patients, respectively. In the validation set, the area under the curve, sensitivity, and specificity of the fibrosis-based activity score were 0.971, 90.5%, and 92.5% in the HBeAg(+) patients and 0.977, 95.2%, and 95.8% in the HBeAg(−) patients. The liver stiffness measurement-based activity score was comparable to that of the fibrosis-based activity score in both HBeAg(+) and HBeAg(−) patients for recognizing significant inflammation (G ≥3). Conclusions Significant inflammation can be accurately predicted by this novel method. The liver stiffness measurement-based scoring system can be used without the aid of computers and provides a noninvasive alternative for the prediction of chronic hepatitis B-related significant inflammation. PMID:25360742

  13. Cerium oxide nanoparticles protect rodent lungs from hypobaric hypoxia-induced oxidative stress and inflammation

    Directory of Open Access Journals (Sweden)

    Arya A

    2013-11-01

    intraperitoneal injections of low micromole concentration, we successfully localized the nanoceria in rodent lung without any inflammatory response. The lung-deposited nanoceria limited ROS formation, lipid peroxidation, and glutathione oxidation, and prevented oxidative protein modifications like nitration and carbonyl formation during hypobaric hypoxia. We also observed reduced lung inflammation in the nanoceria-injected lungs, supporting the anti-inflammatory properties of nanoceria. Conclusion: Cumulatively, these results suggest nanoceria deposit in lungs, confer protection by quenching noxious free radicals during hypobaric hypoxia, and do not evoke any inflammatory response. Keywords: nanoceria, high altitude, nanomedicine

  14. Allergic lung inflammation alters neither susceptibility to Streptococcus pneumoniae infection nor inducibility of innate resistance in mice

    Directory of Open Access Journals (Sweden)

    Evans Christopher M

    2009-07-01

    Full Text Available Abstract Background Protective host responses to respiratory pathogens are typically characterized by inflammation. However, lung inflammation is not always protective and it may even become deleterious to the host. We have recently reported substantial protection against Streptococcus pneumoniae (pneumococcal pneumonia by induction of a robust inflammatory innate immune response to an inhaled bacterial lysate. Conversely, the allergic inflammation associated with asthma has been proposed to promote susceptibility to pneumococcal disease. This study sought to determine whether preexisting allergic lung inflammation influences the progression of pneumococcal pneumonia or reduces the inducibilty of protective innate immunity against bacteria. Methods To compare the effect of different inflammatory and secretory stimuli on defense against pneumonia, intraperitoneally ovalbumin-sensitized mice were challenged with inhaled pneumococci following exposure to various inhaled combinations of ovalbumin, ATP, and/or a bacterial lysate. Thus, allergic inflammation, mucin degranulation and/or stimulated innate resistance were induced prior to the infectious challenge. Pathogen killing was evaluated by assessing bacterial CFUs of lung homogenates immediately after infection, the inflammatory response to the different conditions was evaluated by measurement of cell counts of bronchoalveolar lavage fluid 18 hours after challenge, and mouse survival was assessed after seven days. Results We found no differences in survival of mice with and without allergic inflammation, nor did the induction of mucin degranulation alter survival. As we have found previously, mice treated with the bacterial lysate demonstrated substantially increased survival at seven days, and this was not altered by the presence of allergic inflammation or mucin degranulation. Allergic inflammation was associated with predominantly eosinophilic infiltration, whereas the lysate-induced response

  15. Current concepts on oxidative/carbonyl stress, inflammation and epigenetics in pathogenesis of chronic obstructive pulmonary disease

    International Nuclear Information System (INIS)

    Chronic obstructive pulmonary disease (COPD) is a global health problem. The current therapies for COPD are poorly effective and the mainstays of pharmacotherapy are bronchodilators. A better understanding of the pathobiology of COPD is critical for the development of novel therapies. In the present review, we have discussed the roles of oxidative/aldehyde stress, inflammation/immunity, and chromatin remodeling in the pathogenesis of COPD. An imbalance of oxidants/antioxidants caused by cigarette smoke and other pollutants/biomass fuels plays an important role in the pathogenesis of COPD by regulating redox-sensitive transcription factors (e.g., NF-κB), autophagy and unfolded protein response leading to chronic lung inflammatory response. Cigarette smoke also activates canonical/alternative NF-κB pathways and their upstream kinases leading to sustained inflammatory response in lungs. Recently, epigenetic regulation has been shown to be critical for the development of COPD because the expression/activity of enzymes that regulate these epigenetic modifications have been reported to be abnormal in airways of COPD patients. Hence, the significant advances made in understanding the pathophysiology of COPD as described herein will identify novel therapeutic targets for intervention in COPD.

  16. Chronic Exposure to Beta-Blockers Attenuates Inflammation and Mucin Content in a Murine Asthma Model

    OpenAIRE

    Nguyen, Long P.; Omoluabi, Ozozoma; Parra, Sergio; Frieske, Joanna M.; Clement, Cecilia; Ammar-Aouchiche, Zoulikha; Ho, Samuel B.; Ehre, Camille; Kesimer, Mehmet; Knoll, Brian J.; Tuvim, Michael J; Dickey, Burton F.; Bond, Richard A.

    2007-01-01

    Single-dose administration of beta-adrenoceptor agonists produces bronchodilation and inhibits airway hyperresponsiveness (AHR), and is the standard treatment for the acute relief of asthma. However, chronic repetitive administration of beta-adrenoceptor agonists may increase AHR, airway inflammation, and risk of death. Based upon the paradigm shift that occurred with the use of beta-blockers in congestive heart failure, we previously determined that chronic administration of beta-blockers de...

  17. Disruption of Sirtuin 1-Mediated Control of Circadian Molecular Clock and Inflammation in Chronic Obstructive Pulmonary Disease.

    Science.gov (United States)

    Yao, Hongwei; Sundar, Isaac K; Huang, Yadi; Gerloff, Janice; Sellix, Michael T; Sime, Patricia J; Rahman, Irfan

    2015-12-01

    Chronic obstructive pulmonary disease (COPD) is the fourth most common cause of death, and it is characterized by abnormal inflammation and lung function decline. Although the circadian molecular clock regulates inflammatory responses, there is no information available regarding the impact of COPD on lung molecular clock function and its regulation by sirtuin 1 (SIRT1). We hypothesize that the molecular clock in the lungs is disrupted, leading to increased inflammatory responses in smokers and patients with COPD and its regulation by SIRT1. Lung tissues, peripheral blood mononuclear cells (PBMCs), and sputum cells were obtained from nonsmokers, smokers, and patients with COPD for measurement of core molecular clock proteins (BMAL1, CLOCK, PER1, PER2, and CRY1), clock-associated nuclear receptors (REV-ERBα, REV-ERBβ, and RORα), and SIRT1 by immunohistochemistry, immunofluorescence, and immunoblot. PBMCs were treated with the SIRT1 activator SRT1720 followed by LPS treatment, and supernatant was collected at 6-hour intervals. Levels of IL-8, IL-6, and TNF-α released from PBMCs were determined by ELISA. Expression of BMAL1, PER2, CRY1, and REV-ERBα was reduced in PBMCs, sputum cells, and lung tissues from smokers and patients with COPD when compared with nonsmokers. SRT1720 treatment attenuated LPS-mediated reduction of BMAL1 and REV-ERBα in PBMCs from nonsmokers. Additionally, LPS differentially affected the timing and amplitude of cytokine (IL-8, IL-6, and TNF-α) release from PBMCs in nonsmokers, smokers, and patients with COPD. Moreover, SRT1720 was able to inhibit LPS-induced cytokine release from cultured PBMCs. In conclusion, disruption of the molecular clock due to SIRT1 reduction contributes to abnormal inflammatory response in smokers and patients with COPD.

  18. Experimental chronic Pseudomonas aeruginosa lung infection in rats. Non-specific stimulation with LPS reduces lethality as efficiently as specific immunization

    DEFF Research Database (Denmark)

    Lange, K H; Hougen, H P; Høiby, N;

    1995-01-01

    In a rat model of chronic Pseudomonas aeruginosa lung infection mimicking cystic fibrosis, we investigated the possibility of preventing chronic lung inflammation or decreasing the progression of the infection. We compared the lethality, pathology, bacterial clearance, and immunogenicity after...... with either E. coli LPS or P. aeruginosa sonicate. Four and two weeks prior to challenge other rats were vaccinated with either E. coli LPS or P. aeruginosa sonicate. Controls did not receive any stimulation or vaccination. The lethality after challenge was lower in rats stimulated with E. coli LPS (p = 0...

  19. Interleukin-17 Pathophysiology and Therapeutic Intervention in Cystic Fibrosis Lung Infection and Inflammation.

    Science.gov (United States)

    Hsu, Daniel; Taylor, Patricia; Fletcher, Dave; van Heeckeren, Rolf; Eastman, Jean; van Heeckeren, Anna; Davis, Pamela; Chmiel, James F; Pearlman, Eric; Bonfield, Tracey L

    2016-09-01

    Cystic fibrosis (CF) is characterized by an excessive neutrophilic inflammatory response within the airway as a result of defective cystic fibrosis transmembrane receptor (CFTR) expression and function. Interleukin-17A induces airway neutrophilia and mucin production associated with Pseudomonas aeruginosa colonization, which is associated with the pathophysiology of cystic fibrosis. The objectives of this study were to use the preclinical murine model of cystic fibrosis lung infection and inflammation to investigate the role of IL-17 in CF lung pathophysiology and explore therapeutic intervention with a focus on IL-17. Cftr-deficient mice (CF mice) and wild-type mice (WT mice) infected with P. aeruginosa had robust IL-17 production early in the infection associated with a persistent elevated inflammatory response. Intratracheal administration of IL-17 provoked a neutrophilic response in the airways of WT and CF animals which was similar to that observed with P. aeruginosa infection. The neutralization of IL-17 prior to infection significantly improved the outcomes in the CF mice, suggesting that IL-17 may be a therapeutic target. We demonstrate in this report that the pathophysiological contribution of IL-17 may be due to the induction of chemokines from the epithelium which is augmented by a deficiency of Cftr and ongoing inflammation. These studies demonstrate the in vivo contribution of IL-17 in cystic fibrosis lung disease and the therapeutic validity of attenuating IL-17 activity in cystic fibrosis. PMID:27271746

  20. Angiogenesis : Potentials for pharmacologic intervention in the treatment of cancer, cardiovascular diseases, and chronic inflammation

    NARCIS (Netherlands)

    Griffioen, AW; Molema, G

    2000-01-01

    Angiogenesis, or the formation of new blood vessels out of pre-existing capillaries, is a sequence of events that is fundamental to many physiologic and pathologic processes such as cancer, ischemic diseases, and chronic inflammation. With the identification of several proangiogenic molecules such a

  1. Antioxidant Effect of Spirulina (Arthrospira) maxima on Chronic Inflammation Induced by Freund's Complete Adjuvant in Rats.

    Science.gov (United States)

    Gutiérrez-Rebolledo, Gabriel Alfonso; Galar-Martínez, Marcela; García-Rodríguez, Rosa Virginia; Chamorro-Cevallos, Germán A; Hernández-Reyes, Ana Gabriela; Martínez-Galero, Elizdath

    2015-08-01

    One of the major mechanisms in the pathogenesis of chronic inflammation is the excessive production of reactive oxygen and reactive nitrogen species, and therefore, oxidative stress. Spirulina (Arthrospira) maxima has marked antioxidant activity in vivo and in vitro, as well as anti-inflammatory activity in certain experimental models, the latter activity being mediated probably by the antioxidant activity of this cyanobacterium. In the present study, chronic inflammation was induced through injection of Freund's complete adjuvant (CFA) in rats treated daily with Spirulina (Arthrospira) maxima for 2 weeks beginning on day 14. Joint diameter, body temperature, and motor capacity were assessed each week. On days 0 and 28, total and differential leukocyte counts and serum oxidative damage were determined, the latter by assessing lipid peroxidation and protein carbonyl content. At the end of the study, oxidative damage to joints was likewise evaluated. Results show that S. maxima favors increased mobility, as well as body temperature regulation, and a number of circulating leukocytes, lymphocytes, and monocytes in specimens with CFA-induced chronic inflammation and also protects against oxidative damage in joint tissue as well as serum. In conclusion, the protection afforded by S. maxima against development of chronic inflammation is due to its antioxidant activity.

  2. Clinical Observation in 102 Cases of Chronic Pelvic Inflammation Treated with Qi Jie Granules

    Institute of Scientific and Technical Information of China (English)

    章勤; 何嘉琳; 何少山; 许萍

    2004-01-01

    Objective: To observe the therapeutic effects of Qi Jie Granule (芪竭颗粒) on chronic pelvic inflammation. Method: The therapeutic effect, T-lymphocytic subgroups and indexes of blood rheology were observed when 102 cases of chronic pelvic inflammation in the treatment group were treated with Qi Jie Granule, and another 70 cases were treated with Qian Jin Pian as the controls. Results: The total effective rate was 96.08% in the treatment group, but 84.29% in the control group with a significant difference between the two groups (P<0.01). Qi Jie Granule was also found effective in improving blood viscosity and regulating T-lymphocytic subgroups, and the difference before and after the treatment was also very significant (P<0.05 or P<0.01). Conclusion: The nature of chronic pelvic inflammation is qi deficiency and blood stasis in accordance with the theory of traditional Chinese medicine (TCM). As a drug that is indicated for chronic pelvic inflammation, its mechanism may be related to the improved blood circulation, accelerated inflammatory absorption and regulated immune function.

  3. CD28/B7 Deficiency Attenuates Systolic Overload-Induced Congestive Heart Failure, Myocardial and Pulmonary Inflammation, and Activated T Cell Accumulation in the Heart and Lungs.

    Science.gov (United States)

    Wang, Huan; Kwak, Dongmin; Fassett, John; Hou, Lei; Xu, Xin; Burbach, Brandon J; Thenappan, Thenappan; Xu, Yawei; Ge, Jun-Bo; Shimizu, Yoji; Bache, Robert J; Chen, Yingjie

    2016-09-01

    The inflammatory response regulates congestive heart failure (CHF) development. T cell activation plays an important role in tissue inflammation. We postulate that CD28 or B7 deficiency inhibits T cell activation and attenuates CHF development by reducing systemic, cardiac, and pulmonary inflammation. We demonstrated that chronic pressure overload-induced end-stage CHF in mice is characterized by profound accumulation of activated effector T cells (CD3(+)CD44(high) cells) in the lungs and a mild but significant increase of these cells in the heart. In knockout mice lacking either CD28 or B7, there was a dramatic reduction in the accumulation of activated effector T cells in both hearts and lungs of mice under control conditions and after transverse aortic constriction. CD28 or B7 knockout significantly attenuated transverse aortic constriction-induced CHF development, as indicated by less increase of heart and lung weight and less reduction of left ventricle contractility. CD28 or B7 knockout also significantly reduced transverse aortic constriction-induced CD45(+) leukocyte, T cell, and macrophage infiltration in hearts and lungs, lowered proinflammatory cytokine expression (such as tumor necrosis factor-α and interleukin-1β) in lungs. Furthermore, CD28/B7 blockade by CTLA4-Ig treatment (250 μg/mouse every 3 days) attenuated transverse aortic constriction-induced T cell activation, left ventricle hypertrophy, and left ventricle dysfunction. Our data indicate that CD28/B7 deficiency inhibits activated effector T cell accumulation, reduces myocardial and pulmonary inflammation, and attenuates the development of CHF. Our findings suggest that strategies targeting T cell activation may be useful in treating CHF.

  4. Pulmonary Hypertension and Right Heart Dysfunction in Chronic Lung Disease

    Directory of Open Access Journals (Sweden)

    Amirmasoud Zangiabadi

    2014-01-01

    Full Text Available Group 3 pulmonary hypertension (PH is a common complication of chronic lung disease (CLD, including chronic obstructive pulmonary disease (COPD, interstitial lung disease, and sleep-disordered breathing. Development of PH is associated with poor prognosis and may progress to right heart failure, however, in the majority of the patients with CLD, PH is mild to moderate and only a small number of patients develop severe PH. The pathophysiology of PH in CLD is multifactorial and includes hypoxic pulmonary vasoconstriction, pulmonary vascular remodeling, small vessel destruction, and fibrosis. The effects of PH on the right ventricle (RV range between early RV remodeling, hypertrophy, dilatation, and eventual failure with associated increased mortality. The golden standard for diagnosis of PH is right heart catheterization, however, evidence of PH can be appreciated on clinical examination, serology, radiological imaging, and Doppler echocardiography. Treatment of PH in CLD focuses on management of the underlying lung disorder and hypoxia. There is, however, limited evidence to suggest that PH-specific vasodilators such as phosphodiesterase-type 5 inhibitors, endothelin receptor antagonists, and prostanoids may have a role in the treatment of patients with CLD and moderate-to-severe PH.

  5. Sex influence on chronic intestinal inflammation in Helicobacter hepaticus-infected A/JCr mice.

    Science.gov (United States)

    Livingston, Robert S; Myles, Mathew H; Livingston, Beth A; Criley, Jennifer M; Franklin, Craig L

    2004-06-01

    Helicobacter hepaticus is a bacterial pathogen of mice that has been reported to cause chronic intestinal inflammation in A/JCr, germfree Swiss Webster, and immunodeficient mice. To the authors' knowledge, the influence of sex on development of chronic intestinal inflammation in H. hepaticus-infected mice has not been investigated. The purposes of the study reported here were to determine whether severity of intestinal inflammation differs between male and female A/JCr mice chronically infected with H. hepaticus and to characterize the mucosal immune response in these mice. The cecum of male and female A/JCr mice infected with H. hepaticus for 1 month and 3 months was objectively evaluated histologically for intestinal disease. Also, semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) analysis was done to measure interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha), interleukin 4 (IL-4), IL-10, macrophage inflammatory protein-1alpha (MIP-1alpha), interferon-inducible protein of 10 kDa (IP-10), and monokine induced by gamma interferon (MIG) mRNA values in the cecal tissue of these mice. Significant differences in cecal lesion scores were not present at 1 month after infection. However, infected female mice had significantly up-regulated expression of cecal IL-10, MIP-1alpha, IP-10, and MIG mRNA compared with that in uninfected females, and expression of IL-10 and MIP-1alpha was significantly greater than that detected in infected male mice (P JCr mice, females develop more severe intestinal inflammation than do males, and the chronic mucosal inflammation is polarized toward a Th1 response that is not down-regulated by increased activity of IL-10. We propose that H. hepaticus-infected A/JCr mice will serve as a good animal model with which to study the influence of sex on bacterial-induced mucosal inflammation.

  6. Pathogenic effects of biofilm with chronic pseudomonas aeruginosa lung infection in rats

    Institute of Scientific and Technical Information of China (English)

    Ping Yan; Yiqiang Chen; Zhijun Song; Hong Wu; Jinliang Kong; Xuejun Qin

    2008-01-01

    Objective: To establish an animal model of P.aeruginosa biofilm associated with chronic pulmonary infection and investigate the pathogenic effects of biofilm. Methods: Experiments in vitro, measuring the MICS, MBCS of ievofloxacin(LFX), ceftazidime(CAZ) in PAO579 in alginate beads and planktonic PAO579. Rats were challenged with 0.1 ml of PAO579(109CFU/ml) in alginate beads or 0.1 ml of planktonic PAO579(109CFU/ml), 3,7,14 days after challenging, bacteriological, pathological features were observed. Results: The MICS, MBCS of LFX, CAZ in PAO579 in alginate beads were higher than those in planktonic PAO579 in vitro. CFU/lung in alginate beads group was significantly higher than that in planktonic bacteria group(P = 0.002, P =0.004, P = 0.002, respectively); macroscopic lung pathology and the inflammation in alginate beads group were significantly more severe compared to those in planktonic bacteria group in vivo. Conclusion: P.aeruginosa biofilm protected bacterium from killing of antibiotics and might mediate the host immune damage in the lung tissue and made bacterium evade the host immune defense.

  7. Relationship between airway inflammation and remodeling in patients with asthma and chronic obstructive pulmonary disease

    Directory of Open Access Journals (Sweden)

    Górska K

    2009-12-01

    Full Text Available Abstract Despite a number of important differences in the pathogenesis, course and prognosis of asthma and chronic obstructive pulmonary disease (COPD, these two entities also have common features with airway inflammation being one of them. Airway remodeling is a characteristic feature of asthma, but data on the bronchial wall thickening in COPD patients are still scarce. Aim To assess the relation between the inflammatory cell count in the bronchoalveolar lavage fluid (BALF and thickness of bronchial walls assessed by high resolution computed tomography (HRCT in asthma and COPD patients. Material and methods The study was conducted in 9 patients with mild-to-moderate asthma (M/F 4/5, mean age 35 ± 10 years and 11 patients with mild-to-moderate COPD (M/F 7/4, mean age 57 ± 9 years. In all subjects lung function tests and HRCT scanning of the chest were performed. External (D and internal (L diameters of the airways were assessed at five selected lung levels. The lumen area (AL, wall area (WA, wall thickness (WT and bronchial wall thickness (WT/D ratio were calculated. Eight patients with asthma and 8 patients with COPD underwent fiberoptic bronchoscopy and bronchoalveolar lavage (BAL. Total and differential cell counts were assessed in the BAL fluid. Results Mean FEV1% pred was 80 ± 19%, and 73 ± 20% in asthma and COPD patients, respectively (NS. No significant differences in the total and differential cell counts in BALF were found in patients with asthma and COPD. There were no significant differences in the airway diameter or airway wall thickness. The mean inner airway diameter was 1.4 ± 0.3 and 1.2 ± 0.3 mm and the mean lumen area was 1.8 ± 0.7 and 1.6 ± 0.7 mm2 in asthma and COPD, respectively (NS. Negative correlations between the eosinophil count in BALF and inner airway diameter (r = -0.7, P Conclusions In mild-to-moderate asthma and COPD the airway diameter and thickness are similar. In asthmatics, the airway diameter might be

  8. Obesity-induced chronic inflammation in C57Bl6J mice, a novel risk factor in the progression of renal AA amyloidosis?

    NARCIS (Netherlands)

    Van Der Heijden, R.A.; Sheedfar, F.; Bijzet, J.; Hazenberg, B.P.; Koonen, D.P.; Heeringa, P.

    2015-01-01

    Background: Compelling evidence links obesity induced systemic inflammation to the development of chronic kidney disease (CKD). This systemic inflammation may result from exacerbated adipose inflammation. Besides the known detrimental effects of typical pro-inflammatory factors secreted by the adipo

  9. Angiopoietin-1 treatment reduces inflammation but does not prevent ventilator-induced lung injury.

    Directory of Open Access Journals (Sweden)

    Maria A Hegeman

    Full Text Available BACKGROUND: Loss of integrity of the epithelial and endothelial barriers is thought to be a prominent feature of ventilator-induced lung injury (VILI. Based on its function in vascular integrity, we hypothesize that the angiopoietin (Ang-Tie2 system plays a role in the development of VILI. The present study was designed to examine the effects of mechanical ventilation on the Ang-Tie2 system in lung tissue. Moreover, we evaluated whether treatment with Ang-1, a Tie2 receptor agonist, protects against inflammation, vascular leakage and impaired gas exchange induced by mechanical ventilation. METHODS: Mice were anesthetized, tracheotomized and mechanically ventilated for 5 hours with either an inspiratory pressure of 10 cmH2O ('low' tidal volume ∼7.5 ml/kg; LVT or 18 cmH2O ('high' tidal volume ∼15 ml/kg; HVT. At initiation of HVT-ventilation, recombinant human Ang-1 was intravenously administered (1 or 4 µg per animal. Non-ventilated mice served as controls. RESULTS: HVT-ventilation influenced the Ang-Tie2 system in lungs of healthy mice since Ang-1, Ang-2 and Tie2 mRNA were decreased. Treatment with Ang-1 increased Akt-phosphorylation indicating Tie2 signaling. Ang-1 treatment reduced infiltration of granulocytes and expression of keratinocyte-derived chemokine (KC, macrophage inflammatory protein (MIP-2, monocyte chemotactic protein (MCP-1 and interleukin (IL-1β caused by HVT-ventilation. Importantly, Ang-1 treatment did not prevent vascular leakage and impaired gas exchange in HVT-ventilated mice despite inhibition of inflammation, vascular endothelial growth factor (VEGF and Ang-2 expression. CONCLUSIONS: Ang-1 treatment downregulates pulmonary inflammation, VEGF and Ang-2 expression but does not protect against vascular leakage and impaired gas exchange induced by HVT-ventilation.

  10. Macrophage phenotype is associated with disease severity in preterm infants with chronic lung disease.

    Directory of Open Access Journals (Sweden)

    Lynne R Prince

    Full Text Available BACKGROUND: The etiology of persistent lung inflammation in preterm infants with chronic lung disease of prematurity (CLD is poorly characterized, hampering efforts to stratify prognosis and treatment. Airway macrophages are important innate immune cells with roles in both the induction and resolution of tissue inflammation. OBJECTIVES: To investigate airway innate immune cellular phenotypes in preterm infants with respiratory distress syndrome (RDS or CLD. METHODS: Bronchoalveolar lavage (BAL fluid was obtained from term and preterm infants requiring mechanical ventilation. BAL cells were phenotyped by flow cytometry. RESULTS: Preterm birth was associated with an increase in the proportion of non-classical CD14(+/CD16(+ monocytes on the day of delivery (58.9 ± 5.8% of total mononuclear cells in preterm vs 33.0 ± 6.1% in term infants, p = 0.02. Infants with RDS were born with significantly more CD36(+ macrophages compared with the CLD group (70.3 ± 5.3% in RDS vs 37.6 ± 8.9% in control, p = 0.02. At day 3, infants born at a low gestational age are more likely to have greater numbers of CD14(+ mononuclear phagocytes in the airway (p = 0.03, but fewer of these cells are functionally polarized as assessed by HLA-DR (p = 0.05 or CD36 (p = 0.05 positivity, suggesting increased recruitment of monocytes or a failure to mature these cells in the lung. CONCLUSIONS: These findings suggest that macrophage polarization may be affected by gestational maturity, that more immature macrophage phenotypes may be associated with the progression of RDS to CLD and that phenotyping mononuclear cells in BAL could predict disease outcome.

  11. Chronic inflammation as a promotor of mutagenesis in essential thrombocythemia, polycythemia vera and myelofibrosis. A human inflammation model for cancer development?

    DEFF Research Database (Denmark)

    Hasselbalch, Hans K

    2013-01-01

    The Philadelphia-negative chronic myeloproliferative neoplasms (MPNs) are acquired stem cell neoplasms, in which a stem cell lesion induces an autonomous proliferative advantage. In addition to the JAK2V617 mutation several other mutations have been described. Recently chronic inflammation has be...

  12. Effect of low tidal volume ventilation on lung function and inflammation in mice

    Directory of Open Access Journals (Sweden)

    Goldmann Torsten

    2010-04-01

    Full Text Available Abstract Background A large number of studies have investigated the effects of high tidal volume ventilation in mouse models. In contrast data on very short term effects of low tidal volume ventilation are sparse. Therefore we investigated the functional and structural effects of low tidal volume ventilation in mice. Methods 38 Male C57/Bl6 mice were ventilated with different tidal volumes (Vt 5, 7, and 10 ml/kg without or with application of PEEP (2 cm H2O. Four spontaneously breathing animals served as controls. Oxygen saturation and pulse rate were monitored. Lung function was measured every 5 min for at least 30 min. Afterwards lungs were removed and histological sections were stained for measurement of infiltration with polymorphonuclear leukocytes (PMN. Moreover, mRNA expression of macrophage inflammatory protein (MIP-2 and tumor necrosis factor (TNFα in the lungs was quantified using real time PCR. Results Oxygen saturation did not change significantly over time of ventilation in all groups (P > 0.05. Pulse rate dropped in all groups without PEEP during mechanical ventilation. In contrast, in the groups with PEEP pulse rate increased over time. These effects were not statistically significant (P > 0.05. Tissue damping (G and tissue elastance (H were significantly increased in all groups after 30 min of ventilation (P 0.05. Mechanical ventilation significantly increased infiltration of the lungs with PMN (P Conclusions Our data show that very short term mechanical ventilation with lower tidal volumes than 10 ml/kg did not reduce inflammation additionally. Formation of atelectasis and inadequate oxygenation with very low tidal volumes may be important factors. Application of PEEP attenuated inflammation.

  13. Targeted anti-inflammatory therapeutics in asthma and chronic obstructive lung disease

    OpenAIRE

    Durham, Andrew L.; Caramori, Gaetano; Chung, Kian F; Adcock, Ian M.

    2016-01-01

    Asthma and chronic obstructive pulmonary disease (COPD) are chronic inflammatory diseases of the airway, although the drivers and site of the inflammation differ between diseases. Asthmatics with a neutrophilic airway inflammation are associated with a poor response to corticosteroids, whereas asthmatics with eosinophilic inflammation respond better to corticosteroids. Biologicals targeting the Th2-eosinophil nexus such as anti–interleukin (IL)-4, anti–IL-5, and anti–IL-13 are ineffective in ...

  14. Up-Regulation of Claudin-6 in the Distal Lung Impacts Secondhand Smoke-Induced Inflammation

    Directory of Open Access Journals (Sweden)

    Joshua B. Lewis

    2016-10-01

    Full Text Available It has long been understood that increased epithelial permeability contributes to inflammation observed in many respiratory diseases. Recently, evidence has revealed that environmental exposure to noxious material such as cigarette smoke reduces tight junction barrier integrity, thus enhancing inflammatory conditions. Claudin-6 (Cldn6 is a tetraspanin transmembrane protein found within the tight junctional complex and is implicated in maintaining lung epithelial barriers. To test the hypothesis that increased Cldn6 ameliorates inflammation at the respiratory barrier, we utilized the Tet-On inducible transgenic system to conditionally over-express Clnd6 in the distal lung. Cldn6 transgenic (TG and control mice were continuously provided doxycycline from postnatal day (PN 30 until euthanasia date at PN90. A subset of Cldn6 TG and control mice were also subjected to daily secondhand tobacco smoke (SHS via a nose only inhalation system from PN30-90 and compared to room air (RA controls. Animals were euthanized on PN90 and lungs were harvested for histological and molecular characterization. Bronchoalveolar lavage fluid (BALF was procured for the assessment of inflammatory cells and molecules. Quantitative RT-PCR and immunoblotting revealed increased Cldn6 expression in TG vs. control animals and SHS decreased Cldn6 expression regardless of genetic up-regulation. Histological evaluations revealed no adverse pulmonary remodeling via Hematoxylin and Eosin (H&E staining or any qualitative alterations in the abundance of type II pneumocytes or proximal non-ciliated epithelial cells via staining for cell specific propeptide of Surfactant Protein-C (proSP-C or Club Cell Secretory Protein (CCSP, respectively. Immunoblotting and qRT-PCR confirmed the differential expression of Cldn6 and the pro-inflammatory cytokines TNF-α and IL-1β. As a general theme, inflammation induced by SHS exposure was influenced by the availability of Cldn6. These data reveal

  15. Up-Regulation of Claudin-6 in the Distal Lung Impacts Secondhand Smoke-Induced Inflammation

    Science.gov (United States)

    Lewis, Joshua B.; Milner, Dallin C.; Lewis, Adam L.; Dunaway, Todd M.; Egbert, Kaleb M.; Albright, Scott C.; Merrell, Brigham J.; Monson, Troy D.; Broberg, Dallin S.; Gassman, Jason R.; Thomas, Daniel B.; Arroyo, Juan A.; Reynolds, Paul R.

    2016-01-01

    It has long been understood that increased epithelial permeability contributes to inflammation observed in many respiratory diseases. Recently, evidence has revealed that environmental exposure to noxious material such as cigarette smoke reduces tight junction barrier integrity, thus enhancing inflammatory conditions. Claudin-6 (Cldn6) is a tetraspanin transmembrane protein found within the tight junctional complex and is implicated in maintaining lung epithelial barriers. To test the hypothesis that increased Cldn6 ameliorates inflammation at the respiratory barrier, we utilized the Tet-On inducible transgenic system to conditionally over-express Clnd6 in the distal lung. Cldn6 transgenic (TG) and control mice were continuously provided doxycycline from postnatal day (PN) 30 until euthanasia date at PN90. A subset of Cldn6 TG and control mice were also subjected to daily secondhand tobacco smoke (SHS) via a nose only inhalation system from PN30-90 and compared to room air (RA) controls. Animals were euthanized on PN90 and lungs were harvested for histological and molecular characterization. Bronchoalveolar lavage fluid (BALF) was procured for the assessment of inflammatory cells and molecules. Quantitative RT-PCR and immunoblotting revealed increased Cldn6 expression in TG vs. control animals and SHS decreased Cldn6 expression regardless of genetic up-regulation. Histological evaluations revealed no adverse pulmonary remodeling via Hematoxylin and Eosin (H&E) staining or any qualitative alterations in the abundance of type II pneumocytes or proximal non-ciliated epithelial cells via staining for cell specific propeptide of Surfactant Protein-C (proSP-C) or Club Cell Secretory Protein (CCSP), respectively. Immunoblotting and qRT-PCR confirmed the differential expression of Cldn6 and the pro-inflammatory cytokines TNF-α and IL-1β. As a general theme, inflammation induced by SHS exposure was influenced by the availability of Cldn6. These data reveal captivating

  16. Inflammation mediators in employees in chronic exposure to neurotoxicants

    Directory of Open Access Journals (Sweden)

    Galina Bodienkova

    2014-08-01

    Full Text Available Objectives: The aim of this work is to perform comparative estimation of cytokines levels in chlorinated hydrocarbons and metallic mercury exposure in employees in the dynamics of neurologic disorders formation. Material and Methods: The contents of cytokines IL-1β, IL-2, IL-4, IL-6, TNF-α, INF-γ were determined in blood sera using the method of hardphasic immunoferment analysis. The significance of different average values was assessed using the parametric and non-parametric criteria - Student (in normal distribution and Mann-Whitney tests taking into account the Bonferonni correction (non-difference from normal distribution. Results: It was shown that, a number of inflammation mediators with the dominance, depending on the expositional toxicant and expression of neurological deficiency, take part in the neurointoxication development. Healthy employees show pro-inflammatory responses with different expression degree, which dominate in the immune regulation processes regardless of the expositional factors (metallic mercury vapors and chlorinated hydrocarbons. Conclusions: The production intensity and interconnection between the pro- and anti-inflammatory cytokines may change in the occupational injuries of the nervous system development process. The decrease in the serum concentrations of cytokines along with the increase of clinical manifestation severity may prove dysregulation of the immune system, which promotes maintaining of pathological process and progradient process of neurointoxication. The most obvious is the imbalance of cytokines in the employees exposed to metallic mercury (in all the examined groups that increases neurointoxication in the distant period.

  17. Systemic interleukin-2 administration improves lung function and modulates chorioamnionitis-induced pulmonary inflammation in the ovine fetus.

    Science.gov (United States)

    Willems, Monique G M; Ophelders, Daan R M G; Nikiforou, Maria; Jellema, Reint K; Butz, Anke; Delhaas, Tammo; Kramer, Boris W; Wolfs, Tim G A M

    2016-01-01

    Chorioamnionitis, an inflammatory reaction of the fetal membranes to microbes, is an important cause of preterm birth and associated with inflammation-driven lung injury. However, inflammation in utero overcomes immaturity of the premature lung by inducing surfactant lipids and lung gas volume. Previously, we found that lipopolysaccharide (LPS)-induced chorioamnionitis resulted in pulmonary inflammation with increased effector T cells and decreased regulatory T cell (Treg) numbers. Because Tregs are crucial for immune regulation, we assessed the effects of interleukin (IL)-2-driven selective Treg expansion on the fetal lung in an ovine chorioamnionitis model. Instrumented fetuses received systemic prophylactic IL-2 treatment [118 days gestational age (dGA)] with or without subsequent exposure to intra-amniotic LPS (122 dGA). Following delivery at 129 dGA (term 147 dGA), pulmonary and systemic inflammation, morphological changes, lung gas volume, and phospholipid concentration were assessed. IL-2 pretreatment increased the FoxP3(+)/CD3(+) ratio, which was associated with reduced CD3-positive cells in the fetal lungs of LPS-exposed animals. Prophylactic IL-2 treatment did not prevent pulmonary accumulation of myeloperoxidase- and PU.1-positive cells or elevation of bronchoalveolar lavage fluid IL-8 and systemic IL-6 concentrations in LPS-exposed animals. Unexpectedly, IL-2 treatment improved fetal lung function of control lambs as indicated by increased disaturated phospholipids and improved lung gas volume. In conclusion, systemic IL-2 treatment in utero preferentially expanded Tregs and improved lung gas volume and disaturated phospholipids. These beneficial effects on lung function were maintained despite the moderate immunomodulatory effects of prophylactic IL-2 in the course of chorioamnionitis. PMID:26519206

  18. Alcohol Exposure Alters Mouse Lung Inflammation in Response to Inhaled Dust

    Directory of Open Access Journals (Sweden)

    Jill A. Poole

    2012-07-01

    Full Text Available Alcohol exposure is associated with increased lung infections and decreased mucociliary clearance. Occupational workers exposed to dusts from concentrated animal feeding operations (CAFOs are at risk for developing chronic inflammatory lung diseases. Agricultural worker co-exposure to alcohol and organic dust has been established, although little research has been conducted on the combination effects of alcohol and organic dusts on the lung. Previously, we have shown in a mouse model that exposure to hog dust extract (HDE collected from a CAFO results in the activation of protein kinase C (PKC, elevated lavage fluid cytokines/chemokines including interleukin-6 (IL-6, and the development of significant lung pathology. Because alcohol blocks airway epithelial cell release of IL-6 in vitro, we hypothesized that alcohol exposure would alter mouse lung inflammatory responses to HDE. To test this hypothesis, C57BL/6 mice were fed 20% alcohol or water ad libitum for 6 weeks and treated with 12.5% HDE by intranasal inhalation method daily during the final three weeks. Bronchoalveolar lavage fluid (BALF, tracheas and lungs were collected. HDE stimulated a 2–4 fold increase in lung and tracheal PKCε (epsilon activity in mice, but no such increase in PKCε activity was observed in dust-exposed mice fed alcohol. Similarly, alcohol-fed mice demonstrated significantly less IL-6 in lung lavage in response to dust than that observed in control mice instilled with HDE. TNFα levels were also inhibited in the alcohol and HDE-exposed mouse lung tissue as compared to the HDE only exposed group. HDE-induced lung inflammatory aggregates clearly present in the tissue from HDE only exposed animals were not visually detectable in the HDE/alcohol co-exposure group. Statistically significant weight reductions and 20% mortality were also observed in the mice co-exposed to HDE and alcohol. These data suggest that alcohol exposure depresses the ability

  19. Pro-calcitonin and inflammation in chronic hemodialysis

    Directory of Open Access Journals (Sweden)

    Hernán Trimarchi

    2013-10-01

    Full Text Available Procalcitonin (PCT has emerged as a marker of infection, a frequent complication in hemodialysis (HD. We analyzed PCT levels in chronic non-acutely infected HD subjects, assessed its correlation with inflammatory and nutritional markers and propose a PCT reference value for non-infected HD patients.In an observational cross-sectional study, 48 chronic HD patients and 36 controls were analyzed. Variables: age, gender, time on HD; diabetes; vascular access, PCT, C-reactive protein (CRP, albumin, malnutrition inflammatory score (MIS, hematocrit, leukocyte count, and body mass index (BMI. Subsequently, control (G1, n = 36, 43% vs. non-infected patients (G2, n = 48, 57% groups were compared. In control subjects (G1, age: 54.3 ± 13.7 years, range (r: 30-81; males: 19 (53%; median PCT 0.034 ng/ml (r: 0.02-0.08; median CRP 0.80 mg/dl (r: 0.36-3.9; p95 PCT level: 0.063 ng/ml. In G2, age: 60.2 ± 15.2 years; males 32 (67%, time on HD: 27.0 ± 24.4; diabetics: 19 (32%; median PCT: 0.26 ng/ml (r: 0.09-0.82; CRP: 1.1 mg/dl (r: 0.5-6.2; p95 PCT level: 0.8 ng/ml. In control subjects, PCT and CRP were significantly lower than in G2: PCT: 0.034 vs. 0.26 ng/ml, p = 0.0001; CRP: 0.8 vs. 1.1 mg/dl, p = 0.0004. PCT-CRP correlation in G2: ρ = 0.287, p = 0.048. PCT and CRP concentrations are elevated in chronic non-acutely infected HD subjects, independently of infection, diabetes and vascular access. A p95 PCT level of 0.8 ng/ml may be considered as the upper normal reference value in non-acutely infected HD subjects. The PCT cut-off level in HD is yet to be determined in HD.

  20. Adoptive transfer of IL-4Rα+ macrophages is sufficient to enhance eosinophilic inflammation in a mouse model of allergic lung inflammation

    Directory of Open Access Journals (Sweden)

    Ford Andrew Q

    2012-01-01

    Full Text Available Abstract Background The IL-4 receptor α (IL-4Rα chain has a broad expression pattern and participates in IL-4 and IL-13 signaling, allowing it to influence several pathological components of allergic lung inflammation. We previously reported that IL-4Rα expression on both bone marrow-derived and non-bone marrow-derived cells contributed to the severity of allergic lung inflammation. There was a correlation between the number of macrophages expressing the IL-4Rα, CD11b, and IAd, and the degree of eosinophilia in ovalbumin challenged mice. The engagement of the IL-4Rα by IL-4 or IL-13 is able to stimulate the alternative activation of macrophages (AAM. The presence of AAM has been correlated with inflammatory responses to parasites and allergens. Therefore, we hypothesized that IL-4Rα+ AAM play an active role in allergic lung inflammation. To directly determine the role of AAM in allergic lung inflammation, M-CSF-dependent macrophages (BMM were prepared from the bone-marrow of IL-4Rα positive and negative mice and transferred to IL-4RαxRAG2-/- mice. Wild type TH2 cells were provided exogenously. Results Mice receiving IL-4Rα+/+ BMM showed a marked increase in the recruitment of eosinophils to the lung after challenge with ovalbumin as compared to mice receiving IL-4Rα-/- BMM. As expected, the eosinophilic inflammation was dependent on the presence of TH2 cells. Furthermore, we observed an increase in cells expressing F4/80 and Mac3, and the AAM marker YM1/2 in the lungs of mice receiving IL-4Rα+/+ BMM. The BAL fluid from these mice contained elevated levels of eotaxin-1, RANTES, and CCL2. Conclusions These results demonstrate that transfer of IL-4Rα + macrophages is sufficient to enhance TH2-driven, allergic inflammation. They further show that stimulation of macrophages through IL-4Rα leads to their alternative activation and positive contribution to the TH2-driven allergic inflammatory response in the lung. Since an increase in AAM

  1. Prediction of chronic lung disease from the chest radiograph appearance at seven days of age

    International Nuclear Information System (INIS)

    The aim of this study was to assess if the chest radiograph appearance at seven days of age could be used to predict chronic lung disease. 60 preterm infants who were ventilated and/or had supplementary oxygen at seven days of age and had a chest radiograph performed at that postnatal age, were prospectively recruited. These chest radiographs were scored according to lung volume, presence of opacification, haziness, interstitial changes and cystic elements. 28 infants subsequently developed chronic lung disease; their median chest radiograph score was 5.5 which was significantly higher than that of the non-chronic lung disease infants. A chest radiograph score of 4 had a 71% sensitivity and 88% specificity in predicting chronic lung disease. It is concluded that chest radiograph appearance at seven days of age is a sensitive and specific predictor of chronic lung disease and thus could be used to indicate the need for preventive therapy. 22 refs., 1 fig., 1 tab

  2. A self-propagating matrix metalloprotease-9 (MMP-9 dependent cycle of chronic neutrophilic inflammation.

    Directory of Open Access Journals (Sweden)

    Xin Xu

    Full Text Available BACKGROUND: Chronic neutrophilic inflammation is a poorly understood feature in a variety of diseases with notable worldwide morbidity and mortality. We have recently characterized N-acetyl Pro-Gly-Pro (Ac-PGP as an important neutrophil (PMN chemoattractant in chronic inflammation generated from the breakdown of collagen by the actions of MMP-9. MMP-9 is present in the granules of PMNs and is differentially released during inflammation but whether Ac-PGP contributes to this ongoing proteolytic activity in chronic neutrophilic inflammation is currently unknown. METHODOLOGY/PRINCIPAL FINDINGS: Utilizing isolated primary blood PMNs from human donors, we found that Ac-PGP induces significant release of MMP-9 and concurrently activates the ERK1/2 MAPK pathway. This MMP-9 release is attenuated by an inhibitor of ERK1/2 MAPK and upstream blockade of CXCR1 and CXCR2 receptors with repertaxin leads to decreased MMP-9 release and ERK 1/2 MAPK activation. Supernatants obtained from PMNs stimulated by Ac-PGP generate more Ac-PGP when incubated with intact collagen ex vivo; this effect is inhibited by an ERK1/2 pathway inhibitor. Finally, clinical samples from individuals with CF demonstrate a notable correlation between Ac-PGP (as measured by liquid chromatography-tandem mass spectrometry and MMP-9 levels even when accounting for total PMN burden. CONCLUSIONS/SIGNIFICANCE: These data indicate that ECM-derived Ac-PGP could result in a feed-forward cycle by releasing MMP-9 from activated PMNs through the ligation of CXCR1 and CXCR2 and subsequent activation of the ERK1/2 MAPK, highlighting for the first time a matrix-derived chemokine (matrikine augmenting its generation through a discrete receptor/intracellular signaling pathway. These findings have notable implications to the development unrelenting chronic PMN inflammation in human disease.

  3. On the Role of Mechanics in Chronic Lung Disease

    Directory of Open Access Journals (Sweden)

    Mona Eskandari

    2013-12-01

    Full Text Available Progressive airflow obstruction is a classical hallmark of chronic lung disease, affecting more than one fourth of the adult population. As the disease progresses, the inner layer of the airway wall grows, folds inwards, and narrows the lumen. The critical failure conditions for airway folding have been studied intensely for idealized circular cross-sections. However, the role of airway branching during this process is unknown. Here, we show that the geometry of the bronchial tree plays a crucial role in chronic airway obstruction and that critical failure conditions vary significantly along a branching airway segment. We perform systematic parametric studies for varying airway cross-sections using a computational model for mucosal thickening based on the theory of finite growth. Our simulations indicate that smaller airways are at a higher risk of narrowing than larger airways and that regions away from a branch narrow more drastically than regions close to a branch. These results agree with clinical observations and could help explain the underlying mechanisms of progressive airway obstruction. Understanding growth-induced instabilities in constrained geometries has immediate biomedical applications beyond asthma and chronic bronchitis in the diagnostics and treatment of chronic gastritis, obstructive sleep apnea and breast cancer.

  4. Leukotriene B4 mediates macrophage influx and pulmonary hypertension in bleomycin-induced chronic neonatal lung injury.

    Science.gov (United States)

    Ee, Mong Tieng; Kantores, Crystal; Ivanovska, Julijana; Wong, Mathew J; Jain, Amish; Jankov, Robert P

    2016-08-01

    Systemically-administered bleomycin causes inflammation, arrested lung growth, and pulmonary hypertension (PHT) in the neonatal rat, similar to human infants with severe bronchopulmonary dysplasia (BPD). Leukotrienes (LTs) are inflammatory lipid mediators produced by multiple cell types in the lung. The major LTs, LTB4 and cysteinyl LTs, are suggested to contribute to BPD, but their specific roles remain largely unexplored in experimental models. We hypothesized that LTs are increased in bleomycin-induced BPD-like injury, and that inhibition of LT production would prevent inflammatory cell influx and thereby ameliorate lung injury. Rat pups were exposed to bleomycin (1 mg·kg(-1)·day(-1) ip) or vehicle (control) from postnatal days 1-14 and were treated with either zileuton (5-lipoxygenase inhibitor), montelukast (cysteinyl LT1 receptor antagonist), or SC57461A (LTA4 hydrolase inhibitor) 10 mg·kg(-1)·day(-1) ip. Bleomycin led to increased lung content of LTB4, but not cysteinyl LTs. Bleomycin-induced increases in tissue neutrophils and macrophages and lung contents of LTB4 and tumor necrosis factor-α were all prevented by treatment with zileuton. Treatment with zileuton or SC57461A also prevented the hemodynamic and structural markers of chronic PHT, including raised pulmonary vascular resistance, increased Fulton index, and arterial wall remodeling. However, neither treatment prevented impaired alveolarization or vascular hypoplasia secondary to bleomycin. Treatment with montelukast had no effect on macrophage influx, PHT, or on abnormal lung structure. We conclude that LTB4 plays a crucial role in lung inflammation and PHT in experimental BPD. Agents targeting LTB4 or LTB4-mediated signaling may have utility in infants at risk of developing BPD-associated PHT. PMID:27317685

  5. C-reactive protein, lung hyperinflation and heart rate variability in chronic obstructive pulmonary disease --a pilot study.

    Science.gov (United States)

    Corbo, Giuseppe Maria; Inchingolo, Riccardo; Sgueglia, Gregory Angelo; Lanza, Gaetano; Valente, Salvatore

    2013-04-01

    Chronic obstructive pulmonary disease (COPD) is associated to cardiovascular morbidity and mortality, and abnormalities of the autonomic nervous system have been described in subjects with severe disease. We studied heart rate variability (HRV) in COPD patients at rest and during the 6-minute Walk Test (6mWT) and the association with lung function impairment taking into account systemic inflammation. Thirty outpatients with stable COPD underwent lung function measurements, blood gas analysis, ECG Holter and transcutaneous pulse oximetry during 6mWT and then they were classified by BODE index. Also C-reactive protein (CRP) was measured. At rest, we observed a significant reduction of HRV for increasing BODE index. During the 6mWT, HRV tended to decrease in BODE 1 subjects whereas an increase was observed in BODE 2 and BODE 3-4 subjects. Subjects with elevated CRP values had a significant reduction in Standard Deviation of all normal RR intervals at rest (SDNN: p = 0.013), Total Power (TFA: p = 0.04) and Very Low Frequency band (VLF: p = 0.041). At rest, subjects with Inspiratory Capacity-to-Total Lung Capacity ratio (IC/TLC) hyperinflation indices. At rest and during submaximal exercise, COPD patients with moderate and severe disease had an abnormal cardiac autonomic modulation which was related to both systemic inflammation and lung function impairment.

  6. S-adenosylmethionine reduces airway inflammation and fibrosis in a murine model of chronic severe asthma via suppression of oxidative stress.

    Science.gov (United States)

    Yoon, Sun-Young; Hong, Gyong Hwa; Kwon, Hyouk-Soo; Park, Sunjoo; Park, So Young; Shin, Bomi; Kim, Tae-Bum; Moon, Hee-Bom; Cho, You Sook

    2016-06-03

    Increased oxidative stress has an important role in asthmatic airway inflammation and remodeling. A potent methyl donor, S-adenosylmethionine (SAMe), is known to protect against tissue injury and fibrosis through modulation of oxidative stress. The aim of this study was to evaluate the effect of SAMe on airway inflammation and remodeling in a murine model of chronic asthma. A mouse model was generated by repeated intranasal challenge with ovalbumin and Aspergillus fungal protease twice a week for 8 weeks. SAMe was orally administered every 24 h for 8 weeks. We performed bronchoalveolar lavage (BAL) fluid analysis and histopathological examination. The levels of various cytokines and 4-hydroxy-2-nonenal (HNE) were measured in the lung tissue. Cultured macrophages and fibroblasts were employed to evaluate the underlying anti-inflammatory and antifibrotic mechanisms of SAMe. The magnitude of airway inflammation and fibrosis, as well as the total BAL cell counts, were significantly suppressed in the SAMe-treated groups. A reduction in T helper type 2 pro-inflammatory cytokines and HNE levels was observed in mouse lung tissue after SAMe administration. Macrophages cultured with SAMe also showed reduced cellular oxidative stress and pro-inflammatory cytokine production. Moreover, SAMe treatment attenuated transforming growth factor-β (TGF-β)-induced fibronectin expression in cultured fibroblasts. SAMe had a suppressive effect on airway inflammation and fibrosis in a mouse model of chronic asthma, at least partially through the attenuation of oxidative stress and TGF-β-induced fibronectin expression. The results of this study suggest a potential role for SAMe as a novel therapeutic agent in chronic asthma.

  7. RGD-tagged helical rosette nanotubes aggravate acute lipopolysaccharide-induced lung inflammation

    Directory of Open Access Journals (Sweden)

    Suri SS

    2011-12-01

    Full Text Available Sarabjeet Singh Suri1, Steven Mills1, Gurpreet Kaur Aulakh1, Felaniaina Rakotondradany2, Hicham Fenniri2, Baljit Singh11Department of Veterinary Biomedical Sciences, University of Saskatchewan, Saskatoon; 2National Institute for Nanotechnology and Department of Chemistry, Edmonton, CanadaAbstract: Rosette nanotubes (RNT are a novel class of self-assembled biocompatible nanotubes that offer a built-in strategy for engineering structure and function through covalent tagging of synthetic self-assembling modules (G∧C motif. In this report, the G∧C motif was tagged with peptide Arg-Gly-Asp-Ser-Lys (RGDSK-G∧C and amino acid Lys (K-G∧C which, upon co-assembly, generate RNTs featuring RGDSK and K on their surface in predefined molar ratios. These hybrid RNTs, referred to as Kx/RGDSKy-RNT, where x and y refer to the molar ratios of K-G∧C and RGDSK–G∧C, were designed to target neutrophil integrins. A mouse model was used to investigate the effects of intravenous Kx/RGDSKy-RNT on acute lipopolysaccharide (LPS-induced lung inflammation. Healthy male C57BL/6 mice were treated intranasally with Escherichia coli LPS 80 µg and/or intravenously with K90/RGDSK10-RNT. Here we provide the first evidence that intravenous administration of K90/RGDSK10-RNT aggravates the proinflammatory effect of LPS in the mouse. LPS and K90/RGDSK10-RNT treatment groups showed significantly increased infiltration of polymorphonuclear cells in bronchoalveolar lavage fluid at all time points compared with the saline control. The combined effect of LPS and K90/RGDSK10-RNT was more pronounced than LPS alone, as shown by a significant increase in the expression of interleukin-1ß, MCP-1, MIP-1, and KC-1 in the bronchoalveolar lavage fluid and myeloperoxidase activity in the lung tissues. We conclude that K90/RGDSK10-RNT promotes acute lung inflammation, and when used along with LPS, leads to exaggerated immune response in the lung.Keywords: RGD peptide, helical rosette

  8. Pulmonary aspergillosis and aflatoxins in chronic lung diseases.

    Science.gov (United States)

    Ali, Sana; Malik, Abida; Shahid, Mohd; Bhargava, Rakesh

    2013-10-01

    Fungal infections of lung have become increasingly common during the last few decades. Aspergillosis and the role of aflatoxins in various chronic lung diseases have not been extensively studied. Bronchoalveolar lavage (BAL) samples and sera from 40 patients of chronic lung diseases were analyzed for galactomannan antigen (GM) and aflatoxin by enzyme-linked immunosorbent assay. Direct microscopy and culture of BAL samples were also done to detect the Aspergillus species. Results revealed that 15 (37.5 %) of the 40 patients had growth of Aspergillus on BAL culture. Out of these culture-positive cases, 13 (86.7 %) patients were positive for galactomannan antigen also. About 62.5 % cases did not show growth of Aspergillus in BAL culture. However, galactomannan antigen could be detected in 20 % of these patients. Overall, 20 % patients were diagnosed as proven invasive fungal disease (IFD), 32.5 % were of probable IFD, 17.5 % of possible IFD. Aspergillus growth was observed in 100 % of proven and 53.8 % of probable IFD cases. Galactomannan antigen was found in 100 % cases of proven and 76.9 % of probable IFD. Ten (25 %) patients were found to be positive for aflatoxins. It was detected in 6 (40 %) of culture-positive cases. About 62.5 % of the cases with proven IFD and 46.1 % of probable IFD had aflatoxin in their samples. Aflatoxin positivity was found to be more in patients with proven IFD than in probable IFD, and higher level of aflatoxins was detected in cases with proven IFD. Significant difference was observed in aflatoxin positivity among food grain workers when compared to other occupations.

  9. Increased arterial inflammation in individuals with stage 3 chronic kidney disease

    Energy Technology Data Exchange (ETDEWEB)

    Takx, Richard A.P. [Massachusetts General Hospital and Harvard Medical School, Cardiac MR PET CT Program, Boston, MA (United States); University Medical Center Utrecht, Department of Radiology, Utrecht (Netherlands); MacNabb, Megan H.; Emami, Hamed; Abdelbaky, Amr; Lavender, Zachary R. [Massachusetts General Hospital and Harvard Medical School, Cardiac MR PET CT Program, Boston, MA (United States); Singh, Parmanand [Massachusetts General Hospital and Harvard Medical School, Cardiac MR PET CT Program, Boston, MA (United States); New York Presbyterian Hospital, Weill Cornell Medical College, Division of Cardiology, New York, NY (United States); Di Carli, Marcelo; Taqueti, Viviany; Foster, Courtney [Brigham and Women' s Hospital and Harvard Medical School, Division of Radiology, Department of Medicine, Boston, MA (United States); Mann, Jessica; Comley, Robert A.; Weber, Chek Ing Kiu [F. Hoffmann-La Roche Ltd., Basel (Switzerland); Tawakol, Ahmed [Massachusetts General Hospital and Harvard Medical School, Cardiac MR PET CT Program, Boston, MA (United States); Massachusetts General Hospital and Harvard Medical School, Cardiology Division, Boston, MA (United States); Massachusetts General Hospital, Boston, MA (United States)

    2016-02-15

    While it is well known that patients with chronic kidney disease (CKD) are at increased risk for the development and progression of atherosclerosis, it is not known whether arterial inflammation is increased in mild CKD. The aim of this study was to compare arterial inflammation using {sup 18}F-FDG PET/CT in patients with CKD and in matched controls. This retrospective study included 128 patients undergoing FDG PET/CT imaging for clinical indications, comprising 64 patients with stage 3 CKD and 64 control patients matched by age, gender, and cancer history. CKD was defined according to guidelines using a calculated glomerular filtration rate (eGFR). Arterial inflammation was measured in the ascending aorta as FDG uptake on PET. Background FDG uptake (venous, subcutaneous fat and muscle) were recorded. Coronary artery calcification (CAC) was assessed using the CT images. The impact of CKD on arterial inflammation and CAC was then assessed. Arterial inflammation was higher in patients with CKD than in matched controls (standardized uptake value, SUV: 2.41 ± 0.49 vs. 2.16 ± 0.43; p = 0.002). Arterial SUV correlated inversely with eGFR (r = -0.299, p = 0.001). Venous SUV was also significantly elevated in patients with CKD, while subcutaneous fat and muscle tissue SUVs did not differ between groups. Moreover, arterial SUV remained significantly elevated in patients with CKD compared to controls after correcting for muscle and fat background, and also remained significant after adjusting for clinical risk factors. Further, CKD was associated with arterial inflammation (SUV) independent of the presence of subclinical atherosclerosis (CAC). Moderate CKD is associated with increased arterial inflammation beyond that of controls. Further, the increased arterial inflammation is independent of presence of subclinical atherosclerosis. Current risk stratification tools may underestimate the presence of atherosclerosis in patients with CKD and thereby the risk of

  10. Intra-Peritoneal Administration of Mitochondrial DNA Provokes Acute Lung Injury and Systemic Inflammation via Toll-Like Receptor 9.

    Science.gov (United States)

    Zhang, Lemeng; Deng, Songyun; Zhao, Shuangping; Ai, Yuhang; Zhang, Lina; Pan, Pinhua; Su, Xiaoli; Tan, Hongyi; Wu, Dongdong

    2016-01-01

    The pathogenesis of sepsis is complex. Mitochondrial dysfunction, which is responsible for energy metabolism, intrinsic apoptotic pathway, oxidative stress, and systemic inflammatory responses, is closely related with severe sepsis induced death. Mitochondria DNA (mtDNA) contain un-methylated cytosine phosphate guanine (CpG) motifs, which exhibit immune stimulatory capacities. The aim of this study was to investigate the role and mechanism of mtDNA release on lipopolysaccharide (LPS) induced acute lung injury (ALI) and systemic inflammation. Following LPS injection, plasma mtDNA copies peak at 8 h. Compared with wild-type (WT) mice, mtDNA in toll like receptor 4 knockout (TLR4 KO) mice were significantly decreased. MtDNA intra-peritoneal administration causes apparent ALI as demonstrated by increased lung injury score, bronchoalveolar lavage fluid (BALF) total protein and wet/dry (W/D) ratio; mtDNA injection also directly provokes systemic inflammation, as demonstrated by increased IL-1β, IL-6, high-mobility group protein B1 (HMGB1) level; while nuclear DNA (nDNA) could not induce apparent ALI and systemic inflammation. However, compared with WT mice, TLR4 KO could not protect from mtDNA induced ALI and systemic inflammation. Specific TLR9 inhibitor, ODN 2088 pretreatment can significantly attenuate mtDNA induced ALI and systemic inflammation, as demonstrated by improved lung injury score, decreased lung wet/dry ratio, BALF total protein concentration, and decreased systemic level of IL-1β, IL-6 and HMGB1. MtDNA administration activates the expression of p-P38 mitogen-activated protein kinases (MAPK) in lung tissue and specific TLR9 inhibitor pretreatment can attenuate this activation. Thus, LPS-induced mtDNA release occurs in a TLR4-dependent manner, and mtDNA causes acute lung injury and systemic inflammation in a TLR9-dependent and TLR4-independent manner. PMID:27589725

  11. Inhibitors of inflammation and endogenous surfactant pool size as modulators of lung injury with initiation of ventilation in preterm sheep

    Directory of Open Access Journals (Sweden)

    Polglase Graeme R

    2010-10-01

    Full Text Available Abstract Background Increased pro-inflammatory cytokines in tracheal aspirates correlate with the development of BPD in preterm infants. Ventilation of preterm lambs increases pro-inflammatory cytokines and causes lung inflammation. Objective We tested the hypothesis that selective inhibitors of pro-inflammatory signaling would decrease lung inflammation induced by ventilation in preterm newborn lambs. We also examined if the variability in injury response was explained by variations in the endogenous surfactant pool size. Methods Date-mated preterm lambs (n = 28 were operatively delivered and mechanically ventilated to cause lung injury (tidal volume escalation to 15 mL/kg by 15 min at age. The lambs then were ventilated with 8 mL/kg tidal volume for 1 h 45 min. Groups of animals randomly received specific inhibitors for IL-8, IL-1, or NF-κB. Unventilated lambs (n = 7 were the controls. Bronchoalveolar lavage fluid (BALF and lung samples were used to quantify inflammation. Saturated phosphatidylcholine (Sat PC was measured in BALF fluid and the data were stratified based on a level of 5 μmol/kg (~8 mg/kg surfactant. Results The inhibitors did not decrease the cytokine levels or inflammatory response. The inflammation increased as Sat PC pool size in BALF decreased. Ventilated lambs with a Sat PC level > 5 μmol/kg had significantly decreased markers of injury and lung inflammation compared with those lambs with Conclusion Lung injury caused by high tidal volumes at birth were decreased when endogenous surfactant pool sizes were larger. Attempts to decrease inflammation by blocking IL-8, IL-1 or NF-κB were unsuccessful.

  12. Age influence on mice lung tissue response to [i]Aspergillus fumigatus[/i] chronic exposure

    Directory of Open Access Journals (Sweden)

    Marta Kinga Lemieszek

    2015-02-01

    Full Text Available [b]Introduction and objective[/b]. Exposure to conidia of [i]Aspergillus fumigatus[/i] was described as a causative factor of a number of the respiratory system diseases, including asthma, chronic eosinophilic pneumonia, hypersensitivity pneumonitis and bronchopulmonary aspergillosis. The study investigates the effects of the repeated exposure to [i]A. fumigatus[/i] in mice pulmonary compartment. Our work tackles two, so far insufficiently addressed, important aspects of interaction between affected organism and[i] A. fumigatus[/i]: 1 recurrent character of exposure (characteristic for pathomechanism of the abovementioned disease states and 2 impact of aging, potentially important for the differentiation response to an antigen. [b]Materials and methods[/b]. In order to dissect alterations of the immune system involved with both aging and chronic exposure to [i]A. fumigatus[/i], we used 3- and 18-month-old C57BL/6J mice exposed to repeated[i] A. fumigatus[/i] inhalations for 7 and 28 days. Changes in lung tissue were monitored by histological and biochemical evaluation. Concentration of pro- and anti-inflammatory cytokines in lung homogenates was assessed by ELISA tests. [b]Results and conclusions. [/b]Our study demonstrated that chronic inflammation in pulmonary compartment, characterized by the significant increase of proinflammatory cytokines (IL1, IL6, IL10 levels, was the dominant feature of mice response to repeated [i]A. fumigatus[/i] inhalations. The pattern of cytokines’ profile in the course of exposure was similar in both age groups, however in old mice the growth of the cytokines’ levels was more pronounced (especially in case of IL1.

  13. The role of tumor necrosis factor in increased airspace epithelial permeability in acute lung inflammation.

    Science.gov (United States)

    Li, X Y; Donaldson, K; Brown, D; MacNee, W

    1995-08-01

    Increased airspace epithelial permeability is an early event in lung inflammation and injury. In this study, we have developed a rat model to study the mechanisms of the epithelial permeability to 125iodine-labeled bovine serum albumin (125I-BSA), instilled intratracheally during acute lung inflammation. Epithelial permeability was measured as the percentage of instilled 125I-BSA appearing in the blood. The increase in epithelial permeability induced by intratracheal instillation of heat-killed Corynebacterium parvum produced a peak influx of neutrophils into the bronchoalveolar space at 16 h, which occurred after the peak increase in epithelial permeability (8 h). The increased epithelial permeability induced by C. parvum did not appear to be protease- or oxidant-mediated. Depletion of peripheral blood neutrophils was achieved by an intravenous injection of anti-neutrophil polyclonal antibody. The consequent profound reduction in neutrophil and macrophage influx into the airspaces 8 h after instillation of C. parvum reduced the epithelial permeability to control values. Bronchoalveolar lavage (BAL) leukocytes from rats 8 h, but not 16 h, after treatment with C. parvum caused a modest increase in epithelial permeability when re-instilled intratracheally into control rat lungs. Separation of the leukocytes before re-instillation indicated that macrophages rather than neutrophils were predominantly responsible for the increased epithelial permeability. The presence of dramatically increased levels of tumor necrosis factor (TNF) in BAL 8 h in contrast to a slight increase in BAL 16 h after C. parvum, the release of TNF from 8 h macrophages, the increased epithelial permeability induced by TNF in epithelial monolayers in vitro, and the inhibition of C. parvum-induced epithelial permeability by TNF antibody support the premise that TNF is a major player in the increased epithelial permeability that occurs during C. parvum-induced acute alveolitis. PMID:7626286

  14. Effects of dexmedetomidine on oxygenation and lung mechanics in patients with moderate chronic obstructive pulmonary disease undergoing lung cancer surgery

    OpenAIRE

    Lee, Su Hyun; Kim, Namo; Lee, Chang Yeong; Ban, Min Gi; Oh, Young Jun

    2015-01-01

    BACKGROUND Chronic obstructive pulmonary disease (COPD) is a risk factor that increases the incidence of postoperative cardiopulmonary morbidity and mortality after lung resection. Dexmedetomidine, a selective α2-adrenoreceptor agonist, has been reported previously to attenuate intrapulmonary shunt during one-lung ventilation (OLV) and to alleviate bronchoconstriction. OBJECTIVE The objective is to determine whether dexmedetomidine improves oxygenation and lung mechanics in patients with mode...

  15. Implanted neural electrodes cause chronic, local inflammation that is correlated with local neurodegeneration

    Science.gov (United States)

    McConnell, George C.; Rees, Howard D.; Levey, Allan I.; Gutekunst, Claire-Anne; Gross, Robert E.; Bellamkonda, Ravi V.

    2009-10-01

    Prosthetic devices that are controlled by intracortical electrodes recording one's 'thoughts' are a reality today, and no longer merely in the realm of science fiction. However, widespread clinical use of implanted electrodes is hampered by a lack of reliability in chronic recordings, independent of the type of electrodes used. One major hypothesis has been that astroglial scar electrically impedes the electrodes. However, there is a temporal discrepancy between stabilization of scar's electrical properties and recording failure with recording failure lagging by 1 month. In this study, we test a possible explanation for this discrepancy: the hypothesis that chronic inflammation, due to the persistent presence of the electrode, causes a local neurodegenerative state in the immediate vicinity of the electrode. Through modulation of chronic inflammation via stab wound, electrode geometry and age-matched control, we found that after 16 weeks, animals with an increased level of chronic inflammation were associated with increased neuronal and dendritic, but not axonal, loss. We observed increased neuronal and dendritic loss 16 weeks after implantation compared to 8 weeks after implantation, suggesting that the local neurodegenerative state is progressive. After 16 weeks, we observed axonal pathology in the form of hyperphosphorylation of the protein tau in the immediate vicinity of the microelectrodes (as observed in Alzheimer's disease and other tauopathies). The results of this study suggest that a local, late onset neurodegenerative disease-like state surrounds the chronic electrodes and is a potential cause for chronic recording failure. These results also inform strategies to enhance our capability to attain reliable long-term recordings from implantable electrodes in the CNS.

  16. Hydrogen Sulfide Prevents and Partially Reverses Ozone-Induced Features of Lung Inflammation and Emphysema in Mice.

    Science.gov (United States)

    Li, Feng; Zhang, Pengyu; Zhang, Min; Liang, Li; Sun, Xiaoyuan; Li, Min; Tang, Yueqin; Bao, Aihua; Gong, Jicheng; Zhang, Junfeng; Adcock, Ian; Chung, Kian Fan; Zhou, Xin

    2016-07-01

    Hydrogen sulfide (H2S), a novel signaling gasotransmitter in the respiratory system, may have antiinflammatory properties in the lung. We examined the preventive and therapeutic effects of H2S on ozone-induced features of lung inflammation and emphysema. C57/BL6 mice were exposed to ozone or filtered air over 6 weeks. Sodium hydrogen sulfide (NaHS), an H2S donor, was administered to the mice either before ozone exposure (preventive effect) or after completion of 6 weeks of ozone exposure (therapeutic effect). The ozone-exposed mice developed emphysema, measured by micro-computed tomography and histology, airflow limitation, measured by the forced maneuver system, and increased lung inflammation with augmented IL-1β, IL-18, and matrix metalloproteinase-9 (MMP-9) gene expression. Ozone-induced changes were associated with increased Nod-like receptor pyrin domain containing 3 (NLRP3)-caspase-1 activation and p38 mitogen-activated protein kinase phosphorylation and decreased Akt phosphorylation. NaHS both prevented and reversed lung inflammation and emphysematous changes in alveolar space. In contrast, NaHS prevented, but did not reverse, ozone-induced airflow limitation and bronchial structural remodeling. In conclusion, NaHS administration prevented and partially reversed ozone-induced features of lung inflammation and emphysema via regulation of the NLRP3-caspase-1, p38 mitogen-activated protein kinase, and Akt pathways. PMID:26731380

  17. Living near a Major Road in Beijing: Association with Lower Lung Function, Airway Acidification, and Chronic Cough

    Science.gov (United States)

    Hu, Zhan-Wei; Zhao, Yan-Ni; Cheng, Yuan; Guo, Cui-Yan; Wang, Xi; Li, Nan; Liu, Jun-Qing; Kang, Hui; Xia, Guo-Guang; Hu, Ping; Zhang, Ping-Ji; Ma, Jing; Liu, Ying; Zhang, Cheng; Su, Li; Wang, Guang-Fa

    2016-01-01

    Background: The effects of near-road pollution on lung function in China have not been well studied. We aimed to investigate the effects of long-term exposure to traffic-related air pollution on lung function, airway inflammation, and respiratory symptoms. Methods: We enrolled 1003 residents aged 57.96 ± 8.99 years living in the Shichahai Community in Beijing. Distances between home addresses and the nearest major roads were measured to calculate home-road distance. We used the distance categories 1, 2, and 3, representing 200 m, respectively, as the dose indicator for traffic-related air pollution exposure. Lung function, exhaled breath condensate (EBC) pH, and interleukin 6 levels were measured. As a follow-up, 398 participants had a second lung function assessment about 3 years later, and lung function decline was also examined as an outcome. We used regression analysis to assess the impacts of home-road distance on lung function and respiratory symptoms. As the EBC biomarker data were not normally distributed, we performed correlation analysis between home-road distance categories and EBC biomarkers. Results: Participants living a shorter distance from major roads had lower percentage of predicted value of forced expiratory volume in 1 s (FEV1% −1.54, 95% confidence interval [CI]: −0.20 to −2.89). The odds ratio for chronic cough was 2.54 (95% CI: 1.57–4.10) for category 1 and 1.97 (95% CI: 1.16–3.37) for category 2, compared with category 3. EBC pH was positively correlated with road distance (rank correlation coefficient of Spearman [rs] = 0.176, P air pollution in people who live near major roads in Beijing is associated with lower lung function, airway acidification, and a higher prevalence of chronic cough. EBC pH is a potential useful biomarker for evaluating air pollution exposure. PMID:27625090

  18. Lung Function, Airway Inflammation, and Polycyclic Aromatic Hydrocarbons Exposure in Mexican Schoolchildren

    Science.gov (United States)

    Barraza-Villarreal, Albino; Escamilla-Nuñez, Maria Consuelo; Schilmann, Astrid; Hernandez-Cadena, Leticia; Li, Zheng; Romanoff, Lovisa; Sjödin, Andreas; Del Río-Navarro, Blanca Estela; Díaz-Sanchez, David; Díaz-Barriga, Fernando; Sly, Peter; Romieu, Isabelle

    2015-01-01

    Objective To determine the association of exposure to polycyclic aromatic hydrocarbons (PAHs) with lung function and pH of exhaled breath condensate (EBC) in Mexican schoolchildren. Methods A pilot study was performed in a subsample of 64 schoolchildren from Mexico City. Lung function and pH of EBC were measured and metabolites of PAHs in urine samples were determined. The association was analyzed using robust regression models. Results A 10% increase in the concentrations of 2-hydroxyfluorene was significantly negatively associated with forced expiratory volume in 1 second (−11.2 mL, 95% CI: −22.2 to −0.02), forced vital capacity (−11.6 mL, 95% CI: −22.9 to −0.2), and pH of EBC (−0.035, 95% CI: −0.066 to −0.005). Conclusion Biomarkers of PAHs exposure were inversely associated with lung function and decrease of ph of EBC as a marker of airway inflammation in Mexican schoolchildren. PMID:24500378

  19. A New Mouse Model That Spontaneously Develops Chronic Liver Inflammation and Fibrosis.

    Directory of Open Access Journals (Sweden)

    Nina Fransén-Pettersson

    Full Text Available Here we characterize a new animal model that spontaneously develops chronic inflammation and fibrosis in multiple organs, the non-obese diabetic inflammation and fibrosis (N-IF mouse. In the liver, the N-IF mouse displays inflammation and fibrosis particularly evident around portal tracts and central veins and accompanied with evidence of abnormal intrahepatic bile ducts. The extensive cellular infiltration consists mainly of macrophages, granulocytes, particularly eosinophils, and mast cells. This inflammatory syndrome is mediated by a transgenic population of natural killer T cells (NKT induced in an immunodeficient NOD genetic background. The disease is transferrable to immunodeficient recipients, while polyclonal T cells from unaffected syngeneic donors can inhibit the disease phenotype. Because of the fibrotic component, early on-set, spontaneous nature and reproducibility, this novel mouse model provides a unique tool to gain further insight into the underlying mechanisms mediating transformation of chronic inflammation into fibrosis and to evaluate intervention protocols for treating conditions of fibrotic disorders.

  20. FOS EXPRESSION IN LUMBARSACRAL SPINAL CORD AND MEDULLA OBLONGATA INDUCED BY CHRONIC COLONIC INFLAMMATION IN RATS

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    Objective To investigate Fos expression in rat lumbarsacral spinal cord and medulla oblongata induced by chronic colonic inflammation. Methods Thirty-three male Sprague-Dawley rats were randomly divided into two groups: experimental group: colonic inflammation was induced in seventeen rats by intraluminal administration of trinitrobenzenesulfonic acid (TNBS); control group: saline was administered intraluminally in sixteen rats; After 3, 7, 14 and 28 days of administration, lumbarsacral spinal cord and medulla oblongata were removed and processed for Fos immunohistochemistry. Results Fos-immunoreactive (Fos-IR) neurons induced by TNBS administration were primarily distributed in deep laminae (laminae Ⅲ-Ⅳ,Ⅴ-Ⅵ) in the spinal dorsal horn and in medullary visceral zone (MVZ) in the medulla oblongata. The number of Fos-IR cells in the spinal cord and MVZ in rats after 7 and 14 days of TNBS administration were significantly higher than that in the control rats (P<0.05). After 28 days of TNBS instillation, the number of Fos-IR neurons in MVZ decreased and became comparable to the control group. However, the number of Fos cells in the spinal cord in some rats were still significantly increased compared with the control rats (P<0.05). Conclusion Fos-IR neurons after colonic inflammation recovery may play an important role in the development of visceral hypersensitivity. Medulla oblongata was a less important structure than the spinal cord in inducing visceral hypersensitivity after chronic colonic inflammation.

  1. Bubbly and cystic appearance in chronic lung disease: Is this diagnosed as Wilson-Mikity syndrome?

    Science.gov (United States)

    Namba, Fumihiko; Fujimura, Masanori; Tamura, Masanori

    2016-04-01

    Wilson-Mikity syndrome (WMS) was first reported in 1960 by Wilson and Mikity. They described preterm infants who developed areas of cystic emphysema in the first month of life with subsequent progression to chronic lung disease (CLD) of infancy, although these infants did not exhibit early respiratory distress, such as respiratory distress syndrome (RDS). This condition was widely accepted over the next 20 years, but WMS is now rarely mentioned and is commonly considered an anachronism. In Japan, CLD is classified into six types according to the presence of RDS and/or intrauterine inflammation and appearance on chest X-ray. One type of CLD (type III, which accounts for 13.5% of all CLD) is defined as history of intrauterine inflammation and the typical bubbly and cystic appearance on chest X-ray described in the original report of WMS. There is insufficient evidence to determine whether WMS exists or whether WMS is relatively common only in Japan and not in other countries. It is important, however, to distinguish this type of CLD from other types because the strategy for the prevention or treatment of CLD should be different according to its origin, cause, and risk factors.

  2. Elevated [11C]-D-Deprenyl Uptake in Chronic Whiplash Associated Disorder Suggests Persistent Musculoskeletal Inflammation

    OpenAIRE

    Linnman, Clas; Appel, Lieuwe; Fredrikson, Mats; Gordh, Torsten; Söderlund, Anne; Långström, Bengt; Engler, Henry

    2011-01-01

    There are few diagnostic tools for chronic musculoskeletal pain as structural imaging methods seldom reveal pathological alterations. This is especially true for Whiplash Associated Disorder, for which physical signs of persistent injuries to the neck have yet to be established. Here, we sought to visualize inflammatory processes in the neck region by means Positron Emission Tomography using the tracer 11C-D-deprenyl, a potential marker for inflammation. Twenty-two patients with enduring pain...

  3. Relationship between airway inflammation and remodeling in patients with asthma and chronic obstructive pulmonary disease

    OpenAIRE

    Górska K; Krenke R; Kosciuch J; Korczynski P; Zukowska M; Domagala-Kulawik J; Maskey-Warzechowska M; Chazan R

    2009-01-01

    Abstract Despite a number of important differences in the pathogenesis, course and prognosis of asthma and chronic obstructive pulmonary disease (COPD), these two entities also have common features with airway inflammation being one of them. Airway remodeling is a characteristic feature of asthma, but data on the bronchial wall thickening in COPD patients are still scarce. Aim To assess the relation between the inflammatory cell count in the bronchoalveolar lavage fluid (BALF) and thickness o...

  4. Inflammation Enhances the Risks of Stroke and Death in Chronic Chagas Disease Patients

    OpenAIRE

    Guedes, Paulo Marcos Matta; de Andrade, Cléber Mesquita; Nunes, Daniela Ferreira; de Sena Pereira, Nathalie; Queiroga, Tamyres Bernadete Dantas; Machado-Coelho, George Luiz Lins; Nascimento, Manuela Sales Lima; Do-Valle-Matta, Maria Adelaide; da Câmara, Antônia Cláudia Jácome; Chiari, Egler; Galvão, Lúcia Maria da Cunha

    2016-01-01

    Ischemic strokes have been implicated as a cause of death in Chagas disease patients. Inflammation has been recognized as a key component in all ischemic processes, including the intravascular events triggered by vessel interruption, brain damage and repair. In this study, we evaluated the association between inflammatory markers and the death risk (DR) and stroke risk (SR) of patients with different clinical forms of chronic Chagas disease. The mRNA expression levels of cytokines, transcript...

  5. Is Chronic Inflammation a Possible Cause of Obesity-Related Depression?

    OpenAIRE

    Magdalena Olszanecka-Glinianowicz; Barbara Zahorska-Markiewicz; Piotr Kocełak; Joanna Janowska; Elżbieta Semik-Grabarczyk; Tomasz Wikarek; Wojciech Gruszka; Piotr Dąbrowski

    2009-01-01

    Adult obesity has been associated with depression, especially in women. Whether depression leads to obesity or obesity causes depression is unclear. Chronic inflammation is observed in obesity and depression. In 63 obese women without additional diseases depression level was assessed with the Beck's questionnaire. After evaluation of depression level study group was divided into groups according to the mood status (A—without depression, B—mild depression, and C—severe depression), and serum c...

  6. Cigarette Smoke Activates the Proto-Oncogene c-Src to Promote Airway Inflammation and Lung Tissue Destruction

    OpenAIRE

    Geraghty, Patrick; Hardigan, Andrew; Foronjy, Robert F.

    2014-01-01

    The diagnosis of chronic obstructive pulmonary disease (COPD) confers a 2-fold increased lung cancer risk even after adjusting for cigarette smoking, suggesting that common pathways are operative in both diseases. Although the role of the tyrosine kinase c-Src is established in lung cancer, less is known about its impact in other lung diseases, such as COPD. This study examined whether c-Src activation by cigarette smoke contributes to the pathogenesis of COPD. Cigarette smoke increased c-Src...

  7. Lung hyperinflation in chronic obstructive pulmonary disease: mechanisms, clinical implications and treatment.

    Science.gov (United States)

    Langer, Daniel; Ciavaglia, Casey E; Neder, J Alberto; Webb, Katherine A; O'Donnell, Denis E

    2014-12-01

    Lung hyperinflation is highly prevalent in patients with chronic obstructive pulmonary disease and occurs across the continuum of the disease. A growing body of evidence suggests that lung hyperinflation contributes to dyspnea and activity limitation in chronic obstructive pulmonary disease and is an important independent risk factor for mortality. In this review, we will summarize the recent literature on pathogenesis and clinical implications of lung hyperinflation. We will outline the contribution of lung hyperinflation to exercise limitation and discuss its impact on symptoms and physical activity. Finally, we will examine the physiological rationale and efficacy of selected pharmacological and non-pharmacological 'lung deflating' interventions aimed at improving symptoms and physical functioning.

  8. LPS-Induced Lung Inflammation in Marmoset Monkeys – An Acute Model for Anti-Inflammatory Drug Testing

    OpenAIRE

    Sophie Seehase; Hans-Dieter Lauenstein; Christina Schlumbohm; Simone Switalla; Vanessa Neuhaus; Christine Förster; Hans-Gerd Fieguth; Olaf Pfennig; Eberhard Fuchs; Franz-Josef Kaup; Martina Bleyer; Hohlfeld, Jens M.; Armin Braun; Katherina Sewald; Sascha Knauf

    2012-01-01

    Increasing incidence and substantial morbidity and mortality of respiratory diseases requires the development of new human-specific anti-inflammatory and disease-modifying therapeutics. Therefore, new predictive animal models that closely reflect human lung pathology are needed. In the current study, a tiered acute lipopolysaccharide (LPS)-induced inflammation model was established in marmoset monkeys (Callithrix jacchus) to reflect crucial features of inflammatory lung diseases. Firstly, in ...

  9. Discovery of the drivers of inflammation induced chronic low back pain: from bacteria to diabetes.

    Science.gov (United States)

    Gorth, Deborah J; Shapiro, Irving M; Risbud, Makarand V

    2015-10-01

    The intervertebral disc is a unique avascular organ that supports axial skeleton flexion and rotation. The high proteoglycan content of the nucleus pulposus tissue, present at the center of the disc, is pivotal for its mechanical function, distribution of compressive loads. Chronic low back pain, a prevalent and costly condition, is strongly associated with disc degeneration. Degenerated discs exhibit high levels of inflammatory cytokines, matrix catabolizing enzymes, and an overall reduction in proteoglycan content. Although the cytokine profile of diseased discs has been widely studied, little is known of what initiates and drives inflammation and subsequent low back pain. Recent studies have shown that anaerobic bacteria are present in a high percentage of painful, herniated discs and long-term treatment with antibiotics resolves symptoms associated with chronic low back pain. It is thought that these anaerobic bacteria in the disc may stimulate inflammation through toll-like receptors to further exacerbate disc degeneration. Despite the promise and novelty of this theory, there are other possible inflammatory mediators that need careful consideration. The metabolic environment associated with diabetes and atypical matrix degradation products also have the ability to activate many of the same inflammatory pathways as seen during microbial infection. It is therefore imperative that the research community must investigate the contribution of all possible drivers of inflammation to address the wide spread problem of discogenic chronic low back pain. PMID:26562470

  10. Lung hyperinflation in chronic obstructive pulmonary disease: mechanisms, clinical implications and treatment

    OpenAIRE

    Langer, Daniel; Ciavaglia, Casey E; Neder, J. Alberto; Katherine A. Webb; O'Donnell, Denis E.

    2014-01-01

    Lung hyperinflation is highly prevalent in patients with chronic obstructive pulmonary disease and occurs across the continuum of the disease. A growing body of evidence suggests that lung hyperinflation contributes to dyspnea and activity limitation in chronic obstructive pulmonary disease and is an important independent risk factor for mortality. In this review, we will summarize the recent literature on pathogenesis and clinical implications of lung hyperinflation. We will outline the cont...

  11. Lung inflammation and genotoxicity following pulmonary exposure to nanoparticles in ApoE-/- mice

    Directory of Open Access Journals (Sweden)

    Ladefoged Ole

    2009-01-01

    Full Text Available Abstract Background The toxic and inflammatory potential of 5 different types of nanoparticles were studied in a sensitive model for pulmonary effects in apolipoprotein E knockout mice (ApoE-/-. We studied the effects instillation or inhalation Printex 90 of carbon black (CB and compared CB instillation in ApoE-/- and C57 mice. Three and 24 h after pulmonary exposure, inflammation was assessed by mRNA levels of cytokines in lung tissue, cell composition, genotoxicity, protein and lactate dehydrogenase activity in broncho-alveolar lavage (BAL fluid. Results Firstly, we found that intratracheal instillation of CB caused far more pulmonary toxicity in ApoE-/- mice than in C57 mice. Secondly, we showed that instillation of CB was more toxic than inhalation of a presumed similar dose with respect to inflammation in the lungs of ApoE-/- mice. Thirdly, we compared effects of instillation in ApoE-/- mice of three carbonaceous particles; CB, fullerenes C60 (C60 and single walled carbon nanotubes (SWCNT as well as gold particles and quantum dots (QDs. Characterization of the instillation media revealed that all particles were delivered as agglomerates and aggregates. Significant increases in Il-6, Mip-2 and Mcp-1 mRNA were detected in lung tissue, 3 h and 24 h following instillation of SWCNT, CB and QDs. DNA damage in BAL cells, the fraction of neutrophils in BAL cells and protein in BAL fluid increased statistically significantly. Gold and C60 particles caused much weaker inflammatory responses. Conclusion Our data suggest that ApoE-/- model is sensitive for evaluating particle induced inflammation. Overall QDs had greatest effects followed by CB and SWCNT with C60 and gold being least inflammatory and DNA-damaging. However the gold was used at a much lower mass dose than the other particles. The strong effects of QDs were likely due to Cd release. The surface area of the instilled dose correlated well the inflammatory response for low toxicity particles.

  12. P. aeruginosa in the paranasal sinuses and transplanted lungs have similar adaptive mutations as isolates from chronically infected CF lungs

    DEFF Research Database (Denmark)

    Ciofu, Oana; Johansen, Helle Krogh; Aanaes, Kasper;

    2013-01-01

    BACKGROUND: Pseudomonas aeruginosa cells are present as biofilms in the paranasal sinuses and the lungs of chronically infected cystic fibrosis (CF) patients. Since different inflammatory responses and selective antibiotic pressures are acting in the sinuses compared with the lungs, we compared...... the adaptive profiles of mucoid and non-mucoid isolates from the two locations. METHODS: We studied the genetic basis of phenotypic diversification and gene expression profiles in sequential lung and sinus P. aeruginosa isolates from four chronically infected CF patients, including pre- and post-lung...... transplantation isolates. RESULTS: The same phenotypes caused by similar mutations and similar gene expression profiles were found in mucoid and non-mucoid isolates from the paranasal sinuses and from the lungs before and after transplantation. CONCLUSION: Bilateral exchange of P. aeruginosa isolates between...

  13. Prevalence and risk factors for chronic bronchitis and farmer's lung in French dairy farmers.

    OpenAIRE

    Dalphin, J.C.; Debieuvre, D.; Pernet, D.; Maheu, M F; Polio, J. C.; Toson, B.; Dubiez, A.; Monnet, E; Laplante, J. J.; Depierre, A

    1993-01-01

    The prevalence of chronic bronchitis and of clinical farmer's lung was studied in 30 districts of the French Doubs province in relation to individual (age, sex, smoking) and geographical (altitude) factors. 5703 exclusively dairy farmers (response rate 83%) participated in the study by answering a medical questionnaire. Prevalences of chronic bronchitis and clinical farmer's lung were 9.3% and 1.4% respectively. A logistic regression model was used to evaluate risk factors for chronic bronchi...

  14. Cerebellar white matter inflammation and demyelination in chronic relapsing experimental allergic encephalomyelitis

    DEFF Research Database (Denmark)

    Wanscher, B.; Sørensen, P. S.; Juhler, M.;

    1993-01-01

    Experimental allergic encephalomyelitis, demyelination, inflammation, immunology, neuropathology......Experimental allergic encephalomyelitis, demyelination, inflammation, immunology, neuropathology...

  15. DO ACUTE PHASE PROTEINS REFLECT SEVERITY OF INFLAMMATION IN RAT MODELS OF POLLUTANT-INDUCED LUNG INJURY?

    Science.gov (United States)

    Title: DO ACUTE PHASE PROTEINS REFLECT THE SEVERITY OF INFLAMMATION IN RAT MODELS OF POLLUTANT-INDUCED LUNG INJURY?M. C. Schladweiler, BS 1, P. S. Gilmour, PhD 2, D. L. Andrews, BS 1, D. L. Costa, ScD 1, A. D. Ledbetter, BS 1, K. E. Pinkerton, PhD 3 and U. P. Kodavanti, ...

  16. Biomass Smoke Exposure Enhances Rhinovirus-Induced Inflammation in Primary Lung Fibroblasts.

    Science.gov (United States)

    Capistrano, Sarah J; Zakarya, Razia; Chen, Hui; Oliver, Brian G

    2016-01-01

    Biomass smoke is one of the major air pollutants and contributors of household air pollution worldwide. More than 3 billion people use biomass fuels for cooking and heating, while other sources of exposure are from the occurrence of bushfires and occupational conditions. Persistent biomass smoke exposure has been associated with acute lower respiratory infection (ALRI) as a major environmental risk factor. Children under the age of five years are the most susceptible in developing severe ALRI, which accounts for 940,000 deaths globally. Around 90% of cases are attributed to viral infections, such as influenza, adenovirus, and rhinovirus. Although several epidemiological studies have generated substantial evidence of the association of biomass smoke and respiratory infections, the underlying mechanism is still unknown. Using an in vitro model, primary human lung fibroblasts were stimulated with biomass smoke extract (BME), specifically investigating hardwood and softwood types, and human rhinovirus-16 for 24 h. Production of pro-inflammatory mediators, such as IL-6 and IL-8, were measured via ELISA. Firstly, we found that hardwood and softwood smoke extract (1%) up-regulate IL-6 and IL-8 release (p ≤ 0.05). In addition, human rhinovirus-16 further increased biomass smoke-induced IL-8 in fibroblasts, in comparison to the two stimulatory agents alone. We also investigated the effect of biomass smoke on viral susceptibility by measuring viral load, and found no significant changes between BME exposed and non-exposed infected fibroblasts. Activated signaling pathways for IL-6 and IL-8 production by BME stimulation were examined using signaling pathway inhibitors. p38 MAPK inhibitor SB239063 significantly attenuated IL-6 and IL-8 release the most (p ≤ 0.05). This study demonstrated that biomass smoke can modulate rhinovirus-induced inflammation during infection, which can alter the severity of the disease. The mechanism by which biomass smoke exposure increases

  17. Chronic Mild Prenatal Stress Exacerbates the Allergen-Induced Airway Inflammation in Rats

    Directory of Open Access Journals (Sweden)

    Paulo J. Nogueira

    1999-01-01

    Full Text Available The effects of chronic mild prenatal stress on leukocyte infiltration into the airways was investigated in rat offspring. The chronic prenatal stress consisted of transitory and variable changes in the rat's living conditions. Offspring at adult age were actively sensitized (day 0 and intratracheally challenged (day 14 with ovalbumin. Bronchoalveolar lavage was performed in the offspring at 48 h after intratracheal challenge with ovalbumin. A significant increase in total leukocyte infiltration was observed in the nonstressed offspring group and this was associated with a marked recruitment of eosinophils without a significant effect on the influx of neutrophils and mononuclear cells. In the prenatal stressed offspring, the counts of both total leukocyte and eosinophils, as well as mononuclear cells, was increased by 50% compared to the non-stressed offspring. We provide here the first experimental evidence that chronic mild unpredictable prenatal stress produces a marked increase in the allergen-induced airway inflammation in the rat offspring.

  18. Inflammatory mechanisms in the lung

    Directory of Open Access Journals (Sweden)

    B Moldoveanu

    2008-12-01

    Full Text Available B Moldoveanu1, P Otmishi1, P Jani1, J Walker1,2, X Sarmiento3, J Guardiola1, M Saad1, Jerry Yu11Department of Medicine, University of Louisville, Louisville, KY, USA, 40292; 2Department of Respiratory Therapy, Bellarmine University, Louisville, KY, USA, 40205; 3Intensive Care Medicine Service, University Hospital Germans Trias i Pujol, Badalona, Spain 08916Abstract: Inflammation is the body’s response to insults, which include infection, trauma, and hypersensitivity. The inflammatory response is complex and involves a variety of mechanisms to defend against pathogens and repair tissue. In the lung, inflammation is usually caused by pathogens or by exposure to toxins, pollutants, irritants, and allergens. During inflammation, numerous types of inflammatory cells are activated. Each releases cytokines and mediators to modify activities of other inflammatory cells. Orchestration of these cells and molecules leads to progression of inflammation. Clinically, acute inflammation is seen in pneumonia and acute respiratory distress syndrome (ARDS, whereas chronic inflammation is represented by asthma and chronic obstructive pulmonary disease (COPD. Because the lung is a vital organ for gas exchange, excessive inflammation can be life threatening. Because the lung is constantly exposed to harmful pathogens, an immediate and intense defense action (mainly inflammation is required to eliminate the invaders as early as possible. A delicate balance between inflammation and anti-inflammation is essential for lung homeostasis. A full understanding of the underlying mechanisms is vital in the treatment of patients with lung inflammation. This review focuses on cellular and molecular aspects of lung inflammation during acute and chronic inflammatory states.Keywords: inflammation, lung, inflammatory mediators, cytokines

  19. Cytotoxic T lymphocytes mediate chronic inflammation of the nasal mucosa of patients with atypical allergic rhinitis

    Directory of Open Access Journals (Sweden)

    Shuqi Qiu

    2011-01-01

    Full Text Available Background : The prevalence of chronic rhinitis is increasing rapidly; its pathogenesis is to be further understood; immune inflammation is one of the possible causative factors. Antigen specific CD8+ T cells play a critical role in the induction of chronic inflammation. Aims : This study aimed to investigate the role of antigen specific CD8+ T cells in the pathogenesis of chronic atypical allergic rhinitis. Material and Methods : Nasal mucosal epithelial surface scratching samples were obtained from patients with chronic obstruction atypical allergic rhinitis. Exosomes were purified from the scratching samples and examined by immune gold electron microscopy. The effect of exosomes on modulating dendritic cell′s properties, the effect of exosome-pulsed dendritic cells on naïve T cell differentiation and the antigen specific CD8+ T cell activation were observed by cell culture models. Results : Exosomes purified from patients with chronic atypical allergic rhinitis carried microbial products, Staphylococcal enterotoxin B (SEB, and airborne antigen, Derp1. Dendritic cells pulsed by SEB/Derp1-carrying exosomes showed high levels of CD80, CD86 and the major histocompatibility class I (MHCI. Exosome-pulsed dendritic cells could induce the naïve CD3+ T cells to differentiate into CD8+ T cells. Upon the exposure to a specific antigen, the CD8+ T cells released granzyme B and perforin; more than 30% antigen specific CD8+ T cells proliferated. Conclusions : Antigen specific CD8+ T cells play an important role in the pathogenesis of chronic obstruction atypical allergic rhinitis.

  20. Tracking of Inhaled Near-Infrared Fluorescent Nanoparticles in Lungs of SKH-1 Mice with Allergic Airway Inflammation.

    Science.gov (United States)

    Markus, M Andrea; Napp, Joanna; Behnke, Thomas; Mitkovski, Miso; Monecke, Sebastian; Dullin, Christian; Kilfeather, Stephen; Dressel, Ralf; Resch-Genger, Ute; Alves, Frauke

    2015-12-22

    Molecular imaging of inflammatory lung diseases, such as asthma, has been limited to date. The recruitment of innate immune cells to the airways is central to the inflammation process. This study exploits these cells for imaging purposes within the lung, using inhaled polystyrene nanoparticles loaded with the near-infrared fluorescence dye Itrybe (Itrybe-NPs). By means of in vivo and ex vivo fluorescence reflectance imaging of an ovalbumin-based allergic airway inflammation (AAI) model in hairless SKH-1 mice, we show that subsequent to intranasal application of Itrybe-NPs, AAI lungs display fluorescence intensities significantly higher than those in lungs of control mice for at least 24 h. Ex vivo immunofluorescence analysis of lung tissue demonstrates the uptake of Itrybe-NPs predominantly by CD68(+)CD11c(+)ECF-L(+)MHCII(low) cells, identifying them as alveolar M2 macrophages in the peribronchial and alveolar areas. The in vivo results were validated by confocal microscopy, overlapping tile analysis, and flow cytometry, showing an amount of Itrybe-NP-containing macrophages in lungs of AAI mice significantly larger than that in controls. A small percentage of NP-containing cells were identified as dendritic cells. Flow cytometry of tracheobronchial lymph nodes showed that Itrybe-NPs were negligible in lung draining lymph nodes 24 h after inhalation. This imaging approach may advance preclinical monitoring of AAI in vivo over time and aid the investigation of the role that macrophages play during lung inflammation. Furthermore, it allows for tracking of inhaled nanoparticles and can hence be utilized for studies of the fate of potential new nanotherapeutics.

  1. Gene Expression Profiling in Lungs of Chronic Asthmatic Mice Treated with Galectin-3: Downregulation of Inflammatory and Regulatory Genes

    Directory of Open Access Journals (Sweden)

    Esther López

    2011-01-01

    Full Text Available Background. Asthma is a disorder characterized by a predominance of Th2 cells and eosinophilic inflammation. Suppressors of cytokine signaling (SOCS proteins act as negative regulators of cytokine signaling. In particular, SOCS1 and SOCS3 play an important role in immune response by controlling the balance between Th1 and Th2 cells. In a previous study, we demonstrated that treatment of chronic asthmatic mice with gene therapy using plasmid encoding galectin-3 (Gal-3 led to an improvement in Th2 allergic inflammation. Methods. Using a microarray approach, this study endeavored to evaluate the changes produced by therapeutic Gal-3 delivered by gene therapy in a well-characterized mouse model of chronic airway inflammation. Results were confirmed by real-time RT-PCR, Western blot and immunohistochemical analysis. Results. We identify a set of genes involved in different pathways whose expression is coordinately decreased/increased in mice treated with Gal-3 gene therapy. We report a correlation between Gal-3 treatment and inhibition of SOCS1 and SOCS3 expression in lungs. Conclusion. These results suggest that negative regulation of SOCS1 and 3 following Gal-3 treatment could be a valuable therapeutic approach in allergic disease.

  2. Carbon nanoparticles induce ceramide- and lipid raft-dependent signalling in lung epithelial cells: a target for a preventive strategy against environmentally-induced lung inflammation

    Directory of Open Access Journals (Sweden)

    Peuschel Henrike

    2012-12-01

    Full Text Available Abstract Background Particulate air pollution in lung epithelial cells induces pathogenic endpoints like proliferation, apoptosis, and pro-inflammatory reactions. The activation of the epidermal growth factor receptor (EGFR is a key event responsible for signalling events involving mitogen activated protein kinases specific for these endpoints. The molecular events leading to receptor activation however are not well understood. These events are relevant for the toxicological evaluation of inhalable particles as well as for potential preventive strategies in situations when particulate air pollution cannot be avoided. The current study therefore had the objective to elucidate membrane-coupled events leading to EGFR activation and the subsequent signalling cascade in lung epithelial cells. Furthermore, we aimed to identify the molecular target of ectoine, a biophysical active substance which we described to prevent carbon nanoparticle-induced lung inflammation. Methods Membrane signalling events were investigated in isolated lipid rafts from lung epithelial cells with regard to lipid and protein content of the signalling platforms. Using positive and negative intervention approaches, lipid raft changes, subsequent signalling events, and lung inflammation were investigated in vitro in lung epithelial cells (RLE-6TN and in vivo in exposed animals. Results Carbon nanoparticle treatment specifically led to an accumulation of ceramides in lipid rafts. Detailed analyses demonstrated a causal link of ceramides and subsequent EGFR activation coupled with a loss of the receptor in the lipid raft fractions. In vitro and in vivo investigations demonstrate the relevance of these events for carbon nanoparticle-induced lung inflammation. Moreover, the compatible solute ectoine was able to prevent ceramide-mediated EGFR phosphorylation and subsequent signalling as well as lung inflammation in vivo. Conclusion The data identify a so far unknown event in pro

  3. Mechanical stress as the common denominator between chronic inflammation, cancer and Alzheimer’s disease

    Directory of Open Access Journals (Sweden)

    Marcel eLevy Nogueira

    2015-09-01

    Full Text Available The pathogenesis of common diseases such as Alzheimer’s disease (AD and cancer are currently poorly understood. Inflammation is a common risk factor for cancer and AD. Recent data, provided by our group and from others, demonstrate that increased pressure and inflammation are synonymous. There is a continuous increase in pressure from inflammation to fibrosis and then cancer. This in line with the numerous papers reporting high interstitial pressure in cancer. But most authors focus on the role of pressure in the lack of delivery of chemotherapy in the center of the tumor. Pressure may also be a key factor in carcinogenesis. Increased pressure is responsible for oncogene activation and cytokine secretion. Accumulation of mechanical stress plays a key role in the development of diseases of old age such as cardiomyopathy, atherosclerosis and osteoarthritis. Growing evidence suggest also a possible link between mechanical stress in the pathogenesis of AD. The aim of this review is to describe environmental and endogenous mechanical factors possibly playing a pivotal role in the mechanism of chronic inflammation, AD and cancer.

  4. The sickle cell mouse lung: proinflammatory and primed for allergic inflammation.

    Science.gov (United States)

    Andemariam, Biree; Adami, Alexander J; Singh, Anurag; McNamara, Jeffrey T; Secor, Eric R; Guernsey, Linda A; Thrall, Roger S

    2015-09-01

    Comorbid asthma in sickle cell disease (SCD) confers higher rates of vaso-occlusive pain and mortality, yet the physiological link between these two distinct diseases remains puzzling. We used a mouse model of SCD to study pulmonary immunology and physiology before and after the induction of allergic airway disease (AAD). SCD mice were sensitized with ovalbumin (OVA) and aluminum hydroxide by the intraperitoneal route followed by daily, nose-only OVA-aerosol challenge to induce AAD. The lungs of naive SCD mice showed signs of inflammatory and immune processes: (1) histologic and cytochemical evidence of airway inflammation compared with naive wild-type mice; (2) bronchoalveolar lavage (BAL) fluid contained increased total lymphocytes, %CD8+ T cells, granulocyte-colony stimulating factor, interleukin 5 (IL-5), IL-7, and chemokine (C-X-C motif) ligand (CXCL)1; and (3) lung tissue and hilar lymph node (HLN) had increased CD4+, CD8+, and regulatory T (Treg) cells. Furthermore, SCD mice at AAD demonstrated significant changes compared with the naive state: (1) BAL fluid with increased %CD4+ T cells and Treg cells, lower %CD8+ T cells, and decreased interferon gamma, CXCL10, chemokine (C-C motif) ligand 2, and IL-17; (2) serum with increased OVA-specific immunoglobulin E, IL-6, and IL-13, and decreased IL-1α and CXCL10; (3) no increase in Treg cells in the lung tissue or HLN; and (4) hyporesponsiveness to methacholine challenge. In conclusion, SCD mice have an altered immunologic pulmonary milieu and physiological responsiveness. These findings suggest that the clinical phenotype of AAD in SCD mice differs from that of wild-type mice and that individuals with SCD may also have a unique, divergent phenotype perhaps amenable to a different therapeutic approach. PMID:25843670

  5. Roles of Chronic Low-Grade Inflammation in the Development of Ectopic Fat Deposition

    Directory of Open Access Journals (Sweden)

    Lulu Liu

    2014-01-01

    Full Text Available Pattern of fat distribution is a major determinant for metabolic homeostasis. As a depot of energy, the storage of triglycerides in adipose tissue contributes to the normal fat distribution. Decreased capacity of fat storage in adipose tissue may result in ectopic fat deposition in nonadipose tissues such as liver, pancreas, and kidney. As a critical biomarker of metabolic complications, chronic low-grade inflammation may have the ability to affect the process of lipid accumulation and further lead to the disorder of fat distribution. In this review, we have collected the evidence linking inflammation with ectopic fat deposition to get a better understanding of the underlying mechanism, which may provide us with novel therapeutic strategies for metabolic disorders.

  6. Chronic obstructive pulmonary disease and obstructive sleep apnea: overlaps in pathophysiology, systemic inflammation, and cardiovascular disease.

    LENUS (Irish Health Repository)

    McNicholas, Walter T

    2012-02-01

    Chronic obstructive pulmonary disease (COPD) and obstructive sleep apnea syndrome represent two of the most prevalent chronic respiratory disorders in clinical practice, and cardiovascular diseases represent a major comorbidity in each disorder. The two disorders coexist (overlap syndrome) in approximately 1% of adults but asymptomatic lower airway obstruction together with sleep-disordered breathing is more prevalent. Although obstructive sleep apnea syndrome has similar prevalence in COPD as the general population, and vice versa, factors such as body mass index and smoking influence relationships. Nocturnal oxygen desaturation develops in COPD, independent of apnea\\/hypopnea, and is more severe in the overlap syndrome, thus predisposing to pulmonary hypertension. Furthermore, upper airway flow limitation contributes to nocturnal desaturation in COPD without apnea\\/hypopnea. Evidence of systemic inflammation in COPD and sleep apnea, involving C-reactive protein and IL-6, in addition to nuclear factor-kappaB-dependent pathways involving tumor necrosis factor-alpha and IL-8, provides insight into potential basic interactions between both disorders. Furthermore, oxidative stress develops in each disorder, in addition to activation and\\/or dysfunction of circulating leukocytes. These findings are clinically relevant because systemic inflammation may contribute to the pathogenesis of cardiovascular diseases and the cell\\/molecular pathways involved are similar to those identified in COPD and sleep apnea. However, the pathophysiological and clinical significance of systemic inflammation in COPD and sleep apnea is not proven, and thus, studies of patients with the overlap syndrome should provide insight into the mechanisms of systemic inflammation in COPD and sleep apnea, in addition to potential relationships with cardiovascular disease.

  7. Adipose tissue deficiency and chronic inflammation in diabetic Goto-Kakizaki rats.

    Directory of Open Access Journals (Sweden)

    Bai Xue

    Full Text Available Type 2 diabetes (T2DM is a heterogeneous group of diseases that is progressive and involves multiple tissues. Goto-Kakizaki (GK rats are a polygenic model with elevated blood glucose, peripheral insulin resistance, a non-obese phenotype, and exhibit many degenerative changes observed in human T2DM. As part of a systems analysis of disease progression in this animal model, this study characterized the contribution of adipose tissue to pathophysiology of the disease. We sacrificed subgroups of GK rats and appropriate controls at 4, 8, 12, 16 and 20 weeks of age and carried out a gene array analysis of white adipose tissue. We expanded our physiological analysis of the animals that accompanied our initial gene array study on the livers from these animals. The expanded analysis included adipose tissue weights, HbA1c, additional hormonal profiles, lipid profiles, differential blood cell counts, and food consumption. HbA1c progressively increased in the GK animals. Altered corticosterone, leptin, and adiponectin profiles were also documented in GK animals. Gene array analysis identified 412 genes that were differentially expressed in adipose tissue of GKs relative to controls. The GK animals exhibited an age-specific failure to accumulate body fat despite their relatively higher calorie consumption which was well supported by the altered expression of genes involved in adipogenesis and lipogenesis in the white adipose tissue of these animals, including Fasn, Acly, Kklf9, and Stat3. Systemic inflammation was reflected by chronically elevated white blood cell counts. Furthermore, chronic inflammation in adipose tissue was evident from the differential expression of genes involved in inflammatory responses and activation of natural immunity, including two interferon regulated genes, Ifit and Iipg, as well as MHC class II genes. This study demonstrates an age specific failure to accumulate adipose tissue in the GK rat and the presence of chronic

  8. Effect of Hedera helix on lung histopathology in chronic asthma.

    Directory of Open Access Journals (Sweden)

    Arzu Babayigit Hocaoglu

    2012-12-01

    Full Text Available Hedera helix  is widely used to treat bronchial asthma for many years. However, effects of this herb on lung histopathology is still far from clear. We aimed to determine the effect of oral administration of Hedera helix on lung histopathology in a murine model of chronic asthma.BALB/c  mice  were  divided  into  four  groups;   I  (Placebo,  II  (Hedera  helix, III (Dexamethasone and IV (Control. All mice except controls were sensitized and challenged with ovalbumin. Then, mice in group I received saline, group II 100 mg/kg Hedera helix and group III 1 mg/kg  dexamethasone via orogastic gavage once daily for one week. Airway histopathology was evaluated by using light and electron microscopy in all groups.Goblet  cell numbers and thicknesses of basement membrane were found  significantly lower in group II, but there was no statistically significant difference in terms of number of mast cells, thicknesses of epithelium and subepithelial smooth muscle layers between group I and II. When Hedera helix and dexamethasone groups were compared with each other, thickness of epithelium, subepithelial muscle layers, number of mast cells and goblet cells of group III were significantly ameliorated when compared with the group II.Although Hedera helix administration reduced only goblet cell counts and the thicknesses of basement membrane  in the  asthmatic airways, dexamethasone ameliorated all histopathologic parameters except thickness of  basement  membrane  better  than  Hedera helix.

  9. Lactobacillus rhamnosus GG reduces hepatic TNFα production and inflammation in chronic alcohol-induced liver injury.

    Science.gov (United States)

    Wang, Yuhua; Liu, Yanlong; Kirpich, Irina; Ma, Zhenhua; Wang, Cuiling; Zhang, Min; Suttles, Jill; McClain, Craig; Feng, Wenke

    2013-09-01

    The therapeutic effects of probiotic treatment in alcoholic liver disease (ALD) have been studied in both patients and experimental animal models. Although the precise mechanisms of the pathogenesis of ALD are not fully understood, gut-derived endotoxin has been postulated to play a crucial role in hepatic inflammation. Previous studies have demonstrated that probiotic therapy reduces circulating endotoxin derived from intestinal gram-negative bacteria in ALD. In this study, we investigated the effects of probiotics on hepatic tumor necrosis factor-α (TNFα) production and inflammation in response to chronic alcohol ingestion. Mice were fed Lieber DeCarli liquid diet containing 5% alcohol for 8weeks, and Lactobacillus rhamnosus GG (LGG) was supplemented in the last 2 weeks. Eight-week alcohol feeding caused a significant increase in hepatic inflammation as shown by histological assessment and hepatic tissue myeloperoxidase activity assay. Two weeks of LGG supplementation reduced hepatic inflammation and liver injury and markedly reduced TNFα expression. Alcohol feeding increased hepatic mRNA expression of Toll-like receptors (TLRs) and CYP2E1 and decreased nuclear factor erythroid 2-related factor 2 expression. LGG supplementation attenuated these changes. Using human peripheral blood monocytes-derived macrophages, we also demonstrated that incubation with ethanol primes both lipopolysaccharide- and flagellin-induced TNFα production, and LGG culture supernatant reduced this induction in a dose-dependent manner. In addition, LGG treatment also significantly decreased alcohol-induced phosphorylation of p38 MAP kinase. In conclusion, probiotic LGG treatment reduced alcohol-induced hepatic inflammation by attenuation of TNFα production via inhibition of TLR4- and TLR5-mediated endotoxin activation. PMID:23618528

  10. Leukocyte telomere length in major depression: correlations with chronicity, inflammation and oxidative stress--preliminary findings.

    Directory of Open Access Journals (Sweden)

    Owen M Wolkowitz

    Full Text Available BACKGROUND: Depression is associated with an unusually high rate of aging-related illnesses and early mortality. One aspect of "accelerated aging" in depression may be shortened leukocyte telomeres. When telomeres critically shorten, as often occurs with repeated mitoses or in response to oxidation and inflammation, cells may die. Indeed, leukocyte telomere shortening predicts early mortality and medical illnesses in non-depressed populations. We sought to determine if leukocyte telomeres are shortened in Major Depressive Disorder (MDD, whether this is a function of lifetime depression exposure and whether this is related to putative mediators, oxidation and inflammation. METHODOLOGY: Leukocyte telomere length was compared between 18 unmedicated MDD subjects and 17 controls and was correlated with lifetime depression chronicity and peripheral markers of oxidation (F2-isoprostane/Vitamin C ratio and inflammation (IL-6. Analyses were controlled for age and sex. PRINCIPAL FINDINGS: The depressed group, as a whole, did not differ from the controls in telomere length. However, telomere length was significantly inversely correlated with lifetime depression exposure, even after controlling for age (p<0.05. Average telomere length in the depressed subjects who were above the median of lifetime depression exposure (≥9.2 years' cumulative duration was 281 base pairs shorter than that in controls (p<0.05, corresponding to approximately seven years of "accelerated cell aging." Telomere length was inversely correlated with oxidative stress in the depressed subjects (p<0.01 and in the controls (p<0.05 and with inflammation in the depressed subjects (p<0.05. CONCLUSIONS: These preliminary data indicate that accelerated aging at the level of leukocyte telomeres is proportional to lifetime exposure to MDD. This might be related to cumulative exposure to oxidative stress and inflammation in MDD. This suggest that telomere shortening does not antedate depression

  11. Interaction between Chronic Inflammation and Oral HPV Infection in the Etiology of Head and Neck Cancers

    Directory of Open Access Journals (Sweden)

    Mine Tezal

    2012-01-01

    Full Text Available Incidences of oral tongue, base of the tongue, and tonsil cancers have been increasing steadily in many parts of the world in spite of declining rates of tobacco use over the last four decades. A better understanding of the etiology, interactions between risk factors, and new approaches to prevention and treatment are necessary to change this course. This paper will present evidence supporting a potential role of chronic inflammation in the etiologies of oral human papillomavirus infection and head and neck squamous cell carcinoma, and it will discuss the implications for prevention and treatment.

  12. Lower grade chronic inflammation is associated with obstructive sleep apnea syndrome in type 2 diabetes mellitus

    Institute of Scientific and Technical Information of China (English)

    朱宏霞

    2014-01-01

    Objective To investigate whether the existence of obstructive sleep apnea syndrome(OSAS)in patients with type 2 diabetes(T2DM) is associated with low grade chronic inflammation.Methods Fifty-four patients hospitalized for poor glycemic control from 12/2008 to 12/2009 were divided into 2 groups,OSAS group(T2DM with OSAS,27 cases)and NOSAS group(T2DM without OSAS,27 cases).The control group consisted of 26people from a health check-up program without diabetes

  13. Chronic obstructive lung disease and posttraumatic stress disorder: current perspectives

    Directory of Open Access Journals (Sweden)

    Abrams TE

    2015-10-01

    Full Text Available Thad E Abrams,1,2 Amy Blevins,1,3 Mark W Vander Weg1,2,4 1Department of Internal Medicine, University of Iowa, 2Center for Comprehensive Access and Delivery Research and Evaluation, Iowa City VA Health Care System, 3Hardin Health Sciences Library, 4Department of Psychological and Brain Sciences, University of Iowa, Iowa City, IA, USA Background: Several studies have reported on the co-occurrence of chronic obstructive pulmonary disease (COPD and psychiatric conditions, with the most robust evidence base demonstrating an impact of comorbid anxiety and depression on COPD-related outcomes. In recent years, research has sought to determine if there is a co-occurrence between COPD and posttraumatic stress disorder (PTSD as well as for associations between PTSD and COPD-related outcomes. To date, there have been no published reviews summarizing this emerging literature.Objectives: The primary objective of this review was to determine if there is adequate evidence to support a co-occurrence between PTSD and COPD. Secondary objectives were to: 1 determine if there are important clinical considerations regarding the impact of PTSD on COPD management, and 2 identify targeted areas for further research.Methods: A structured review was performed using a systematic search strategy limited to studies in English, addressing adults, and to articles that examined: 1 the co-occurrence of COPD and PTSD and 2 the impact of PTSD on COPD-related outcomes. To be included, articles must have addressed some type of nonreversible obstructive lung pathology.Results: A total of 598 articles were identified for initial review. Upon applying the inclusion and exclusion criteria, n=19 articles or abstracts addressed our stated objectives. Overall, there is inconclusive evidence to support the co-occurrence between PTSD and COPD. Studies finding a significant co-occurrence generally had inferior methods of identifying COPD; in contrast, studies that utilized more robust COPD

  14. Allergen-Experienced Group 2 Innate Lymphoid Cells Acquire Memory-like Properties and Enhance Allergic Lung Inflammation.

    Science.gov (United States)

    Martinez-Gonzalez, Itziar; Mathä, Laura; Steer, Catherine A; Ghaedi, Maryam; Poon, Grace F T; Takei, Fumio

    2016-07-19

    Group 2 innate lymphoid cells (ILC2s) in the lung are stimulated by inhaled allergens. ILC2s do not directly recognize allergens but they are stimulated by cytokines including interleukin (IL)-33 released by damaged epithelium. In response to allergens, lung ILC2s produce T helper 2 cell type cytokines inducing T cell-independent allergic lung inflammation. Here we examined the fate of lung ILC2s upon allergen challenges. ILC2s proliferated and secreted cytokines upon initial stimulation with allergen or IL-33, and this phase was followed by a contraction phase as cytokine production ceased. Some ILC2s persisted long after the resolution of the inflammation as allergen-experienced ILC2s and responded to unrelated allergens more potently than naive ILC2s, mediating severe allergic inflammation. The allergen-experienced ILC2s exhibited a gene expression profile similar to that of memory T cells. The memory-like properties of allergen-experienced ILC2s may explain why asthma patients are often sensitized to multiple allergens. PMID:27421705

  15. Serum concentrations of GM-CSF and G-CSF correlate with the Th1/Th2 cytokine response in cystic fibrosis patients with chronic Pseudomonas aeruginosa lung infection

    DEFF Research Database (Denmark)

    Moser, Claus; Jensen, Peter Ø; Pressler, Tacjana;

    2005-01-01

    The inflammation in cystic fibrosis (CF) patients with chronic Pseudomonas aeruginosa lung infection is dominated by polymorphonuclear neutrophils (PMNs). There seems to be a relationship between the PMN-dominated inflammation, pronounced antibody production and a Th2-dominated response. Apart from...... lung function. In addition, an inverse correlation between IL-3 and IFN-gamma was observed. The results indicate involvement of endogenous GM-CSF, G-CSF and IL-3 in the skewed Th response in CF, and change to a Th1-dominated response might be achieved with GM-CSF treatment....

  16. Mast cell stabilization alleviates acute lung injury after orthotopic autologous liver transplantation in rats by downregulating inflammation.

    Directory of Open Access Journals (Sweden)

    Ailan Zhang

    Full Text Available BACKGROUND: Acute lung injury (ALI is one of the most severe complications after orthotopic liver transplantation. Amplified inflammatory response after transplantation contributes to the process of ALI, but the mechanism underlying inflammation activation is not completely understood. We have demonstrated that mast cell stabilization attenuated inflammation and ALI in a rodent intestine ischemia/reperfusion model. We hypothesized that upregulation of inflammation triggered by mast cell activation may be involve in ALI after liver transplantation. METHODS: Adult male Sprague-Dawley rats received orthotopic autologous liver transplantation (OALT and were executed 4, 8, 16, and 24 h after OALT. The rats were pretreated with the mast cell stabilizers cromolyn sodium or ketotifen 15 min before OALT and executed 8 h after OALT. Lung tissues and arterial blood were collected to evaluate lung injury. β-hexosaminidase and mast cell tryptase levels were assessed to determine the activation of mast cells. Tumor necrosis factor α (TNF-α, interleukin (IL-1β and IL-6 in serum and lung tissue were analyzed by enzyme-linked immunosorbent assay. Nuclear factor-kappa B (NF-κB p65 translocation was assessed by Western blot. RESULTS: The rats that underwent OALT exhibited severe pulmonary damage with a high wet-to-dry ratio, low partial pressure of oxygen, and low precursor surfactant protein C levels, which corresponded to the significant elevation of pro-inflammatory cytokines, β-hexosaminidase, and tryptase levels in serum and lung tissues. The severity of ALI progressed and maximized 8 h after OALT. Mast cell stabilization significantly inhibited the activation of mast cells, downregulated pro-inflammatory cytokine levels and translocation of NF-κB, and attenuated OALT-induced ALI. CONCLUSIONS: Mast cell activation amplified inflammation and played an important role in the process of post-OALT related ALI.

  17. Current concepts in chronic inflammatory diseases: Interactions between microbes, cellular metabolism, and inflammation.

    Science.gov (United States)

    Garn, Holger; Bahn, Sabine; Baune, Bernhard T; Binder, Elisabeth B; Bisgaard, Hans; Chatila, Talal A; Chavakis, Triantafyllos; Culmsee, Carsten; Dannlowski, Udo; Gay, Steffen; Gern, James; Haahtela, Tari; Kircher, Tilo; Müller-Ladner, Ulf; Neurath, Markus F; Preissner, Klaus T; Reinhardt, Christoph; Rook, Graham; Russell, Shannon; Schmeck, Bernd; Stappenbeck, Thaddeus; Steinhoff, Ulrich; van Os, Jim; Weiss, Scott; Zemlin, Michael; Renz, Harald

    2016-07-01

    Recent research indicates that chronic inflammatory diseases, including allergies and autoimmune and neuropsychiatric diseases, share common pathways of cellular and molecular dysregulation. It was the aim of the International von-Behring-Röntgen Symposium (October 16-18, 2014, in Marburg, Germany) to discuss recent developments in this field. These include a concept of biodiversity; the contribution of urbanization, lifestyle factors, and nutrition (eg, vitamin D); and new mechanisms of metabolic and immune dysregulation, such as extracellular and intracellular RNAs and cellular and mitochondrial stress. Epigenetic mechanisms contribute further to altered gene expression and therefore to the development of chronic inflammation. These novel findings provide the foundation for further development of preventive and therapeutic strategies. PMID:27373325

  18. Aseptic tissue necrosis and chronic inflammation after irrigation of penetrating hand wounds using Octenisept®.

    Science.gov (United States)

    Franz, T; Vögelin, E

    2012-01-01

    Penetrating hand wounds are common and these are managed by thorough debridement. However, stab wounds without evidence of divided structures are often treated with irrigation using antiseptic substances, antibiotic therapy, and immobilization. Octenisept® (Schülke & Mayr Ltd) is a widely used antiseptic agent for disinfection of acute or chronic wounds. It has a broad spectrum of antiseptic efficacy and has become an antiseptic of first choice in many hospitals. Within a few months, four patients presented to us with chronic inflammation and severe tissue necrosis after irrigation of penetrating hand wounds with Octenisept®. Repeated surgery and debridement was required in all patients. Wound healing was prolonged and patients had persisting oedema. Penetrating hand wounds must not be irrigated with Octenisept®.

  19. Apios americana Medik Extract Alleviates Lung Inflammation in Influenza Virus H1N1- and Endotoxin-Induced Acute Lung Injury.

    Science.gov (United States)

    Sohn, Sung-Hwa; Lee, Sang-Yeon; Cui, Jun; Jang, Ho Hee; Kang, Tae-Hoon; Kim, Jong-Keun; Kim, In-Kyoung; Lee, Deuk-Ki; Choi, Seulgi; Yoon, Il-Sub; Chung, Ji-Woo; Nam, Jae-Hwan

    2015-12-28

    Apios americana Medik (hereinafter Apios) has been reported to treat diseases, including cancer, hypertension, obesity, and diabetes. The therapeutic effect of Apios is likely to be associated with its anti-inflammatory activity. This study was conducted to evaluate the protective effects of Apios in animal models of acute lung injury induced by lipopolysaccharide (LPS) or pandemic H1N1 2009 influenza A virus (H1N1). Mice were exposed to LPS or H1N1 for 2-4 days to induce acute lung injury. The treatment groups were administered Apios extracts via oral injection for 8 weeks before LPS treatment or H1N1 infection. To investigate the effects of Apios, we assessed the mice for in vivo effects of Apios on immune cell infiltration and the level of pro-inflammatory cytokines in the bronchoalveolar lavage (BAL) fluid, and histopathological changes in the lung. After induction of acute lung injury, the numbers of neutrophils and total cells were lower in the Apios-treated groups than in the non-Apios-treated LPS and H1N1 groups. The Apios groups tended to have lower levels of tumor necrosis factor-a and interleukin-6 in BAL fluid. In addition, the histopathological changes in the lungs were markedly reduced in the Apios-treated groups. These data suggest that Apios treatment reduces LPS- and H1N1-induced lung inflammation. These protective effects of Apios suggest that it may have therapeutic potential in acute lung injury.

  20. Mechanical properties and reactivity of vessels in isolated perfused lungs of chronically hypoxic rats.

    Science.gov (United States)

    Emery, C J; Bee, D; Barer, G R

    1981-11-01

    1. Chronically hypoxic rats kept in 10% (v/v) O2 for 3--6 weeks, were compared with littermate control rats. Pulmonary vascular resistance, measured from the slope of the pressure-flow relationship in isolated lungs perfused with blood of normal packed cell volume was higher in chronically hypoxic than control rats even during normoxia. 2. Chronically hypoxic rats weighed less than control rats but their pulmonary vascular volume, measured with labelled albumin was similar to control rats. This, together with evidence that the number of precapillary vessels is not reduced, does not suggest a large reduction in the vascular bed in chronic hypoxia. 3. A greater vasodilator action of isoprenaline and adenosine in chronically hypoxic than control lungs suggested a higher normoxic vascular tone. This higher tone was not the sole cause of increased resistance in chronically hypoxic lungs, since maximal vasodilatation did not reduce resistance to control levels. The chief cause was probably encroachment of new muscle on the vascular lumen of small vessels. 4. Pulmonary arterial compliance was reduced in chronically hypoxic lungs. 5. Reactivity of vessels to ventilation hypoxia, over a wide range of oxygen tension, to angiotensin II (ANG II) and to adenosine 5'-triphosphate (ATP) was significantly greater in chronically hypoxic than control lungs, but thresholds to these stimuli were not reduced. PMID:7285503

  1. Topical administration of hyaluronic acid in children with recurrent or chronic middle ear inflammations.

    Science.gov (United States)

    Torretta, Sara; Marchisio, Paola; Rinaldi, Vittorio; Gaffuri, Michele; Pascariello, Carla; Drago, Lorenzo; Baggi, Elena; Pignataro, Lorenzo

    2016-09-01

    Hyaluronic acid (HA) treatment has been successfully performed in patients with recurrent upper airway infections or rhinitis. The aim of this study was to assess the efficacy and safety of the topical nasal administration of an HA-based compound by investigating its effects in children with recurrent or chronic middle ear inflammations and chronic adenoiditis. A prospective, single-blind, 1:1 randomised controlled study was performed to compare otoscopy, tympanometry and pure-tone audiometry in children which received the daily topical administration of normal 0.9% sodium chloride saline solution (control group) or 9 mg of sodium hyaluronate in 3 mL of a 0.9% sodium saline solution. The final analysis was based on 116 children (49.1% boys; mean age, 62.9 ± 17.9 months): 58 in the control group and 58 in the study group. At the end of follow-up, the prevalence of patients with impaired otoscopy was significantly lower in the study group (P value = 0.024) compared to baseline but not in the control group. In comparison with baseline, the prevalence of patients with impaired tympanometry at the end of the follow-up period was significantly lower in the study group (P value = 0.047) but not in the control group. The reduction in the prevalence of patients with conductive hearing loss (CHL) (P value = 0.008) and those with moderate CHL (P value = 0.048) was significant in the study group, but not in the control group. The mean auditory threshold had also significantly improved by the end of treatment in the study group (P value = 0.004) but not in the control group. Our findings confirm the safety of intermittent treatment with a topical nasal sodium hyaluronate solution and are the first to document its beneficial effect on clinical and audiological outcomes in children with recurrent or chronic middle ear inflammations associated with chronic adenoiditis. PMID:27481884

  2. Human umbilical cord mesenchymal stem cells reduce systemic inflammation and attenuate LPS-induced acute lung injury in rats

    Directory of Open Access Journals (Sweden)

    Li Jianjun

    2012-09-01

    Full Text Available Abstract Background Mesenchymal stem cells (MSCs possess potent immunomodulatory properties and simultaneously lack the ability to illicit immune responses. Hence, MSCs have emerged as a promising candidate for cellular therapeutics for inflammatory diseases. Within the context of this study, we investigated whether human umbilical cord-derived mesenchymal stem cells (UC-MSCs could ameliorate lipopolysaccharide- (LPS- induced acute lung injury (ALI in a rat model. Methods ALI was induced via injection of LPS. Rats were divided into three groups: (1 saline group(control, (2 LPS group, and (3 MSC + LPS group. The rats were sacrificed at 6, 24, and 48 hours after injection. Serum, bronchoalveolar lavage fluid (BALF, and lungs were collected for cytokine concentration measurements, assessment of lung injury, and histology. Results UC-MSCs increased survival rate and suppressed LPS-induced increase of serum concentrations of pro-inflammatory mediators TNF-α, IL-1β, and IL-6 without decreasing the level of anti-inflammatory cytokine IL-10. The MSC + LPS group exhibited significant improvements in lung inflammation, injury, edema, lung wet/dry ratio, protein concentration, and neutrophil counts in the BALF, as well as improved myeloperoxidase (MPO activity in the lung tissue. Furthermore, UC-MSCs decreased malondialdehyde (MDA production and increased Heme Oxygenase-1 (HO-1 protein production and activity in the lung tissue. Conclusion UC-MSCs noticeably increased the survival rate of rats suffering from LPS-induced lung injury and significantly reduced systemic and pulmonary inflammation. Promoting anti-inflammatory homeostasis and reducing oxidative stress might be the therapeutic basis of UC-MSCs.

  3. Cavitating Lung Lesions in Chronic Thromboembolic Pulmonary Hypertension

    Directory of Open Access Journals (Sweden)

    edwin j r van beek

    2008-09-01

    Full Text Available Purpose: The aim of this study is to assess the incidence and natural history of cavitating lung lesions in chronic thromboembolic pulmonary hypertension (CTEPH, note thrombus position between patients with and without a cavity and determine whether their development is a predictor of mortality. Materials & Methods: All patients with confirmed CTEPH attending our Pulmonary Vascular Unit between February 1998 and January 2006 were identified, and a review of their notes and imaging was performed. Thrombus position, pre-disposing factors, cavity progression and mortality were noted, and comparisons made between those with and without a cavity. Results: 11 of 104 patients had a cavity (10.6%. Thrombus distribution was similar between those with and those without a cavity. Preceding infection was not proven in  most cases. 27.3% of patients with a cavity died compared to 26.8% of those without. Conclusion: Cavity formation in CTEPH is 3 times more common than in acute pulmonary embolism. Thrombus position does not predict cavity development, and the presence of a cavity may serve as an indicator of disease severity but does not appear to predict mortality.

  4. Bilateral vagotomy or atropine pre-treatment reduces experimental diesel-soot induced lung inflammation

    International Nuclear Information System (INIS)

    To investigate the role of the vagus nerve in acute inflammatory and cardiorespiratory responses to diesel particulate (DP) in the rat airway, we measured changes in respiration, blood pressure and neutrophils in lungs of urethane anesthetized Wistar rats 6-h post-instillation of DP (500 μg) and studied the effect of mid-cervical vagotomy or atropine (1 mg kg-1) pre-treatment. In conscious rats, we investigated DP, with and without atropine pre-treatment. DP increased neutrophil level in BAL (bronchoalveolar lavage) fluid from intact anesthetized rats to 2.5 ± 0.7 x 106 cells (n = 8), compared with saline instillation (0.3 ± 0.1 x 106, n = 7; P 6 cells (n = 8; P 6 (n = 4; P 6, n = 4, was reduced by pre-treatment with atropine to 2.2 ± 1.2 x 106 cells, n = 3. Hyperventilation occurred 6 h after DP in anesthetized rats with intact vagi, but not in bilaterally vagotomized or atropine pre-treated animals and was abolished by vagotomy (P < 0.05, paired test). There were no significant differences in the other variables (mean blood pressure, heart rate and heart rate variability) measured before and 360 min after DP. In conclusion, DP activates a pro-inflammatory vago-vagal reflex which is reduced by atropine. Muscarinic ACh receptors in the rat lung are involved in DP-induced neutrophilia, and hence muscarinic antagonists may reduce airway and/or cardiovascular inflammation evoked by inhaled atmospheric DP in susceptible individuals

  5. SHIP represses lung inflammation and inhibits mammary tumor metastasis in BALB/c mice

    Science.gov (United States)

    Hamilton, Melisa J.; Halvorsen, Elizabeth C.; LePard, Nancy E.; Bosiljcic, Momir; Ho, Victor W.; Lam, Vivian; Banáth, Judit

    2016-01-01

    SH2-containing-inositol-5′-phosphatase (SHIP) is a negative regulator of the phosphatidylinositol-3-kinase pathway in hematopoietic cells and limits the development of leukemias and lymphomas. The potential role of SHIP in solid tumor development and metastasis remains unknown. While SHIP restricts the aberrant development of myeloid cells in C57BL/6 mice, there are conflicting reports regarding the effect of SHIP deletion in BALB/c mice with important consequences for determining the influence of SHIP in different model tumor systems. We generated SHIP−/− BALB/c mice and challenged them with syngeneic non-metastatic 67NR or metastatic 4T1 mammary tumors. We demonstrate that SHIP restricts the development, alternative-activation, and immunosuppressive function of myeloid cells in tumor-free and tumor-bearing BALB/c mice. Tumor-free SHIP−/− BALB/c mice exhibited pulmonary inflammation, myeloid hyperplasia, and M2-polarized macrophages and this phenotype was greatly exacerbated by 4T1, but not 67NR, tumors. 4T1-bearing SHIP−/− mice rapidly lost weight and died from necrohemorrhagic inflammatory pulmonary disease, characterized by massive infiltration of pulmonary macrophages and myeloid-derived suppressor cells that were more M2-polarized and immunosuppressive than wild-type cells. Importantly, while SHIP loss did not affect primary tumor growth, 4T1-bearing SHIP−/− mice had 7.5-fold more metastatic tumor cells in their lungs than wild-type mice, consistent with the influence of immunosuppressive myeloid cells on metastatic growth. Our findings identify the hematopoietic cell-restricted protein SHIP as an intriguing target to influence the development of solid tumor metastases, and support development of SHIP agonists to prevent the accumulation of immunosuppressive myeloid cells and tumor metastases in the lungs to improve treatment of metastatic breast cancer. PMID:26683227

  6. Cigarette smoke worsens lung inflammation and impairs resolution of influenza infection in mice

    Directory of Open Access Journals (Sweden)

    Jones Jessica E

    2008-07-01

    Full Text Available Abstract Background Cigarette smoke has both pro-inflammatory and immunosuppressive effects. Both active and passive cigarette smoke exposure are linked to an increased incidence and severity of respiratory virus infections, but underlying mechanisms are not well defined. We hypothesized, based on prior gene expression profiling studies, that upregulation of pro-inflammatory mediators by short term smoke exposure would be protective against a subsequent influenza infection. Methods BALB/c mice were subjected to whole body smoke exposure with 9 cigarettes/day for 4 days. Mice were then infected with influenza A (H3N1, Mem71 strain, and analyzed 3 and 10 days later (d3, d10. These time points are the peak and resolution (respectively of influenza infection. Results Inflammatory cell influx into the bronchoalveolar lavage (BALF, inflammatory mediators, proteases, histopathology, viral titres and T lymphocyte profiles were analyzed. Compared to smoke or influenza alone, mice exposed to smoke and then influenza had more macrophages, neutrophils and total lymphocytes in BALF at d3, more macrophages in BALF at d10, lower net gelatinase activity and increased activity of tissue inhibitor of metalloprotease-1 in BALF at d3, altered profiles of key cytokines and CD4+ and CD8+ T lymphocytes, worse lung pathology and more virus-specific, activated CD8+ T lymphocytes in BALF. Mice smoke exposed before influenza infection had close to 10-fold higher lung virus titres at d3 than influenza alone mice, although all mice had cleared virus by d10, regardless of smoke exposure. Smoke exposure caused temporary weight loss and when smoking ceased after viral infection, smoke and influenza mice regained significantly less weight than smoke alone mice. Conclusion Smoke induced inflammation does not protect against influenza infection. In most respects, smoke exposure worsened the host response to influenza. This animal model may be useful in studying how smoke worsens

  7. Periodontal Disease: A Covert Source of Inflammation in Chronic Kidney Disease Patients

    Directory of Open Access Journals (Sweden)

    Gener Ismail

    2013-01-01

    Full Text Available The prevalence of atherosclerotic complications (myocardial infarction, stroke, and sudden death is increased in end-stage renal disease (ESRD patients, especially in haemodialysis patients. Increasing evidence suggests that both in general population and in dialysis patients, systemic inflammation plays a dominant role in the pathogenesis of atherosclerotic complications. In general population, also, evidence shows that moderate to severe periodontitis can contribute to inflammatory burden by increasing serum CRP levels and may increase the prevalence of atherosclerotic events. Moreover, the results of some new interventional studies reveal that effective phase I periodontal therapy may decrease serum CRP levels, the most important acute phase protein, monitored as a systemic marker of inflammation and endothelial dysfunction as well, used as an initial predictor of atherosclerotic events. Considering that moderate to severe periodontal diseases have a higher prevalence in CKD and in dialysis population and that periodontal examination is not part of the standard medical assessment, destructive periodontitis might be an ignored source of systemic inflammation in end-stage renal disease patients and may add to the chronic inflammatory status in CKD.

  8. Method of diagnosis of chronic non-specific diseases of lungs in children

    International Nuclear Information System (INIS)

    Method of diagnosis of chronic nonspecific diseases of lungs in children using bronchography and arteriography is suggested to improve diagnosis accuracy. The method lies in simultaneous contrasting of all bronchial arteries of both lungs. The suggested method of diagnosis enabled to obtain data on pathology of bronchial arteries and bronchial structurs, to reveal additional information about propogation and character of pathologic process

  9. A Dynamic Bronchial Airway Gene Expression Signature of Chronic Obstructive Pulmonary Disease and Lung Function Impairment

    NARCIS (Netherlands)

    Steiling, Katrina; van den Berge, Maarten; Hijazi, Kahkeshan; Florido, Roberta; Campbell, Joshua; Liu, Gang; Xiao, Ji; Zhang, Xiaohui; Duclos, Grant; Drizik, Eduard; Si, Huiqing; Perdomo, Catalina; Dumont, Charles; Coxson, Harvey O.; Alekseyev, Yuriy O.; Sin, Don; Pare, Peter; Hogg, James C.; McWilliams, Annette; Hiemstra, Pieter S.; Sterk, Peter J.; Timens, Wim; Chang, Jeffrey T.; Sebastiani, Paola; O'Connor, George T.; Bild, Andrea H.; Postma, Dirkje S.; Lam, Stephen; Spira, Avrum; Lenburg, Marc E.

    2013-01-01

    Rationale Molecular phenotyping of chronic obstructive pulmonary disease (COPD) has been impeded in part by the difficulty in obtaining lung tissue samples from individuals with impaired lung function. Objectives: We sought to determine whether COPD-associated processes are reflected in gene express

  10. Dexamethasone treatment does not inhibit fibroproliferation in chronic lung disease of prematurity

    NARCIS (Netherlands)

    W.A. Dik (Willem); M.A. Versnel (Marjan); B.A. Naber (Brigitta); D.J. Janssen; A.H. van Kaam; L.J.I. Zimmermann (Luc)

    2003-01-01

    textabstractPulmonary fibrosis results from excessive fibroblast proliferation and increased collagen deposition and occurs in chronic lung disease of prematurity (CLD). Platelet-derived growth factor (PDGF)-BB is mitogenic for fibroblasts and levels are increased in fibrotic lung

  11. Sudden cardiac arrest in a patient with epilepsy induced by chronic inflammation on the cerebral surface

    Institute of Scientific and Technical Information of China (English)

    Yuxi Liu; Weicheng Hao; Xiaoming Yang; Yimin Wang; Yu Su

    2012-01-01

    The present study analyzed a patient with epilepsy due to chronic inflammation on the cerebral surface underwent sudden cardiac arrest. Paradoxical brain discharge, which occurred prior to epileptic seizures, induced a sudden cardiac arrest. However, when the focal brain pressure was relieved, cardiac arrest disappeared. A 27-year-old male patient underwent pre-surgical video-electroencephalogram monitoring for 160 hours. During monitoring, secondary tonic-clonic seizures occurred five times. A burst of paradoxical brain discharges occurred at 2-19 seconds (mean 8 seconds) prior to epileptic seizures. After 2-3 seconds, sudden cardiac arrest occurred and lasted for 12-22 seconds (average 16 seconds). The heart rate subsequently returned to a normal rate. Results revealed arachnoid pachymenia and adhesions, as well as mucus on the focal cerebral surface, combined with poor circulation and increased pressure. Intracranial electrodes were placed using surgical methods. Following removal of the arachnoid adhesions and mucus on the local cerebral surface, paradoxical brain discharge and epileptic seizures occurred three times, but sudden cardiac arrest was not recorded during 150-hour monitoring. Post-surgical histological examination indicated meningitis. Experimental findings suggested that paradoxical brain discharge led to cardiac arrest instead of epileptic seizures; the insult was associated with chronic inflammation on the cerebral surface, which subsequently led to hypertension and poor blood circulation in focal cerebral areas.

  12. IL-32: A Novel Pluripotent Inflammatory Interleukin, towards Gastric Inflammation, Gastric Cancer, and Chronic Rhino Sinusitis

    Directory of Open Access Journals (Sweden)

    Muhammad Babar Khawar

    2016-01-01

    Full Text Available A vast variety of nonstructural proteins have been studied for their key roles and involvement in a number of biological phenomenona. Interleukin-32 is a novel cytokine whose presence has been confirmed in most of the mammals except rodents. The IL-32 gene was identified on human chromosome 16 p13.3. The gene has eight exons and nine splice variants, namely, IL-32α, IL-32β, IL-32γ, IL-32δ, IL-32ε, IL-32ζ, IL-32η, IL-32θ, and IL-32s. It was found to induce the expression of various inflammatory cytokines including TNF-α, IL-6, and IL-1β as well as macrophage inflammatory protein-2 (MIP-2 and has been reported previously to be involved in the pathogenesis and progression of a number of inflammatory disorders, namely, inflammatory bowel disease (IBD, gastric inflammation and cancer, rheumatoid arthritis, and chronic obstructive pulmonary disease (COPD. In the current review, we have highlighted the involvement of IL-32 in gastric cancer, gastric inflammation, and chronic rhinosinusitis. We have also tried to explore various mechanisms suspected to induce the expression of this extraordinary cytokine as well as various mechanisms of action employed by IL-32 during the mediation and progression of the above said problems.

  13. Inflammation as a Risk of Developing Chronic Kidney Disease in Rheumatoid Arthritis

    Science.gov (United States)

    Kochi, Masako; Kohagura, Kentaro; Shiohira, Yoshiki; Iseki, Kunitoshi; Ohya, Yusuke

    2016-01-01

    Objective The relationship between chronic inflammation and the incidence of chronic kidney disease (CKD) remained not-clear in patients with rheumatoid arthritis (RA). This study aims to examine the relationship between persistently high C-reactive protein (CRP), a marker of inflammation, and the incidence of CKD in RA. Methods We retrospectively examined the relationship between the levels of CRP and incidence of CKD in 345 RA patients. The outcome of interest was incidence of CKD, defined as an estimated glomerular filtration rate (eGFR) CRP, as >3.0 mg/L. On the basis of three measurements of CRP for 6-months period, patients were divided into three groups: group 1, including patients with no high CRP values; group 2, patients with transient high CRP values (once or twice) and group 3, patients with persistently high CRP values. Results During a median follow-up period of 89 months, 14% of all patients developed CKD. The cumulative incidence of CKD was 7% in group 1, 14% in group 2 and 22% in group 3 (P = 0.008, log-rank test). In a multivariate analysis, including classical risk factors for CKD, persistently high CRP was an independent predictor of the incidence of CKD (hazard ratio, 3.00; 95% confidence interval, 1.23–8.53; P = 0.01). Conclusions Persistently high CRP was a significant risk factor for the incidence of CKD. Results suggest that persistent inflammation is a marker for the high risk of CKD in RA. PMID:27537204

  14. Mouse lung inflammation after instillation of particulate matter collected from a working dairy barn

    International Nuclear Information System (INIS)

    Coarse and fine particulate matter (PM2.5-10 and PM2.5, respectively) are regulated ambient air pollutants thought to have major adverse health effects in exposed humans. The role of endotoxin and other bioaerosol components in the toxicity of PM from ambient air is controversial. This study evaluated the inflammatory lung response in mice instilled intratracheally with PM2.5-10 and PM2.5 emitted from a working dairy barn, a source presumed to have elevated concentrations of endotoxin. PM2.5-10 was more pro-inflammatory on an equal weight basis than was PM2.5; both fractions elicited a predominantly neutrophilic response. The inflammatory response was reversible, with a peak response to PM2.5-10 observed at 24 h after instillation, and a return to control values by 72 h after instillation. The major active pro-inflammatory component in whole PM2.5-10, but not in whole PM2.5, is heat-labile, consistent with it being endotoxin. A heat treatment protocol for the gradual inactivation of biological materials in the PM fractions over a measurable time course was developed and optimized in this study using pure lipopolysaccharide (LPS) as a model system. The time course of heat inactivation of pure LPS and of endotoxin activity in PM2.5-10 as measured by Limulus bioassay is identical. The active material in both PM2.5-10 and PM2.5 remained in the insoluble fraction when the whole PM samples were extracted with physiological saline solution. Histological analysis of lung sections from mice instilled with PM2.5-10 or PM2.5 showed evidence of inflammation consistent with the cellular responses observed in lung lavage fluid. The major pro-inflammatory components present in endotoxin-rich PM were found in the insoluble fraction of PM2.5-10; however, in contrast with PM2.5-10 isolated from ambient air in the Central Valley of California, the active components in the insoluble fraction were heat-labile.

  15. The Changes of Energy Interactions between Nucleus Function and Mitochondria Functions Causing Transmutation of Chronic Inflammation into Cancer Metabolism.

    Science.gov (United States)

    Ponizovskiy, Michail R

    2016-01-01

    Interactions between nucleus and mitochondria functions induce the mechanism of maintenance stability of cellular internal energy according to the first law of thermodynamics in able-bodied cells and changes the mechanisms of maintenance stability of cellular internal energy creating a transition stationary state of ablebodied cells into quasi-stationary pathologic states of acute inflammation transiting then into chronic inflammation and then transmuting into cancer metabolism. The mechanisms' influences of intruding etiologic pathologic agents (microbe, virus, etc.) lead to these changes of energy interactions between nucleus and mitochondria functions causing general acute inflammation, then passing into local chronic inflammation, and reversing into cancer metabolism transmutation. Interactions between biochemical processes and biophysical processes of cellular capacitors' operations create a supplementary mechanism of maintenance stability of cellular internal energy in the norm and in pathology. Discussion of some scientific works eliminates doubts of the authors of these works. PMID:27480780

  16. Vagus Nerve through α7 nAChR Modulates Lung Infection and Inflammation: Models, Cells, and Signals

    Directory of Open Access Journals (Sweden)

    Haiya Wu

    2014-01-01

    Full Text Available Cholinergic anti-inflammatory pathway (CAP bridges immune and nervous systems and plays pleiotropic roles in modulating inflammation in animal models by targeting different immune, proinflammatory, epithelial, endothelial, stem, and progenitor cells and signaling pathways. Acute lung injury (ALI is a devastating inflammatory disease. It is pathogenically heterogeneous and involves many cells and signaling pathways. Here, we emphasized the research regarding the modulatory effects of CAP on animal models, cell population, and signaling pathways that involved in the pathogenesis of ALI. By comparing the differential effects of CAP on systemic and pulmonary inflammation, we postulated that a pulmonary parasympathetic inflammatory reflex is formed to sense and respond to pathogens in the lung. Work targeting the formation and function of pulmonary parasympathetic inflammatory reflex would extend our understanding of how vagus nerve senses, recognizes, and fights with pathogens and inflammatory responses.

  17. Elevated plasma levels of pigment epithelium-derived factor correlated with inflammation and lung function in COPD patients

    Directory of Open Access Journals (Sweden)

    Li X

    2015-03-01

    diagnose COPD patients and we also analyzed the correlation between PEDF and lung function.Results: First, we found that the expression of PEDF in cigarette smoke extract-treated cells increased 16.2-fold when compared with the control group. Next, we confirmed that 4 weeks’ exposure to cigarette smoke can upregulate PEDF levels in rat lung tissues. We also discovered that plasma PEDF in COPD patients was significantly increased when compared with either healthy nonsmoking or smoking subjects. Furthermore, circulating PEDF was correlated with inflammatory cytokine and blood neutrophil numbers, but it was reversely associated with a decline in forced expiratory volume in 1 second percent predicted.Conclusion: Our findings provide a novel link between PEDF and COPD. Elevated PEDF levels may be involved in promoting the development of COPD by performing proinflammatory functions. Keywords: chronic obstructive pulmonary disease, pigment epithelium-derived factor, cigarette smoke, inflammation

  18. Inflammasome-IL-1-Th17 response in allergic lung inflammation

    Institute of Scientific and Technical Information of China (English)

    Anne-Gaelle Besnard; Dieudonnée Togbe; Isabelle Couillin; Zoming Tan; Song Guo Zheng; Francois Erard; Marc Le Bert; Valérie Quesniaux; Bernhard Ryffel

    2012-01-01

    Allergic asthma has increased dramatically in prevalence and severity over the last three decades.Both clinical and experimental data support an important role of Th2 cell response in the allergic response.Recent investigations revealed that airway exposure to allergen in sensitized individuals causes the release of ATP and uric acid,activating the N LRP3 inflammasome complex and cleaving pro-IL-1β to mature IL-1β through caspase-1.The production of pro-IL-1β requires a toll-like receptor (TLR) 4 signal which is provided by the allergen.IL-1β creates a pro-inflammatory milieu with the production of IL-6 and chemokines which mobilize neutrophils and enhance Th17 cell differentiation in the lung.Here,we review our results showing that NLRP3 inflammasome activation is required to develop allergic airway inflammation in mice and that IL-17 and IL-22 production by Th17 cells plays a critical role in established asthma.Therefore,inflammasome activation leading to IL-1β production contributes to the control of allergic asthma by enhancing Th17 cell differentiation.

  19. Lung inflammation and genotoxicity following pulmonary exposure to nanoparticles in ApoE-/- mice

    DEFF Research Database (Denmark)

    Raun Jacobsen, Nicklas; Møller, Peter; Alstrup Jensen, Keld;

    2009-01-01

    Background: The toxic and inflammatory potential of 5 different types of nanoparticles were studied in a sensitive model for pulmonary effects in apolipoprotein E knockout mice (ApoE(-/-)). We studied the effects instillation or inhalation Printex 90 of carbon black ( CB) and compared CB instilla......Background: The toxic and inflammatory potential of 5 different types of nanoparticles were studied in a sensitive model for pulmonary effects in apolipoprotein E knockout mice (ApoE(-/-)). We studied the effects instillation or inhalation Printex 90 of carbon black ( CB) and compared CB...... and Mcp-1 mRNA were detected in lung tissue, 3 h and 24 h following instillation of SWCNT, CB and QDs. DNA damage in BAL cells, the fraction of neutrophils in BAL cells and protein in BAL fluid increased statistically significantly. Gold and C-60 particles caused much weaker inflammatory responses....... Conclusion: Our data suggest that ApoE(-/-) model is sensitive for evaluating particle induced inflammation. Overall QDs had greatest effects followed by CB and SWCNT with C-60 and gold being least inflammatory and DNA-damaging. However the gold was used at a much lower mass dose than the other particles...

  20. Effects of Respiratory Mycoplasma pneumoniae Infection on Allergen-Induced Bronchial Hyperresponsiveness and Lung Inflammation in Mice

    OpenAIRE

    Chu, Hong Wei; Honour, Joyce M.; Rawlinson, Catherine A.; Harbeck, Ronald J.; Richard J Martin

    2003-01-01

    Airway mycoplasma infection may be associated with asthma pathophysiology. However, the direct effects of mycoplasma infection on asthma remain unknown. Using a murine allergic-asthma model, we evaluated the effects of different timing of airway Mycoplasma pneumoniae infection on bronchial hyperresponsiveness (BHR), lung inflammation, and the protein levels of Th1 (gamma interferon [IFN-γ]) and Th2 (interleukin 4 [IL-4]) cytokines in bronchoalveolar lavage fluid. When mycoplasma infection occ...

  1. Exposure to low doses of formaldehyde during pregnancy suppresses the development of allergic lung inflammation in offspring

    International Nuclear Information System (INIS)

    Formaldehyde (FA) is an environmental and occupational pollutant, and its toxic effects on the immune system have been shown. Nevertheless, no data are available regarding the programming mechanisms after FA exposure and its repercussions for the immune systems of offspring. In this study, our objective was to investigate the effects of low-dose exposure of FA on pregnant rats and its repercussion for the development of allergic lung inflammation in offspring. Pregnant Wistar rats were assigned in 3 groups: P (rats exposed to FA (0.75 ppm, 1 h/day, 5 days/week, for 21 days)), C (rats exposed to vehicle of FA (distillated water)) and B (rats non-manipulated). After 30 days of age, the offspring was sensitised with ovalbumin (OVA)-alum and challenged with aerosolized OVA (1%, 15 min, 3 days). After 24 h the OVA challenge the parameters were evaluated. Our data showed that low-dose exposure to FA during pregnancy induced low birth weight and suppressed the development of allergic lung inflammation and tracheal hyperresponsiveness in offspring by mechanisms mediated by reduced anaphylactic antibodies synthesis, IL-6 and TNF-alpha secretion. Elevated levels of IL-10 were found. Any systemic alteration was detected in the exposed pregnant rats, although oxidative stress in the uterine environment was evident at the moment of the delivery based on elevated COX-1 expression and reduced cNOS and SOD-2 in the uterus. Therefore, we show the putative programming mechanisms induced by FA on the immune system for the first time and the mechanisms involved may be related to oxidative stress in the foetal microenvironment. - Highlights: • Formaldehyde exposure does not cause lung inflammation in pregnant rats. • Formaldehyde exposure suppresses allergic lung inflammation in the offspring. • Formaldehyde exposure induces oxidative stress in uterine environment

  2. Exposure to low doses of formaldehyde during pregnancy suppresses the development of allergic lung inflammation in offspring

    Energy Technology Data Exchange (ETDEWEB)

    Maiellaro, Marília [Department of Clinical and Toxicological Analyses, Faculty of Pharmaceutical Sciences, University of São Paulo, São Paulo (Brazil); Correa-Costa, Matheus [Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo (Brazil); Vitoretti, Luana Beatriz; Gimenes Júnior, João Antônio [Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, São Paulo (Brazil); Câmara, Niels Olsen Saraiva [Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo (Brazil); Tavares-de-Lima, Wothan [Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, São Paulo (Brazil); Farsky, Sandra Helena Poliselli [Department of Clinical and Toxicological Analyses, Faculty of Pharmaceutical Sciences, University of São Paulo, São Paulo (Brazil); Lino-dos-Santos-Franco, Adriana, E-mail: adrilino@usp.br [Department of Clinical and Toxicological Analyses, Faculty of Pharmaceutical Sciences, University of São Paulo, São Paulo (Brazil)

    2014-08-01

    Formaldehyde (FA) is an environmental and occupational pollutant, and its toxic effects on the immune system have been shown. Nevertheless, no data are available regarding the programming mechanisms after FA exposure and its repercussions for the immune systems of offspring. In this study, our objective was to investigate the effects of low-dose exposure of FA on pregnant rats and its repercussion for the development of allergic lung inflammation in offspring. Pregnant Wistar rats were assigned in 3 groups: P (rats exposed to FA (0.75 ppm, 1 h/day, 5 days/week, for 21 days)), C (rats exposed to vehicle of FA (distillated water)) and B (rats non-manipulated). After 30 days of age, the offspring was sensitised with ovalbumin (OVA)-alum and challenged with aerosolized OVA (1%, 15 min, 3 days). After 24 h the OVA challenge the parameters were evaluated. Our data showed that low-dose exposure to FA during pregnancy induced low birth weight and suppressed the development of allergic lung inflammation and tracheal hyperresponsiveness in offspring by mechanisms mediated by reduced anaphylactic antibodies synthesis, IL-6 and TNF-alpha secretion. Elevated levels of IL-10 were found. Any systemic alteration was detected in the exposed pregnant rats, although oxidative stress in the uterine environment was evident at the moment of the delivery based on elevated COX-1 expression and reduced cNOS and SOD-2 in the uterus. Therefore, we show the putative programming mechanisms induced by FA on the immune system for the first time and the mechanisms involved may be related to oxidative stress in the foetal microenvironment. - Highlights: • Formaldehyde exposure does not cause lung inflammation in pregnant rats. • Formaldehyde exposure suppresses allergic lung inflammation in the offspring. • Formaldehyde exposure induces oxidative stress in uterine environment.

  3. Violacein Treatment Modulates Acute and Chronic Inflammation through the Suppression of Cytokine Production and Induction of Regulatory T Cells.

    Science.gov (United States)

    Verinaud, Liana; Lopes, Stefanie Costa Pinto; Prado, Isabel Cristina Naranjo; Zanucoli, Fábio; Alves da Costa, Thiago; Di Gangi, Rosária; Issayama, Luidy Kazuo; Carvalho, Ana Carolina; Bonfanti, Amanda Pires; Niederauer, Guilherme Francio; Duran, Nelson; Costa, Fábio Trindade Maranhão; Oliveira, Alexandre Leite Rodrigues; Höfling, Maria Alice da Cruz; Machado, Dagmar Ruth Stach; Thomé, Rodolfo

    2015-01-01

    Inflammation is a necessary process to control infection. However, exacerbated inflammation, acute or chronic, promotes deleterious effects in the organism. Violacein (viola), a quorum sensing metabolite from the Gram-negative bacterium Chromobacterium violaceum, has been shown to protect mice from malaria and to have beneficial effects on tumors. However, it is not known whether this drug possesses anti-inflammatory activity. In this study, we investigated whether viola administration is able to reduce acute and chronic autoimmune inflammation. For that purpose, C57BL/6 mice were intraperitoneally injected with 1 μg of LPS and were treated with viola (3.5mg/kg) via i.p. at the same time-point. Three hours later, the levels of inflammatory cytokines in the sera and phenotypical characterization of leukocytes were determined. Mice treated with viola presented a significant reduction in the production of inflammatory cytokines compared with untreated mice. Interestingly, although viola is a compound derived from bacteria, it did not induce inflammation upon administration to naïve mice. To test whether viola would protect mice from an autoimmune inflammation, Experimental Autoimmune Encephalomyelitis (EAE)-inflicted mice were given viola i.p. at disease onset, at the 10th day from immunization. Viola-treated mice developed mild EAE disease in contrast with placebo-treated mice. The frequencies of dendritic cells and macrophages were unaltered in EAE mice treated with viola. However, the sole administration of viola augmented the levels of splenic regulatory T cells (CD4+Foxp3+). We also found that adoptive transfer of viola-elicited regulatory T cells significantly reduced EAE. Our study shows, for the first time, that violacein is able to modulate acute and chronic inflammation. Amelioration relied in suppression of cytokine production (in acute inflammation) and stimulation of regulatory T cells (in chronic inflammation). New studies must be conducted in order to

  4. Impact of cytokine expression in the pre-implanted donor lung on the development of chronic lung allograft dysfunction subtypes.

    Science.gov (United States)

    Saito, T; Takahashi, H; Kaneda, H; Binnie, M; Azad, S; Sato, M; Waddell, T K; Cypel, M; Liu, M; Keshavjee, S

    2013-12-01

    The long-term success of lung transplantation continues to be challenged by the development of chronic lung allograft dysfunction (CLAD). The purpose of this study was to investigate the relationship between cytokine expression levels in pre-implanted donor lungs and the posttransplant development of CLAD and its subtypes, bronchiolitis obliterans syndrome (BOS) and restrictive allograft syndrome (RAS). Of 109 patients who underwent bilateral lung or heart-lung transplantation and survived for more than 3 months, 50 BOS, 21 RAS and 38 patients with No CLAD were identified by pulmonary function test results. Using donor lung tissue biopsies sampled from each patient, expression levels of IL-6, IL-1β, IL-8, IL-10, interferon-γ and tumor necrosis factor-α mRNA were measured. IL-6 expression levels were significantly higher in pre-implanted lungs of patients that ultimately developed BOS compared to RAS and No CLAD (p = 0.025 and 0.011, respectively). Cox regression analysis demonstrated an association between high IL-6 expression levels and BOS development (hazard ratio = 4.98; 95% confidence interval = 2.42-10.2, p < 0.001). In conclusion, high IL-6 mRNA expression levels in pre-implanted donor lungs were associated with the development of BOS, not RAS. This association further supports the contention that early graft injury impacts on both late graft function and early graft function. PMID:24164971

  5. A STUDY OF ANTI - INFLAMMATORY ACTIVITY OF PLANT “TRIANTHEMA PORTULACASTRUM” IN CHRONIC MODELS OF INFLAMMATION

    Directory of Open Access Journals (Sweden)

    Suresh. S

    2015-06-01

    Full Text Available BACKGROUND: Trianthema portulacastrum is being used in Ayurveda since centuries for its medicinal values , hence this study was done to know if it has got anti - inflammatory activity in chronic models of inflammation, MATERIALS AND METHODS: Wistar albino rats were treated with whole plant ethanolic extract of trianthema portulacastrum 100mg \\ kg orally with 2% gum acacia , as suspending agent and indomethacin 20mg \\ kg as standard. And the effects were observed in chronic model of inflammation namely, rexin pellet induced granuloma model, RESULT: This study demon - strated that trianthema portulacastrum reduced significantly the dry weight of granuloma that was formed after rexin pellet implantation, CONCLUSION: Trianthema po rtulacastrum has got significant anti - inflammatory activity in chronic models of inflammation.

  6. Indoor air pollution from solid fuel use, chronic lung diseases and lung cancer in Harbin, Northeast China

    Energy Technology Data Exchange (ETDEWEB)

    Galeone, C.; Pelucchi, C.; La Vecchia, C.; Negri, E.; Bosetti, C.; Hu, J.F. [Ist. ric. farmacologiche Mario Negri, Milan (Italy)

    2008-10-15

    In some areas of China, indoor air pollution (IAP) originating principally from the combustion of solid fuels has a relevant role in lung cancer. Most previous studies focused on the female population and only a few on both the sexes. We analyzed the relationship between IAP from solid fuel use and selected chronic lung diseases and lung cancer risk in Harbin, Northeast China, an area with a very high base line risk of lung cancer for both the sexes. We used data from a case-control study conducted between 1987 and 1990, including 218 patients with incident, histologically confirmed lung cancer and 436 controls admitted to the same hospitals as cases. We calculated an index of IAP from solid fuel use exposure using data on heating type, cooking fuel used, and house measurements. Cases reported more frequently than controls on exposure to coal fuel for house heating and/or cooking, and the odds ratio (OR) for ever versus never exposed was 2.19 (95% confidence interval (CI): 1.08-4.46). The ORs of lung cancer according to subsequent tertiles of IAP exposure index were 1.82 (95% CI: 1.14-2.89) and 1.99 (95% CI: 1.26-3.15) as compared with the lowest tertile. The ORs of lung cancer for participants with a history of chronic bronchitis and tuberculosis were 3.79 (95% CI: 2.38-6.02) and 3.82 (95% CI: 1.97-7.41), respectively. This study gives further support and quantification of the positive association between IAP, history of selected nonmalignant lung diseases, and lung cancer risk for both the sexes.

  7. Role of Chitinase 3-Like-1 in Interleukin-18-Induced Pulmonary Type 1, Type 2, and Type 17 Inflammation; Alveolar Destruction; and Airway Fibrosis in the Murine Lung.

    Science.gov (United States)

    Kang, Min-Jong; Yoon, Chang Min; Nam, Milang; Kim, Do-Hyun; Choi, Je-Min; Lee, Chun Geun; Elias, Jack A

    2015-12-01

    Chitinase 3-like 1 (Chi3l1), which is also called YKL-40 in humans and BRP-39 in mice, is the prototypic chitinase-like protein. Recent studies have highlighted its impressive ability to regulate the nature of tissue inflammation and the magnitude of tissue injury and fibroproliferative repair. This can be appreciated in studies that highlight its induction after cigarette smoke exposure, during which it inhibits alveolar destruction and the genesis of pulmonary emphysema. IL-18 is also known to be induced and activated by cigarette smoke, and, in murine models, the IL-18 pathway has been shown to be necessary and sufficient to generate chronic obstructive pulmonary disease-like inflammation, fibrosis, and tissue destruction. However, the relationship between Chi3l1 and IL-18 has not been defined. To address this issue we characterized the expression of Chi3l1/BRP-39 in control and lung-targeted IL-18 transgenic mice. We also characterized the effects of transgenic IL-18 in mice with wild-type and null Chi3l1 loci. The former studies demonstrated that IL-18 is a potent stimulator of Chi3l1/BRP-39 and that this stimulation is mediated via IFN-γ-, IL-13-, and IL-17A-dependent mechanisms. The latter studies demonstrated that, in the absence of Chi3l1/BRP-39, IL-18 induced type 2 and type 17 inflammation and fibrotic airway remodeling were significantly ameliorated, whereas type 1 inflammation, emphysematous alveolar destruction, and the expression of cytotoxic T lymphocyte perforin, granzyme, and retinoic acid early transcript 1 expression were enhanced. These studies demonstrate that IL-18 is a potent stimulator of Chi3l1 and that Chi3l1 is an important mediator of IL-18-induced inflammatory, fibrotic, alveolar remodeling, and cytotoxic responses.

  8. Ethanol metabolism, oxidative stress, and endoplasmic reticulum stress responses in the lungs of hepatic alcohol dehydrogenase deficient deer mice after chronic ethanol feeding

    Energy Technology Data Exchange (ETDEWEB)

    Kaphalia, Lata [Department of Internal Medicine, The University of Texas Medical Branch, Galveston, TX 775555 (United States); Boroumand, Nahal [Department of Pathology, The University of Texas Medical Branch, Galveston, TX 775555 (United States); Hyunsu, Ju [Department of Preventive Medicine and Community Health, The University of Texas Medical Branch, Galveston, TX 775555 (United States); Kaphalia, Bhupendra S., E-mail: bkaphali@utmb.edu [Department of Pathology, The University of Texas Medical Branch, Galveston, TX 775555 (United States); Calhoun, William J. [Department of Internal Medicine, The University of Texas Medical Branch, Galveston, TX 775555 (United States)

    2014-06-01

    ethanol feeding causes oxidative stress, ER stress and inflammation in lungs of ADH– deer mice. • Chronic ethanol feeding generates FAEEs (nonoxidative metabolites of ethanol) in lungs of ADH– deer mice. • Chronic ethanol feeding induces CYP2E1 in the lungs of ADH– deer mice. • Lack of ER homeostasis due to a prolonged ethanol feeding could trigger inflammation.

  9. Transcriptomic analysis of pathways regulated by toll-like receptor 4 in a murine model of chronic pulmonary inflammation and carcinogenesis

    Directory of Open Access Journals (Sweden)

    Grissom Sherry F

    2009-11-01

    Full Text Available Abstract Background Therapeutic strategies exist for human pulmonary neoplasia, however due to the heterogeneity of the disease, most are not very effective. The innate immunity gene, toll-like receptor 4 (TLR4, protects against chronic pulmonary inflammation and tumorigenesis in mice, but the mechanism is unclear. This study was designed to identify TLR4-mediated gene expression pathways that may be used as prognostic indicators of susceptibility to lung tumorigenesis in mice and provide insight into the mechanism. Methods Whole lung mRNA was isolated from C.C3H-Tlr4Lps-d (BALBLps-d; Tlr4 mutant and BALB/c (Tlr4 normal mice following butylated hydroxytoluene (BHT-treatment (four weekly ip. injections; 150-200 mg/kg/each; "promotion". mRNA from micro-dissected tumors (adenomas and adjacent uninvolved tissue from both strains were also compared 27 wks after a single carcinogen injection (3-methylcholanthrene (MCA, 10 μg/g; "control" or followed by BHT (6 weekly ip. injections; 125-200 mg/kg/each; "progression". Bronchoalveolar lavage fluid was analyzed for inflammatory cell content and total protein determination, a marker of lung hyperpermeability; inflammation was also assessed using immunohistochemical staining for macrophages (F4/80 and lymphocytes (CD3 in mice bearing tumors (progression. Results During promotion, the majority of genes identified in the BALBLps-d compared to BALB/c mice (P Ereg, secreted phosphoprotein 1(Spp1, which can lead to cell growth and eventual tumor development. Inflammation was significantly higher in BALBLps-d compared to BALB/c mice during progression, similar to the observed response during tumor promotion in these strains. Increases in genes involved in signaling through the EGFR pathway (e.g. Ereg, Spp1 were also observed during progression in addition to continued inflammation, chemotactic, and immune response gene expression in the BALBLps-d versus BALB/c mice (P Conclusion This transcriptomic study

  10. LPS-induced lung inflammation in marmoset monkeys - an acute model for anti-inflammatory drug testing.

    Directory of Open Access Journals (Sweden)

    Sophie Seehase

    Full Text Available Increasing incidence and substantial morbidity and mortality of respiratory diseases requires the development of new human-specific anti-inflammatory and disease-modifying therapeutics. Therefore, new predictive animal models that closely reflect human lung pathology are needed. In the current study, a tiered acute lipopolysaccharide (LPS-induced inflammation model was established in marmoset monkeys (Callithrix jacchus to reflect crucial features of inflammatory lung diseases. Firstly, in an ex vivo approach marmoset and, for the purposes of comparison, human precision-cut lung slices (PCLS were stimulated with LPS in the presence or absence of the phosphodiesterase-4 (PDE4 inhibitor roflumilast. Pro-inflammatory cytokines including tumor necrosis factor-alpha (TNF-α and macrophage inflammatory protein-1 beta (MIP-1β were measured. The corticosteroid dexamethasone was used as treatment control. Secondly, in an in vivo approach marmosets were pre-treated with roflumilast or dexamethasone and unilaterally challenged with LPS. Ipsilateral bronchoalveolar lavage (BAL was conducted 18 hours after LPS challenge. BAL fluid was processed and analyzed for neutrophils, TNF-α, and MIP-1β. TNF-α release in marmoset PCLS correlated significantly with human PCLS. Roflumilast treatment significantly reduced TNF-α secretion ex vivo in both species, with comparable half maximal inhibitory concentration (IC(50. LPS instillation into marmoset lungs caused a profound inflammation as shown by neutrophilic influx and increased TNF-α and MIP-1β levels in BAL fluid. This inflammatory response was significantly suppressed by roflumilast and dexamethasone. The close similarity of marmoset and human lungs regarding LPS-induced inflammation and the significant anti-inflammatory effect of approved pharmaceuticals assess the suitability of marmoset monkeys to serve as a promising model for studying anti-inflammatory drugs.

  11. Fat-associated lymphoid clusters control local IgM secretion during pleural infection and lung inflammation

    Science.gov (United States)

    Jackson-Jones, Lucy H.; Duncan, Sheelagh M.; Magalhaes, Marlène S.; Campbell, Sharon M.; Maizels, Rick M.; McSorley, Henry J.; Allen, Judith E.; Bénézech, Cécile

    2016-01-01

    Fat-associated lymphoid clusters (FALC) are inducible structures that support rapid innate-like B-cell immune responses in the serous cavities. Little is known about the physiological cues that activate FALCs in the pleural cavity and more generally the mechanisms controlling B-cell activation in FALCs. Here we show, using separate models of pleural nematode infection with Litomosoides sigmodontis and Altenaria alternata induced acute lung inflammation, that inflammation of the pleural cavity rapidly activates mediastinal and pericardial FALCs. IL-33 produced by FALC stroma is crucial for pleural B1-cell activation and local IgM secretion. However, B1 cells are not the direct target of IL-33, which instead requires IL-5 for activation. Moreover, lung inflammation leads to increased IL-5 production by type 2 cytokine-producing innate lymphoid cells (ILC2) in the FALC. These findings reveal a link between inflammation, IL-33 release by FALC stromal cells, ILC2 activation and pleural B-cell activation in FALCs, resulting in local and antigen-specific IgM production. PMID:27582256

  12. Interleukin-33 Drives Activation of Alveolar Macrophages and Airway Inflammation in a Mouse Model of Acute Exacerbation of Chronic Asthma

    Directory of Open Access Journals (Sweden)

    Melissa M. Bunting

    2013-01-01

    Full Text Available We investigated the role of interleukin-33 (IL-33 in airway inflammation in an experimental model of an acute exacerbation of chronic asthma, which reproduces many of the features of the human disease. Systemically sensitized female BALB/c mice were challenged with a low mass concentration of aerosolized ovalbumin for 4 weeks to induce chronic asthmatic inflammation and then received a single moderate-level challenge to trigger acute airway inflammation simulating an asthmatic exacerbation. The inflammatory response and expression of cytokines and activation markers by alveolar macrophages (AM were assessed, as was the effect of pretreatment with a neutralizing antibody to IL-33. Compared to chronically challenged mice, AM from an acute exacerbation exhibited significantly enhanced expression of markers of alternative activation, together with enhanced expression of proinflammatory cytokines and of cell surface proteins associated with antigen presentation. In parallel, there was markedly increased expression of both mRNA and immunoreactivity for IL-33 in the airways. Neutralization of IL-33 significantly decreased both airway inflammation and the expression of proinflammatory cytokines by AM. Collectively, these data indicate that in this model of an acute exacerbation of chronic asthma, IL-33 drives activation of AM and has an important role in the pathogenesis of airway inflammation.

  13. Predomination of IL-17-producing tryptase-positive/chymase-positive mast cells in azoospermic chronic testicular inflammation.

    Science.gov (United States)

    Chen, S-J; Duan, Y-G; Haidl, G; Allam, J-P

    2016-08-01

    Chronic testicular inflammation and infection have been regarded as important factors in the pathogenesis of azoospermia. As key effector cells in innate and adaptive immune system, mast cells (MCs) were observed in inflammation and autoimmune disease. Furthermore, increased expression of tryptase-positive MCs has been reported in testicular disorders associated with male infertility/subfertility. However, little is known about the potential relationship between MCs and chronic testicular inflammation in azoospermic patients. Moreover, the preferential expression of MCs' subtypes in testis of these patients is still far from being understood. Thus, this study aimed to investigate characteristics of testicular MCs as well as their subtypes in azoospermic men with chronic testicular inflammation (AZI, n = 5) by immunohistochemical techniques. Our results showed significant increase of MCs in AZI, and more importantly, considerable numbers of tryptase-positive/chymase-positive MCs could also be demonstrated in AZI, when compared to control groups representing azoospermia without chronic testicular inflammation (AZW, n = 5) and normal spermatogenesis (NT, n = 5) respectively. Most interestingly, immunofluorescence staining revealed autoimmune-associated interleukin (IL)-17-producing MCs in AZI, whereas co-expression of MC markers with tumour necrosis factor (TNF)-α, IL-10 and IL-1β could not be detected. In conclusion, AZI is associated with significant increase of tryptase-positive/chymase-positive MCs expressing IL-17, and these MCs might contribute to the pathogenesis of AZI. PMID:26420243

  14. Biodiesel versus diesel exposure: Enhanced pulmonary inflammation, oxidative stress, and differential morphological changes in the mouse lung

    Energy Technology Data Exchange (ETDEWEB)

    Yanamala, Naveena, E-mail: wqu1@cdc.gov [Pathology and Physiology Research Branch/NIOSH/CDC, Morgantown, WV 26505 (United States); Hatfield, Meghan K., E-mail: wla4@cdc.gov [Pathology and Physiology Research Branch/NIOSH/CDC, Morgantown, WV 26505 (United States); Farcas, Mariana T., E-mail: woe7@cdc.gov [Pathology and Physiology Research Branch/NIOSH/CDC, Morgantown, WV 26505 (United States); Schwegler-Berry, Diane [Pathology and Physiology Research Branch/NIOSH/CDC, Morgantown, WV 26505 (United States); Hummer, Jon A., E-mail: qzh3@cdc.gov [Office of Mine Safety and Health Research/NIOSH/CDC, Pittsburgh, PA 15236 (United States); Shurin, Michael R., E-mail: shurinmr@upmc.edu [Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, PA (United States); Birch, M. Eileen, E-mail: mib2@cdc.gov [NIOSH/CDC, 4676 Columbia Parkway, Cincinnati, OH 45226 (United States); Gutkin, Dmitriy W., E-mail: dwgutkin@hotmail.com [Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, PA (United States); Kisin, Elena, E-mail: edk8@cdc.gov [Pathology and Physiology Research Branch/NIOSH/CDC, Morgantown, WV 26505 (United States); Kagan, Valerian E., E-mail: kagan@pitt.edu [Department of Environmental and Occupational Health, University of Pittsburgh, PA (United States); Bugarski, Aleksandar D., E-mail: zjl1@cdc.gov [Office of Mine Safety and Health Research/NIOSH/CDC, Pittsburgh, PA 15236 (United States); Shvedova, Anna A., E-mail: ats1@cdc.gov [Pathology and Physiology Research Branch/NIOSH/CDC, Morgantown, WV 26505 (United States); Department Physiology and Pharmacology, WVU, Morgantown, WV 26505 (United States)

    2013-10-15

    The use of biodiesel (BD) or its blends with petroleum diesel (D) is considered to be a viable approach to reduce occupational and environmental exposures to particulate matter (PM). Due to its lower particulate mass emissions compared to D, use of BD is thought to alleviate adverse health effects. Considering BD fuel is mainly composed of unsaturated fatty acids, we hypothesize that BD exhaust particles could induce pronounced adverse outcomes, due to their ability to readily oxidize. The main objective of this study was to compare the effects of particles generated by engine fueled with neat BD and neat petroleum-based D. Biomarkers of tissue damage and inflammation were significantly elevated in lungs of mice exposed to BD particulates. Additionally, BD particulates caused a significant accumulation of oxidatively modified proteins and an increase in 4-hydroxynonenal. The up-regulation of inflammatory cytokines/chemokines/growth factors was higher in lungs upon BD particulate exposure. Histological evaluation of lung sections indicated presence of lymphocytic infiltrate and impaired clearance with prolonged retention of BD particulate in pigment laden macrophages. Taken together, these results clearly indicate that BD exhaust particles could exert more toxic effects compared to D. - Highlights: • Exposure of mice to BDPM caused higher pulmonary toxicity compared to DPM. • Oxidative stress and inflammation were higher in BD vs to D exposed mice. • Inflammatory lymphocyte infiltrates were seen only in lungs of mice exposed to BD. • Ineffective clearance, prolonged PM retention was present only after BD exposure.

  15. Soy isoflavones avert chronic inflammation-induced bone loss and vascular disease

    Directory of Open Access Journals (Sweden)

    Lightfoot Stan A

    2007-09-01

    Full Text Available Abstract Background Evidence from epidemiological, clinical and animal studies suggests a link may exist between low bone density and cardiovascular disease, with inflammatory mediators implicated in the pathophysiology of both conditions. This project examined whether supplementation with soy isoflavones (IF, shown to have anti-inflammatory properties, could prevent tissue expression of TNF-α and the development of skeletal pathology in an animal model of chronic inflammation. Methods Eight-week old, intact, female C57BL/6J mice were used. In Phase 1, a lipopolysaccharide (LPS-dose response study (0, 0.133, 1.33 and 13.3 μg/d was conducted to determine the LPS dose to use in Phase 2. The results indicated the 1.33 μg LPS/d dose produced the greatest decrease in lymphocytes and increase in neutrophils. Subsequently, in Phase 2, mice were randomly assigned to one of six groups (n = 12–13 per group: 0 or 1.33 μg LPS/d (placebo or LPS in combination with 0, 126 or 504 mg aglycone equivalents of soy IF/kg diet (Control, Low or High dose IF. Mice were fed IF beginning 2 wks prior to the 30-d LPS study period. Results At the end of the study, no differences were detected in final body weights or uterine weights. In terms of trabecular bone microarchitecture, μCT analyses of the distal femur metaphysis indicated that LPS significantly decreased trabecular bone volume (BV/TV and number (TbN, and increased separation (TbSp. Trabecular bone strength (i.e. total force and stiffness were also compromised in response to LPS. The High IF dose provided protection against these detrimental effects on microarchitecture, but not biomechanical properties. No alterations in trabecular thickness (TbTh, or cortical bone parameters were observed in response to the LPS or IF. Immunohistomchemical staining showed that tumor necrosis factor (TNF-α was up-regulated by LPS in the endothelium of small myocardial arteries and arterioles as well as the tibial

  16. Role of reactive nitrogen species generated via inducible nitric oxide synthase in vesicant-induced lung injury, inflammation and altered lung functioning

    Energy Technology Data Exchange (ETDEWEB)

    Sunil, Vasanthi R., E-mail: sunilvr@eohsi.rutgers.edu [Department of Pharmacology and Toxicology, Rutgers University, Ernest Mario School of Pharmacy Piscataway, NJ (United States); Shen, Jianliang; Patel-Vayas, Kinal; Gow, Andrew J. [Department of Pharmacology and Toxicology, Rutgers University, Ernest Mario School of Pharmacy Piscataway, NJ (United States); Laskin, Jeffrey D. [Department of Environmental and Occupational Medicine, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, Piscataway, NJ (United States); Laskin, Debra L. [Department of Pharmacology and Toxicology, Rutgers University, Ernest Mario School of Pharmacy Piscataway, NJ (United States)

    2012-05-15

    Pulmonary toxicity induced by sulfur mustard and related vesicants is associated with oxidative stress. In the present studies we analyzed the role of reactive nitrogen species (RNS) generated via inducible nitric oxide synthase (iNOS) in lung injury and inflammation induced by vesicants using 2-chloroethyl ethyl sulfide (CEES) as a model. C57Bl/6 (WT) and iNOS −/− mice were sacrificed 3 days or 14 days following intratracheal administration of CEES (6 mg/kg) or control. CEES intoxication resulted in transient (3 days) increases in bronchoalveolar lavage (BAL) cell and protein content in WT, but not iNOS −/− mice. This correlated with expression of Ym1, a marker of oxidative stress in alveolar macrophages and epithelial cells. In contrast, in iNOS −/− mice, Ym1 was only observed 14 days post-exposure in enlarged alveolar macrophages, suggesting that they are alternatively activated. This is supported by findings that lung tumor necrosis factor and lipocalin Lcn2 expression, mediators involved in tissue repair were also upregulated at this time in iNOS −/− mice. Conversely, CEES-induced increases in the proinflammatory genes, monocyte chemotactic protein-1 and cyclooxygenase-2, were abrogated in iNOS −/− mice. In WT mice, CEES treatment also resulted in increases in total lung resistance and decreases in compliance in response to methacholine, effects blunted by loss of iNOS. These data demonstrate that RNS, generated via iNOS play a role in the pathogenic responses to CEES, augmenting oxidative stress and inflammation and suppressing tissue repair. Elucidating inflammatory mechanisms mediating vesicant-induced lung injury is key to the development of therapeutics to treat mustard poisoning. -- Highlights: ► Lung injury, inflammation and oxidative stress are induced by the model vesicant CEES ► RNS generated via iNOS are important in the CEES-induced pulmonary toxicity ► iNOS −/− mice are protected from CEES-induced lung toxicity and

  17. Role of reactive nitrogen species generated via inducible nitric oxide synthase in vesicant-induced lung injury, inflammation and altered lung functioning

    International Nuclear Information System (INIS)

    Pulmonary toxicity induced by sulfur mustard and related vesicants is associated with oxidative stress. In the present studies we analyzed the role of reactive nitrogen species (RNS) generated via inducible nitric oxide synthase (iNOS) in lung injury and inflammation induced by vesicants using 2-chloroethyl ethyl sulfide (CEES) as a model. C57Bl/6 (WT) and iNOS −/− mice were sacrificed 3 days or 14 days following intratracheal administration of CEES (6 mg/kg) or control. CEES intoxication resulted in transient (3 days) increases in bronchoalveolar lavage (BAL) cell and protein content in WT, but not iNOS −/− mice. This correlated with expression of Ym1, a marker of oxidative stress in alveolar macrophages and epithelial cells. In contrast, in iNOS −/− mice, Ym1 was only observed 14 days post-exposure in enlarged alveolar macrophages, suggesting that they are alternatively activated. This is supported by findings that lung tumor necrosis factor and lipocalin Lcn2 expression, mediators involved in tissue repair were also upregulated at this time in iNOS −/− mice. Conversely, CEES-induced increases in the proinflammatory genes, monocyte chemotactic protein-1 and cyclooxygenase-2, were abrogated in iNOS −/− mice. In WT mice, CEES treatment also resulted in increases in total lung resistance and decreases in compliance in response to methacholine, effects blunted by loss of iNOS. These data demonstrate that RNS, generated via iNOS play a role in the pathogenic responses to CEES, augmenting oxidative stress and inflammation and suppressing tissue repair. Elucidating inflammatory mechanisms mediating vesicant-induced lung injury is key to the development of therapeutics to treat mustard poisoning. -- Highlights: ► Lung injury, inflammation and oxidative stress are induced by the model vesicant CEES ► RNS generated via iNOS are important in the CEES-induced pulmonary toxicity ► iNOS −/− mice are protected from CEES-induced lung toxicity and

  18. Neuroimmune semaphorin 4D is necessary for optimal lung allergic inflammation.

    Science.gov (United States)

    Shanks, K; Nkyimbeng-Takwi, E H; Smith, E; Lipsky, M M; DeTolla, L J; Scott, D W; Keegan, A D; Chapoval, S P

    2013-12-01

    Neuroimmune semaphorin 4D (Sema4D) was found to be expressed and function in the nervous and immune systems. In the immune system, Sema4D is constitutively expressed on T cells and regulates T cell priming. In addition, it displays a stimulatory function on macrophages, DC, NK cells, and neutrophils. As all these cells are deeply involved in asthma pathology, we hypothesized that Sema4D plays a critical non-redundant regulatory role in allergic airway response. To test our hypothesis, we exposed Sema4D(-/-) and WT mice to OVA injections and challenges in the well-defined mouse model of OVA-induced experimental asthma. We observed a significant decrease in eosinophilic airway infiltration in allergen-treated Sema4D(-/-) mice relative to WT mice. This reduced allergic inflammatory response was associated with decreased BAL IL-5, IL-13, TGFβ1, IL-6, and IL-17A levels. In addition, T cell proliferation in OVA₃₂₃₋₃₃₉-restimulated Sema4D(-/-) cell cultures was downregulated. We also found increased Treg numbers in spleens of Sema4D(-/-) mice. However, airway hyperreactivity (AHR) to methacholine challenges was not affected by Sema4D deficiency in either acute or chronic experimental disease setting. Surprisingly, lung DC number and activation were not affected by Sema4D deficiency. These data provide a new insight into Sema4D biology and define Sema4D as an important regulator of Th2-driven lung pathophysiology and as a potential target for a combinatory disease immunotherapy. PMID:23911404

  19. Neutralization of interleukin-17A delays progression of silica-induced lung inflammation and fibrosis in C57BL/6 mice

    International Nuclear Information System (INIS)

    Silica exposure can cause lung inflammation and fibrosis, known as silicosis. Interleukin-17A (IL-17A) and Th17 cells play a pivotal role in controlling inflammatory diseases. However, the roles of IL-17A and Th17 cells in the progress of silica-induced inflammation and fibrosis are poorly understood. This study explored the effects of IL-17A on silica-induced inflammation and fibrosis. We used an anti-mouse IL-17A antibody to establish an IL-17A-neutralized mice model, and mice were exposed to silica to establish an experimental silicosis model. We showed that IL-17A neutralization delayed neutrophil accumulation and progression of silica-induced lung inflammation and fibrosis. IL-17A neutralization reduced the percentage of Th17 in CD4 + T cells, decreased IL-6 and IL-1β expression, and increased Tregs at an early phase of silica-induced inflammation. Neutralization of IL-17A delayed silica-induced Th1/Th2 immune and autoimmune responses. These results suggest that IL-17A neutralization alleviates early stage silica-induced lung inflammation and delays progression of silica-induced lung inflammation and fibrosis. Neutralization of IL-17A suppressed Th17 cell development by decreasing IL-6 and/or IL-1β and increased Tregs at an early phase of silica-induced inflammation. Neutralization of IL-17A also delayed the Th1/Th2 immune response during silica-induced lung inflammation and fibrosis. IL-17A may play a pivotal role in the early phase of silica-induced inflammation and may mediate the Th immune response to influence silica-induced lung inflammation and fibrosis in mice. - Highlights: • Neutralization of IL-17A alleviated silica-induced lung inflammation of early stage. • Neutralization of IL-17A decreased Th17 cells and increased Tregs. • IL-17A mediated the reciprocal relationship of Th17/Tregs by IL-6 and/or IL-1β. • Neutralization of IL-17A delayed silica-induced Th1/Th2 immune response. • Neutralization of IL-17A delayed silica-induced lung

  20. Neutralization of interleukin-17A delays progression of silica-induced lung inflammation and fibrosis in C57BL/6 mice

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Ying; Li, Cuiying [Division of Pneumoconiosis, School of Public Health, China Medical University, Shenyang, Liaoning (China); Weng, Dong [Division of Pneumoconiosis, School of Public Health, China Medical University, Shenyang, Liaoning (China); Clinical Translational Research Center, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai (China); Song, Laiyu; Tang, Wen; Dai, Wujing; Yu, Ye; Liu, Fangwei; Zhao, Ming; Lu, Chunwei [Division of Pneumoconiosis, School of Public Health, China Medical University, Shenyang, Liaoning (China); Chen, Jie, E-mail: chenjie@mail.cmu.edu.cn [Division of Pneumoconiosis, School of Public Health, China Medical University, Shenyang, Liaoning (China)

    2014-02-15

    Silica exposure can cause lung inflammation and fibrosis, known as silicosis. Interleukin-17A (IL-17A) and Th17 cells play a pivotal role in controlling inflammatory diseases. However, the roles of IL-17A and Th17 cells in the progress of silica-induced inflammation and fibrosis are poorly understood. This study explored the effects of IL-17A on silica-induced inflammation and fibrosis. We used an anti-mouse IL-17A antibody to establish an IL-17A-neutralized mice model, and mice were exposed to silica to establish an experimental silicosis model. We showed that IL-17A neutralization delayed neutrophil accumulation and progression of silica-induced lung inflammation and fibrosis. IL-17A neutralization reduced the percentage of Th17 in CD4 + T cells, decreased IL-6 and IL-1β expression, and increased Tregs at an early phase of silica-induced inflammation. Neutralization of IL-17A delayed silica-induced Th1/Th2 immune and autoimmune responses. These results suggest that IL-17A neutralization alleviates early stage silica-induced lung inflammation and delays progression of silica-induced lung inflammation and fibrosis. Neutralization of IL-17A suppressed Th17 cell development by decreasing IL-6 and/or IL-1β and increased Tregs at an early phase of silica-induced inflammation. Neutralization of IL-17A also delayed the Th1/Th2 immune response during silica-induced lung inflammation and fibrosis. IL-17A may play a pivotal role in the early phase of silica-induced inflammation and may mediate the Th immune response to influence silica-induced lung inflammation and fibrosis in mice. - Highlights: • Neutralization of IL-17A alleviated silica-induced lung inflammation of early stage. • Neutralization of IL-17A decreased Th17 cells and increased Tregs. • IL-17A mediated the reciprocal relationship of Th17/Tregs by IL-6 and/or IL-1β. • Neutralization of IL-17A delayed silica-induced Th1/Th2 immune response. • Neutralization of IL-17A delayed silica-induced lung

  1. Correlation of measurable serum markers of inflammation with lung levels following bilateral femur fracture in a rat model

    Directory of Open Access Journals (Sweden)

    Benjamin W Sears

    2010-08-01

    Full Text Available Benjamin W Sears1, Dustin Volkmer1, Sherri Yong2, Ryan D Himes1, Kristen Lauing1, Michele Morgan1, Michael D Stover1, John J Callaci11Department of Orthopaedics, 2Department of Pathology, Loyola University Medical Center, Maywood, IL, USAIntroduction: Evaluation of the systemic inflammatory status following major orthopedic trauma has become an important adjunct in basing post-injury clinical decisions. In the present study, we examined the correlation of serum and lung inflammatory marker levels following bilateral femur fracture.Materials and methods: 45 Sprague Dawley rats underwent sham operation or bilateral femoral intramedullary pinning and mid-diaphyseal closed fracture via blunt guillotine. Animals were euthanized at specific time points after injury. Serum and lung tissue were collected, and 24 inflammatory markers were analyzed by immunoassay. Lung histology was evaluated by a blinded pathologist.Results: Bilateral femur fracture significantly increased serum markers of inflammation including interleukin (IL-2, IL-6, IL-10, GM-CSF, KC/GRO, MCP-1, and WBC. Femur fracture ­significantly increased serum and lung levels of IL-1a and KC/GRO at 6 hours. Lung levels of IL-6 ­demonstrated a trend towards significance. Histologic changes in pulmonary tissue after fracture included pulmonary edema and bone elements including cellular hematopoietic cells, bone fragments and marrow emboli.Discussion and conclusion: Our results indicate that bilateral femur fracture with fixation in rats results in increases in serum markers of inflammation. Among the inflammatory markers measured, rise in the serum KC/GRO (CINC-1, a homolog to human IL-8, correlated with elevated levels of lung KC/GRO. Ultimately, analysis of serum levels of KC/GRO (CINC-1, or human IL-8, may be a useful adjunct to guide clinical decisions regarding surgical timing.Keywords: blunt trauma, injury, cytokine, IL-8, bone marrow emboli

  2. Influenza virus-induced lung inflammation was modulated by cigarette smoke exposure in mice.

    Directory of Open Access Journals (Sweden)

    Yan Han

    Full Text Available Although smokers have increased susceptibility and severity of seasonal influenza virus infection, there is no report about the risk of 2009 pandemic H1N1 (pdmH1N1 or avian H9N2 (H9N2/G1 virus infection in smokers. In our study, we used mouse model to investigate the effect of cigarette smoke on pdmH1N1 or H9N2 virus infection. Mice were exposed to cigarette smoke for 21 days and then infected with pdmH1N1 or H9N2 virus. Control mice were exposed to air in parallel. We found that cigarette smoke exposure alone significantly upregulated the lung inflammation. Such prior cigarette smoke exposure significantly reduced the disease severity of subsequent pdmH1N1 or H9N2 virus infection. For pdmH1N1 infection, cigarette smoke exposed mice had significantly lower mortality than the control mice, possibly due to the significantly decreased production of inflammatory cytokines and chemokines. Similarly, after H9N2 infection, cigarette smoke exposed mice displayed significantly less weight loss, which might be attributed to lower cytokines and chemokines production, less macrophages, neutrophils, CD4+ and CD8+ T cells infiltration and reduced lung damage compared to the control mice. To further investigate the underlying mechanism, we used nicotine to mimic the effect of cigarette smoke both in vitro and in vivo. Pre-treating the primary human macrophages with nicotine for 72 h significantly decreased their expression of cytokines and chemokines after pdmH1N1 or H9N2 infection. The mice subcutaneously and continuously treated with nicotine displayed significantly less weight loss and lower inflammatory response than the control mice upon pdmH1N1 or H9N2 infection. Moreover, α7 nicotinic acetylcholine receptor knockout mice had more body weight loss than wild-type mice after cigarette smoke exposure and H9N2 infection. Our study provided the first evidence that the pathogenicity of both pdmH1N1 and H9N2 viruses was alleviated in cigarette smoke exposed

  3. Characterising novel anti-biofilm targets for the treatment of chronic Pseudomonas aeruginosa infection in the cystic fibrosis lung

    OpenAIRE

    McCarthy, Ronan

    2014-01-01

    The global rise in antibiotic resistance is a significant problem facing healthcare professionals. In particular within the cystic fibrosis (CF) lung, bacteria can establish chronic infection and resistance to a wide array of antibiotic therapies. One of the principle pathogens associated with chronic infection in the CF lung is Pseudomonas aeruginosa. P. aeruginosa can establish chronic infection in the CF lung partly through the use of the biofilm mode of growth. This biofilm mode of growth...

  4. Does gamma-aminobutyric acid (GABA influence the development of chronic inflammation in rheumatoid arthritis?

    Directory of Open Access Journals (Sweden)

    Bridges S Louis

    2008-01-01

    Full Text Available Abstract Background Recent studies have demonstrated a role for spinal p38 MAP kinase (MAPK in the development of chronic inflammation and peripheral arthritis and a role for GABA in the inhibition of p38 MAPK mediated effects. Integrating these data suggests that GABA may play a role in downregulating mechanisms that lead to the production of proinflammatory agents such as interleukin-1, interleukin-6, and matrix metalloproteinase 3 – agents implicated in the pathogenesis of rheumatoid arthritis (RA. Genetic studies have also associated RA with members of the p38 MAPK pathway. Hypothesis We propose a hypothesis for an inefficient GABA signaling system that results in unchecked proinflammatory cytokine production via the p38 MAPK pathway. This model also supports the need for increasing research in the integration of immunology and neuroscience.

  5. [Understanding and treatment strategy of the pathogenesis of periodontal disease based on chronic inflammation].

    Science.gov (United States)

    Murakami, Tomohiko

    2016-05-01

    Prolonged inflammation continuously promotes the infiltration of macrophages in the organization and chronically induces the production of pro-inflammatory cytokines such as TNF and IL-1. In periodontal tissues, these inflammatory cytokines enhance the differentiation and activity of osteoclasts, which cause destruction of the alveolar bone. Therefore, inhibition of inflammatory cytokine production leads to the prevention or treatment of periodontal disease. IL-1 is a pro-inflammatory cytokine that strongly enhances the bone-resorbing activity of osteoclasts. Elucidation of mechanisms for the production of IL-1 is critical for understanding the pathogenesis of periodontal disease. This paper reviews recent findings of the molecular mechanisms regulating IL-1 production and focuses on inflammasome.

  6. Treatment of 15 Cases of Chronic Pelvic Inflammation by Acupuncture plus Herbal Enema

    Institute of Scientific and Technical Information of China (English)

    SHEN Jian

    2005-01-01

    Fifteen cases of chronic pelvic inflammation were treated by needling Guanyuan (CV 4), Qihai (CV 6), Sanyinjiao (SP 6), Zhongji (CV 3), Shidao (ST 28), Diji (SP 8), Zusanli (ST 36), Shenshu (BL 23), Dachangshu (BL 25) and Ciliao(BL 32) in combination with herbal enema effective to clear heat and relieve toxin, activate blood and resolve stagnant blood.After 2-course treatment, 13 cases were cured and 2 cases were improved.%针刺关元,气海,三阴交,中极,水道,地机,足三里,肾俞,大肠俞和次髎穴,同时用清热解毒和活血化瘀中药进行保留灌肠,治疗了15例慢性盆腔炎患者,经过2个疗程治疗,13例痊愈,2例有效.

  7. Chronic urticaria in patients with autoimmune thyroiditis: Significance of severity of thyroid gland inflammation

    Directory of Open Access Journals (Sweden)

    Mustafa Gulec

    2011-01-01

    Full Text Available Background: There is a clear association between autoimmune thyroiditis (AT and chronic urticaria/angioedema (CUA. However, not all patients with AT demonstrate urticaria. Aims: The aim of the study was to investigate in which patients with AT did CUA become a problem. A sensitive inflammation marker, neopterine (NP was used to confirm whether the severity of inflammation in the thyroid gland was responsible for urticaria or not. Methods: Neopterine levels were assessed in patients with AT with urticaria and without urticaria. Furthermore, levels were compared in relation to pre and post levothyroxine treatment. Twenty-seven patients with urticaria (Group 1 and 28 patients without urticaria (Group 2 were enrolled in the study. A course of levothyroxine treatment was given to all patients, and urine neopterine levels before and after the trial were obtained. Results: All patients completed the trial. Mean age in Group 1 and Group 2 was similar (35.70 ± 10.86 years and 38.36 ± 10.38 years, respectively (P=0.358. Pre-treatment urine neopterine levels were significantly higher in Group 1 (P=0.012. Post-treatment levels decreased in each group, as expected. However, the decrease in the neopterine level was insignificant in the patients of Group 2 (P=0.282. In Group 1, a significant decrease in post-treatment neopterine levels (P=0.015 was associated with the remission of urticaria. Conclusion: In patients with CUA and AT, pre-treatment elevated levels of NP, and its decrease with levothyroxine treatment along with symptomatic relief in urticaria, may be evidence of the relationship between the degree of inflammation in thyroid and presence of urticaria.

  8. Cartography of Pathway Signal Perturbations Identifies Distinct Molecular Pathomechanisms in Malignant and Chronic Lung Diseases.

    Science.gov (United States)

    Arakelyan, Arsen; Nersisyan, Lilit; Petrek, Martin; Löffler-Wirth, Henry; Binder, Hans

    2016-01-01

    Lung diseases are described by a wide variety of developmental mechanisms and clinical manifestations. Accurate classification and diagnosis of lung diseases are the bases for development of effective treatments. While extensive studies are conducted toward characterization of various lung diseases at molecular level, no systematic approach has been developed so far. Here we have applied a methodology for pathway-centered mining of high throughput gene expression data to describe a wide range of lung diseases in the light of shared and specific pathway activity profiles. We have applied an algorithm combining a Pathway Signal Flow (PSF) algorithm for estimation of pathway activity deregulation states in lung diseases and malignancies, and a Self Organizing Maps algorithm for classification and clustering of the pathway activity profiles. The analysis results allowed clearly distinguish between cancer and non-cancer lung diseases. Lung cancers were characterized by pathways implicated in cell proliferation, metabolism, while non-malignant lung diseases were characterized by deregulations in pathways involved in immune/inflammatory response and fibrotic tissue remodeling. In contrast to lung malignancies, chronic lung diseases had relatively heterogeneous pathway deregulation profiles. We identified three groups of interstitial lung diseases and showed that the development of characteristic pathological processes, such as fibrosis, can be initiated by deregulations in different signaling pathways. In conclusion, this paper describes the pathobiology of lung diseases from systems viewpoint using pathway centered high-dimensional data mining approach. Our results contribute largely to current understanding of pathological events in lung cancers and non-malignant lung diseases. Moreover, this paper provides new insight into molecular mechanisms of a number of interstitial lung diseases that have been studied to a lesser extent.

  9. Chronic psychosocial stress increases the risk for inflammation-related colon carcinogenesis in male mice.

    Science.gov (United States)

    Peters, Sebastian; Grunwald, Nicole; Rümmele, Petra; Endlicher, Esther; Lechner, Anja; Neumann, Inga D; Obermeier, Florian; Reber, Stefan O

    2012-07-01

    Patients with inflammatory bowel diseases (IBDs) have a higher risk of developing colorectal cancer (CRC) than the general population. Furthermore, chronic psychosocial stress increases the likelihood of developing IBD and multiple types of malignant neoplasms, including CRC. Here, for the first time, we investigate the effects of chronic psychosocial stress in male mice on an artificially induced CRC, by employing the chronic subordinate colony (CSC) housing paradigm in combination with the reliable azoxymethane (AOM)/dextran sodium sulfate (DSS) CRC model. Colonoscopy revealed that CSC mice showed accelerated macroscopic suspect lesions. In addition, more CSC mice developed low-grade dysplasia (LGD) and/or high-grade dysplasia (HGD) in the colonic tissue compared to the single-housed control mice (SHC). CSC mice showed an increased number of Ki67+ and a decreased number of terminal deoxynucleotidyl transferase dUTP nick end labeling epithelial cells in colonic tissue. Colonic liver receptor homolog-1 (LRH-1), cyclooxygenase II (COXII), tumor necrosis factor, forkhead box P3 (FoxP3) mRNA as well as colonic ß-catenin, COXII, and LRH-1 protein expression were also increased in CSC compared with SHC mice. Although the number of CD4+ Th cells was increased, a tendency toward a decreased colonic interferon-γ (IFN-γ) mRNA expression was observed. Furthermore, despite an increased percentage of CD3+ cells and CD3+/FoxP3+ double-positive cells within mesenteric lymph node cells of CSC mice, IFN-γ secretion from these cells was unaffected. Altogether, our results suggest that chronic psychosocial stress increases the risk for AOM/DSS-induced and, thus, inflammation-related CRC. Finally, assessment of additional time points may test whether the shift from tumor-protective Th1 cell to regulatory T-cell immunity represents a consequence of increased carcinogenesis or a causal factor involved in its development.

  10. Characterisation of cochlear inflammation in mice following acute and chronic noise exposure.

    Science.gov (United States)

    Tan, Winston J T; Thorne, Peter R; Vlajkovic, Srdjan M

    2016-08-01

    Oxidative stress has been established as the key mechanism of the cochlear damage underlying noise-induced hearing loss, however, emerging evidence suggests that cochlear inflammation may also be a major contributor. This study aimed to improve our understanding of the cochlear inflammatory response associated with acute and chronic noise exposure. C57BL/6 mice were exposed to acute traumatic noise (100 dBSPL, 8-16 kHz for 24 h) and their cochleae collected at various intervals thereafter, up to 7 days. Using quantitative RT-PCR and immunohistochemistry, changes in expression levels of proinflammatory cytokines (TNF-α, IL-1β), chemokines (CCL2) and cell adhesion molecules (ICAM-1) were studied. All gene transcripts displayed similar dynamics of expression, with an early upregulation at 6 h post-exposure, followed by a second peak at 7 days. ICAM-1 immunoexpression increased significantly in the inferior region of the spiral ligament, peaking 24 h post-exposure. The early expression of proinflammatory mediators likely mediates the recruitment and extravasation of inflammatory cells into the noise-exposed cochlea. The occurrence of the latter expression peak is not clear, but it may be associated with reparative processes initiated in response to cochlear damage. Chronic exposure to moderate noise (90 dBSPL, 8-16 kHz, 2 h/day, up to 4 weeks) also elicited an inflammatory response, reaching a maximum after 2 weeks, suggesting that cochlear damage and hearing loss associated with chronic environmental noise exposure may be linked to inflammatory processes in the cochlea. This study thus provides further insight into the dynamics of the cochlear inflammatory response induced by exposure to acute and chronic noise. PMID:27109494

  11. Elevated [11C]-D-deprenyl uptake in chronic Whiplash Associated Disorder suggests persistent musculoskeletal inflammation.

    Directory of Open Access Journals (Sweden)

    Clas Linnman

    Full Text Available There are few diagnostic tools for chronic musculoskeletal pain as structural imaging methods seldom reveal pathological alterations. This is especially true for Whiplash Associated Disorder, for which physical signs of persistent injuries to the neck have yet to be established. Here, we sought to visualize inflammatory processes in the neck region by means Positron Emission Tomography using the tracer (11C-D-deprenyl, a potential marker for inflammation. Twenty-two patients with enduring pain after a rear impact car accident (Whiplash Associated Disorder grade II and 14 healthy controls were investigated. Patients displayed significantly elevated tracer uptake in the neck, particularly in regions around the spineous process of the second cervical vertebra. This suggests that whiplash patients have signs of local persistent peripheral tissue inflammation, which may potentially serve as a diagnostic biomarker. The present investigation demonstrates that painful processes in the periphery can be objectively visualized and quantified with PET and that (11C-D-deprenyl is a promising tracer for these purposes.

  12. Chronic Multifocal Inflammation of the Alveolar Bone Mimicking Malignancy: A Case Report

    Directory of Open Access Journals (Sweden)

    Shahidi Sh.

    2012-03-01

    Full Text Available ronic inflammation of the alveolar bone is a great clinical and radiologic mimic, which merits recognition by the clinician and pathologist. The patient can thus be reassured of the proper early treatment and a favorable prognosis. Occasionally, it is difficult to differentiate inflammatory lesions from malign-ant tumors. The aim of this report is to present a case with an inflammatory lesion mimicking malignant condition.We report a 19-year-old male complaining of rapid onset gingival swelling of the right side of both jaws and looseness of the right upper molar teeth in 20 days. Based on the acute onset of the gingival hyperplasia, severe looseness of the affected teeth especially in the maxilla, and the patient's age, multifocal rapid growing malignant condition was not ruled out. The lesion was misdiagnosed as a malignant condition by clinical and radiographic examination. The whole body bone scan showed no significant increased uptake in the right oral cavity compatible with no active bony pathology. The surgical pathology findings of the lesion showed severe chronic inflammation with surface epithelial hyperplasia.The initial diagnosis of the lesion was malignant condition but it was ruled out by bone scan and histological appearance.

  13. Chronic Inflammation and Neutrophil Activation as Possible Causes of Joint Diseases in Ballet Dancers

    Directory of Open Access Journals (Sweden)

    Leandro da Silva Borges

    2014-01-01

    Full Text Available Herein, we investigated the effects of a ballet class on the kinetic profiles of creatine kinase (CK and lactate dehydrogenase (LDH activities, cytokines, complement component 3 (C3, and the concentrations of immunoglobulin (Ig, IgA and IgM, in ballerinas. We also verified neutrophil death and ROS release. Blood samples were taken from 13 dancers before, immediately after, and 18 hours after a ballet class. The ballet class increased the plasma activities of CK-total (2.0-fold immediately after class, while the activities of CK-cardiac muscle (1.0-fold and LDH (3.0-fold were observed to increase 18 hours after the class. Levels of the TNF-α, IL-1β, IgG, and IgA were not affected under the study conditions. The exercise was found to induce neutrophil apoptosis (6.0-fold 18 hours after the ballet class. Additionally, immediately after the ballet class, the neutrophils from the ballerinas were found to be less responsive to PMA stimulus. Conclusion. Ballet class was found to result in inflammation in dancers. The inflammation caused by the ballet class remained for 18 hours after the exercise. These findings are important in preventing the development of chronic lesions that are commonly observed in dancers, such as those with arthritis and synovitis.

  14. A gut microbiota-targeted dietary intervention for amelioration of chronic inflammation underlying metabolic syndrome.

    Science.gov (United States)

    Xiao, Shuiming; Fei, Na; Pang, Xiaoyan; Shen, Jian; Wang, Linghua; Zhang, Baorang; Zhang, Menghui; Zhang, Xiaojun; Zhang, Chenhong; Li, Min; Sun, Lifeng; Xue, Zhengsheng; Wang, Jingjing; Feng, Jie; Yan, Feiyan; Zhao, Naisi; Liu, Jiaqi; Long, Wenmin; Zhao, Liping

    2014-02-01

    Chronic inflammation induced by endotoxin from a dysbiotic gut microbiota contributes to the development of obesity-related metabolic disorders. Modification of gut microbiota by a diet to balance its composition becomes a promising strategy to help manage obesity. A dietary scheme based on whole grains, traditional Chinese medicinal foods, and prebiotics (WTP diet) was designed to meet human nutritional needs as well as balance the gut microbiota. Ninety-three of 123 central obese volunteers (BMI ≥ 28 kg m(-2) ) completed a self-controlled clinical trial consisting of 9-week intervention on WTP diet followed by a 14-week maintenance period. The average weight loss reached 5.79 ± 4.64 kg (6.62 ± 4.94%), in addition to improvement in insulin sensitivity, lipid profiles, and blood pressure. Pyrosequencing of fecal samples showed that phylotypes related to endotoxin-producing opportunistic pathogens of Enterobacteriaceae and Desulfovibrionaceae were reduced significantly, while those related to gut barrier-protecting bacteria of Bifidobacteriaceae increased. Gut permeability, measured as lactulose/mannitol ratio, was decreased compared with the baseline. Plasma endotoxin load as lipopolysaccharide-binding protein was also significantly reduced, with concomitant decrease in tumor necrosis factor-α, interleukin-6, and an increase in adiponectin. These results suggest that modulation of the gut microbiota via dietary intervention may enhance the intestinal barrier integrity, reduce circulating antigen load, and ultimately ameliorate the inflammation and metabolic phenotypes.

  15. Elevated [11C]-D-deprenyl uptake in chronic Whiplash Associated Disorder suggests persistent musculoskeletal inflammation.

    Science.gov (United States)

    Linnman, Clas; Appel, Lieuwe; Fredrikson, Mats; Gordh, Torsten; Söderlund, Anne; Långström, Bengt; Engler, Henry

    2011-01-01

    There are few diagnostic tools for chronic musculoskeletal pain as structural imaging methods seldom reveal pathological alterations. This is especially true for Whiplash Associated Disorder, for which physical signs of persistent injuries to the neck have yet to be established. Here, we sought to visualize inflammatory processes in the neck region by means Positron Emission Tomography using the tracer (11)C-D-deprenyl, a potential marker for inflammation. Twenty-two patients with enduring pain after a rear impact car accident (Whiplash Associated Disorder grade II) and 14 healthy controls were investigated. Patients displayed significantly elevated tracer uptake in the neck, particularly in regions around the spineous process of the second cervical vertebra. This suggests that whiplash patients have signs of local persistent peripheral tissue inflammation, which may potentially serve as a diagnostic biomarker. The present investigation demonstrates that painful processes in the periphery can be objectively visualized and quantified with PET and that (11)C-D-deprenyl is a promising tracer for these purposes. PMID:21541010

  16. Diet and Inflammation: Possible Effects on Immunity, Chronic Diseases, and Life Span.

    Science.gov (United States)

    Ricordi, Camillo; Garcia-Contreras, Marta; Farnetti, Sara

    2015-01-01

    Chronic inflammation negatively impacts all physiological functions, causing an array of degenerative conditions including diabetes; cancer; cardiovascular, osteo-articular, and neurodegenerative diseases; autoimmunity disorders; and aging. In particular, there is a growing knowledge of the role that gene transcription factors play in the inflammatory process. Obesity, metabolic syndrome, and diabetes represent multifactorial conditions resulting from improper balances of hormones and gene expression. In addition, these conditions have a strong inflammatory component that can potentially be impacted by the diet. It can reduce pro-inflammatory eicosanoids that can alter hormonal signaling cascades to the modulation of the innate immune system and gene transcription factors. Working knowledge of the impact of how nutrients, especially dietary fatty acids and polyphenols, can impact these various molecular targets makes it possible to develop a general outline of an anti-inflammatory diet that offers a unique, nonpharmacological approach in treating obesity, metabolic syndrome, and diabetes. Several important bioactive dietary components can exert their effect through selected inflammatory pathways that can affect metabolic and genetic changes. In fact, dietary components that can modulate glucose and insulin levels, as well as any other mediator that can activate nuclear factor-kB, can also trigger inflammation through common pathway master switches. PMID:26400428

  17. A Potential Role for Acrolein in Neutrophil-Mediated Chronic Inflammation.

    Science.gov (United States)

    Noerager, Brett D; Xu, Xin; Davis, Virginia A; Jones, Caleb W; Okafor, Svetlana; Whitehead, Alicia; Blalock, J Edwin; Jackson, Patricia L

    2015-12-01

    Neutrophils (PMNs) are key mediators of inflammatory processes throughout the body. In this study, we investigated the role of acrolein, a highly reactive aldehyde that is ubiquitously present in the environment and produced endogenously at sites of inflammation, in mediating PMN-mediated degradation of collagen facilitating proline-glycine-proline (PGP) production. We treated peripheral blood neutrophils with acrolein and analyzed cell supernatants and lysates for matrix metalloproteinase-9 (MMP-9) and prolyl endopeptidase (PE), assessed their ability to break down collagen and release PGP, and assayed for the presence of leukotriene A4 hydrolase (LTA4H) and its ability to degrade PGP. Acrolein treatment induced elevated production and functionality of collagen-degrading enzymes and generation of PGP fragments. Meanwhile, LTA4H levels and triaminopeptidase activity declined with increasing concentrations of acrolein thereby sparing PGP from enzymatic destruction. These findings suggest that acrolein exacerbates the acute inflammatory response mediated by neutrophils and sets the stage for chronic pulmonary and systemic inflammation.

  18. Chronic Pelvic Inflammation Diminished Ovarian Reserve as Indicated by Serum Anti Mulerrian Hormone.

    Directory of Open Access Journals (Sweden)

    Linlin Cui

    Full Text Available To explore the potential damaging effect of chronic pelvic inflammation on ovarian reserve.Case-control study.A total of 122 women with bilateral tubal occlusion, diagnosed by hysterosalipingography (HSG and 217 women with normal fallopians were recruited.Serum anti-Mullerian hormone (AMH, basic follicle-stimulating hormone (FSH, luteining hormone (LH, estradiol (E2, and testosterone (T were measured; and antral follicle counts (AFCs were recorded.Significantly lower level of AMH was observed in women with bilateral tubal occlusion compared to control group [2.62 (2.95 ng/ml vs. 3.37 (3.11 ng/ml, P = 0.03], and the difference remained after adjustment of BMI (Padjust = 0.04. However, no statistical difference was found in the levels of FSH [7.00 (2.16 IU/L vs. 6.74 (2.30 IU/L], LH [4.18 (1.52 IU/L vs. 4.63 (2.52 IU/L], E2 [35.95 (20.40 pg/ml vs. 34.90 (17.85 pg/ml], T [25.07±11.46 ng/dl vs. 24.84±12.75 ng/dl], and AFC [6.00 (4.00 vs. 7.00 (4.00] between two groups (p>0.05.Women with bilateral tubal occlusion showed decreased AMH level, suggesting that chronic pelvic inflammation may diminish ovarian reserve. More caution should be paid when evaluating the detriment of PID on female fertility.

  19. Chronic Intestinal Inflammation: Inflammatory Bowel Disease and Colitis-Associated Colon Cancer

    Directory of Open Access Journals (Sweden)

    Deborah C. Rubin

    2012-05-01

    Full Text Available The inflammatory bowel diseases (IBD, including Crohn’s disease and ulcerative colitis, are chronic inflammatory disorders of the intestine. The prevalence in the United States is greater than 200 cases per 100,000, with the total number of IBD patients between 1 and 1.5 million. Crohn’s disease may affect all parts of the gastrointestinal tract, from mouth to anus, but most commonly involves the distal part of the small intestine or ileum, and colon. Ulcerative colitis results in colonic inflammation that can affect the rectum only, or can progress proximally to involve part of or the entire colon. Clinical symptoms include diarrhea, abdominal pain, gastrointestinal bleeding and weight loss. A serious long-term complication of chronic inflammation is the development of colorectal cancer. A genetic basis for IBD had long been recognized based on the increased familial risk. However, significant discordance for Crohn’s disease in twins, and a much less robust phenotypic concordance for ulcerative colitis, suggested additional factors play a role in disease pathogenesis, including environmental factors. In the past several years, progress in understanding the molecular basis of IBD has accelerated, beginning with the generation of animal models of colitis and progressing to the identification of specific genetic markers from candidate gene, gene linkage and genome wide association analyses . Genetic studies have also resulted in the recognition of the importance of environmental factors, particularly the crucial role of the gut microbiota in Crohn’s disease and ulcerative colitis. Altered immune responses to the normal intestinal flora are key factors in IBD pathogenesis. In this Research Topic, the genetic basis of IBD, the genetic and cellular alterations associated with colitis-associated colon cancer, and the emerging role of the intestinal microbiota and other environmental factors will be reviewed.

  20. Role of protein tyrosine phosphatases in regulating the immune system: implications for chronic intestinal inflammation.

    Science.gov (United States)

    Spalinger, Marianne R; McCole, Declan F; Rogler, Gerhard; Scharl, Michael

    2015-03-01

    Current hypothesis suggests that genetic, immunological, and bacterial factors contribute essentially to the pathogenesis of inflammatory bowel disease. Variations within the gene loci encoding protein tyrosine phosphatases (PTPs) have been associated with the onset of inflammatory bowel disease. PTPs modulate the activity of their substrates by dephosphorylation of tyrosine residues and are critical for the regulation of fundamental cellular signaling processes. Evidence emerges that expression levels of PTPN2, PTPN11, and PTPN22 are altered in actively inflamed intestinal tissue. PTPN2 seems to be critical for protecting intestinal epithelial barrier function, regulating innate and adaptive immune responses and finally for maintaining intestinal homeostasis. These observations have been confirmed in PTPN2 knockout mice in vivo. Those animals are clearly more susceptible to intestinal and systemic inflammation and feature alterations in innate and adaptive immune responses. PTPN22 controls inflammatory signaling in lymphocytes and mononuclear cells resulting in aberrant cytokine secretion pattern and autophagosome formation. PTPN22 deficiency in vivo results in more severe colitis demonstrating the relevance of PTPN22 for intestinal homeostasis in vivo. Of note, loss of PTPN22 promotes mitogen-activated protein kinase-induced cytokine secretion but limits secretion of nuclear factor κB-associated cytokines and autophagy in mononuclear cells. Loss of PTPN11 is also associated with increased colitis severity in vivo. In summary, dysfunction of those PTPs results in aberrant and uncontrolled immune responses that result in chronic inflammatory conditions. This way, it becomes more and more evident that dysfunction of PTPs displays an important factor in the pathogenesis of chronic intestinal inflammation, in particular inflammatory bowel disease.

  1. Role of protein tyrosine phosphatases in regulating the immune system: implications for chronic intestinal inflammation.

    Science.gov (United States)

    Spalinger, Marianne R; McCole, Declan F; Rogler, Gerhard; Scharl, Michael

    2015-03-01

    Current hypothesis suggests that genetic, immunological, and bacterial factors contribute essentially to the pathogenesis of inflammatory bowel disease. Variations within the gene loci encoding protein tyrosine phosphatases (PTPs) have been associated with the onset of inflammatory bowel disease. PTPs modulate the activity of their substrates by dephosphorylation of tyrosine residues and are critical for the regulation of fundamental cellular signaling processes. Evidence emerges that expression levels of PTPN2, PTPN11, and PTPN22 are altered in actively inflamed intestinal tissue. PTPN2 seems to be critical for protecting intestinal epithelial barrier function, regulating innate and adaptive immune responses and finally for maintaining intestinal homeostasis. These observations have been confirmed in PTPN2 knockout mice in vivo. Those animals are clearly more susceptible to intestinal and systemic inflammation and feature alterations in innate and adaptive immune responses. PTPN22 controls inflammatory signaling in lymphocytes and mononuclear cells resulting in aberrant cytokine secretion pattern and autophagosome formation. PTPN22 deficiency in vivo results in more severe colitis demonstrating the relevance of PTPN22 for intestinal homeostasis in vivo. Of note, loss of PTPN22 promotes mitogen-activated protein kinase-induced cytokine secretion but limits secretion of nuclear factor κB-associated cytokines and autophagy in mononuclear cells. Loss of PTPN11 is also associated with increased colitis severity in vivo. In summary, dysfunction of those PTPs results in aberrant and uncontrolled immune responses that result in chronic inflammatory conditions. This way, it becomes more and more evident that dysfunction of PTPs displays an important factor in the pathogenesis of chronic intestinal inflammation, in particular inflammatory bowel disease. PMID:25581833

  2. The Relationship Between Chronic Inflammation and Glucidic-Lipidic Profile Disorders in Kidney Transplant Recipients

    Directory of Open Access Journals (Sweden)

    Tarța I.D.

    2016-03-01

    Full Text Available Introduction: Chronic inflammation has a proven role in atherogenesis, lipid profile parameters being related to cytokine production. In kidney transplant recipients, interleukin 6 (IL-6 is significantly associated with graft-related outcomes and also alterations of cholesterol and triglyceride metabolism. The aim of this study was to investigate the relationship between chronic inflammation and glucidic-lipidic metabolism disorders in a group of patients with kidney transplantation as renal replacement therapy. Methods: A prospective observational study which enrolled thirtysix non-diabetic kidney transplant recipients was conducted in the Nephrology and Peritoneal Dialysis Department, County Clinic Hospital of Tirgu Mures. The study group was divided as following: recipients with serum IL-6 concentration higher than 3.8 pg/ml (group A and IL-6 within the normal range (group B. Results: Allograft recipients with higher serum IL-6 had significant higher erytrocyte sedimentation rate(ESR, p=0.0067. Patients with over-the-range levels of IL-6 had significant higher levels of serum cholesterol and LDL-cholesterol respectively (p=0.0242 and p=0.0081. Serum Apo-B was also significant higher in Group A than Group B. Protein excretion was significant higher in patients from group A (p=0.0013. No statistical significant relationship could be proven between elevated levels of IL-6 and hbA1c, insulin and glycosuria disturbances in the two groups. Also, we found no statistical significant association between resistivity and pulsatility indices (both hilum and intragraft or carotid intima media thickness. Conclusion: Serum interleukin 6 is related to lipid profile disorders and less to glucidic metabolism anomalies in non-diabetic kidney transplant recipients.

  3. Suppression of basal and carbon nanotube-induced oxidative stress, inflammation and fibrosis in mouse lungs by Nrf2.

    Science.gov (United States)

    Dong, Jie; Ma, Qiang

    2016-08-01

    The lungs are susceptible to oxidative damage by inhaled pathogenic agents, including multi-walled carbon nanotubes (MWCNT). The nuclear factor erythroid 2-related factor 2 (Nrf2) has been implicated in regulating the body's defense against oxidative stress. Here, we analyzed the function of Nrf2 in the lungs. Under a basal condition, Nrf2 knockout (KO) mice showed apparent pulmonary infiltration of granulocytes, macrophages and B and T lymphocytes, and elevated deposition of collagen fibers. Exposure to MWCNT (XNRI MWNT-7, Mitsui, Tokyo, Japan) by pharyngeal aspiration elicited rapid inflammatory and fibrotic responses in a dose (0, 5, 20 and 40 μg) and time (1, 3, 7 and 14 d)-dependent manner. The responses reached peak levels on day 7 post-exposure to 40 μg MWCNT, evidenced by massive inflammatory infiltration and formation of inflammatory and fibrotic foci, which were more evident in Nrf2 KO than wild-type (WT) lungs. At the molecular level, Nrf2 protein was detected at a low level under a basal condition, and was dramatically increased by MWCNT in WT, but not Nrf2 KO, lungs. Activation of Nrf2 was inversely correlated with induced expression of fibrosis marker genes and profibrotic cytokines. Furthermore, the levels of ROS and oxidative stress were remarkably higher in Nrf2 KO than WT lungs under a physiological condition, and were dramatically increased by MWCNT, with the increase significantly more striking in KO lungs. The findings reveal that Nrf2 plays an important role in suppressing the basal and MWCNT-induced oxidant production, inflammation and fibrosis in the lungs, thereby protecting against MWCNT lung toxicity. PMID:26592091

  4. Attenuation of acute nitrogen mustard-induced lung injury, inflammation and fibrogenesis by a nitric oxide synthase inhibitor

    International Nuclear Information System (INIS)

    Nitrogen mustard (NM) is a toxic vesicant known to cause damage to the respiratory tract. Injury is associated with increased expression of inducible nitric oxide synthase (iNOS). In these studies we analyzed the effects of transient inhibition of iNOS using aminoguanidine (AG) on NM-induced pulmonary toxicity. Rats were treated intratracheally with 0.125 mg/kg NM or control. Bronchoalveolar lavage fluid (BAL) and lung tissue were collected 1 d–28 d later and lung injury, oxidative stress and fibrosis assessed. NM exposure resulted in progressive histopathological changes in the lung including multifocal lesions, perivascular and peribronchial edema, inflammatory cell accumulation, alveolar fibrin deposition, bronchiolization of alveolar septal walls, and fibrosis. This was correlated with trichrome staining and expression of proliferating cell nuclear antigen (PCNA). Expression of heme oxygenase (HO)-1 and manganese superoxide dismutase (Mn-SOD) was also increased in the lung following NM exposure, along with levels of protein and inflammatory cells in BAL, consistent with oxidative stress and alveolar-epithelial injury. Both classically activated proinflammatory (iNOS+ and cyclooxygenase-2+) and alternatively activated profibrotic (YM-1+ and galectin-3+) macrophages appeared in the lung following NM administration; this was evident within 1 d, and persisted for 28 d. AG administration (50 mg/kg, 2 ×/day, 1 d–3 d) abrogated NM-induced injury, oxidative stress and inflammation at 1 d and 3 d post exposure, with no effects at 7 d or 28 d. These findings indicate that nitric oxide generated via iNOS contributes to acute NM-induced lung toxicity, however, transient inhibition of iNOS is not sufficient to protect against pulmonary fibrosis. -- Highlights: ► Nitrogen mustard (NM) induces acute lung injury and fibrosis. ► Pulmonary toxicity is associated with increased expression of iNOS. ► Transient inhibition of iNOS attenuates acute lung injury induced by

  5. Attenuation of acute nitrogen mustard-induced lung injury, inflammation and fibrogenesis by a nitric oxide synthase inhibitor

    Energy Technology Data Exchange (ETDEWEB)

    Malaviya, Rama; Venosa, Alessandro [Department of Pharmacology and Toxicology, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, NJ 08854 (United States); Hall, LeRoy [Drug Safety Sciences, Johnson and Johnson, Raritan, NJ 08869 (United States); Gow, Andrew J. [Department of Pharmacology and Toxicology, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, NJ 08854 (United States); Sinko, Patrick J. [Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, NJ 08854 (United States); Laskin, Jeffrey D. [Department of Environmental and Occupational Medicine, UMDNJ-Robert Wood Johnson Medical School, Piscataway, NJ 08854 (United States); Laskin, Debra L., E-mail: laskin@eohsi.rutgers.edu [Department of Pharmacology and Toxicology, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, NJ 08854 (United States)

    2012-12-15

    Nitrogen mustard (NM) is a toxic vesicant known to cause damage to the respiratory tract. Injury is associated with increased expression of inducible nitric oxide synthase (iNOS). In these studies we analyzed the effects of transient inhibition of iNOS using aminoguanidine (AG) on NM-induced pulmonary toxicity. Rats were treated intratracheally with 0.125 mg/kg NM or control. Bronchoalveolar lavage fluid (BAL) and lung tissue were collected 1 d–28 d later and lung injury, oxidative stress and fibrosis assessed. NM exposure resulted in progressive histopathological changes in the lung including multifocal lesions, perivascular and peribronchial edema, inflammatory cell accumulation, alveolar fibrin deposition, bronchiolization of alveolar septal walls, and fibrosis. This was correlated with trichrome staining and expression of proliferating cell nuclear antigen (PCNA). Expression of heme oxygenase (HO)-1 and manganese superoxide dismutase (Mn-SOD) was also increased in the lung following NM exposure, along with levels of protein and inflammatory cells in BAL, consistent with oxidative stress and alveolar-epithelial injury. Both classically activated proinflammatory (iNOS{sup +} and cyclooxygenase-2{sup +}) and alternatively activated profibrotic (YM-1{sup +} and galectin-3{sup +}) macrophages appeared in the lung following NM administration; this was evident within 1 d, and persisted for 28 d. AG administration (50 mg/kg, 2 ×/day, 1 d–3 d) abrogated NM-induced injury, oxidative stress and inflammation at 1 d and 3 d post exposure, with no effects at 7 d or 28 d. These findings indicate that nitric oxide generated via iNOS contributes to acute NM-induced lung toxicity, however, transient inhibition of iNOS is not sufficient to protect against pulmonary fibrosis. -- Highlights: ► Nitrogen mustard (NM) induces acute lung injury and fibrosis. ► Pulmonary toxicity is associated with increased expression of iNOS. ► Transient inhibition of iNOS attenuates acute

  6. Role of CD14 in a mouse model of acute lung inflammation induced by different lipopolysaccharide chemotypes.

    Directory of Open Access Journals (Sweden)

    Adam A Anas

    Full Text Available BACKGROUND: Recognition of lipopolysaccharide (LPS is required for effective defense against invading gram-negative bacteria. Recently, in vitro studies revealed that CD14 is required for activation of the myeloid differentiation factor (MyD88-dependent Toll-like receptor (TLR4 signaling pathway by smooth (S-LPS, but not by rough (R-LPS. The present study investigated the role of CD14 in induction of lung inflammation in mice by these different LPS chemotypes. METHODOLOGY/RESULTS: Neutrophil accumulation and tumor necrosis factor (TNF release in bronchoalveolar lavage fluid were determined 6 hours after intranasal treatment of wild type (WT and CD14 knock-out (KO mice with different doses S-LPS or R-LPS. The contribution of CD14 to lung inflammation induced by S-LPS or R-LPS depended on the LPS dose. At low doses, S-LPS and R-LPS induced neutrophil influx in a CD14-dependent manner. Low dose S-LPS-induced cytokine release also depended on CD14. Strikingly, neutrophil influx and TNF release induced by high dose S-LPS or R-LPS was diminished in the presence of CD14. Intranasal administration of sCD14 to CD14 KO mice treated with S-LPS partially reversed the inflammatory response to the response observed in WT mice. CONCLUSIONS: In conclusion, CD14 modulates effects of both S-LPS and R-LPS within the lung in a similar way. Except for R-LPS-induced TNF release, S-LPS and R-LPS at low dose induced acute lung inflammation in a CD14-dependent manner, while the inflammatory response triggered by high dose S-LPS or R-LPS was diminished by CD14.

  7. Ex vivo adenoviral vector gene delivery results in decreased vector-associated inflammation pre- and post-lung transplantation in the pig.

    Science.gov (United States)

    Yeung, Jonathan C; Wagnetz, Dirk; Cypel, Marcelo; Rubacha, Matthew; Koike, Terumoto; Chun, Yi-Min; Hu, Jim; Waddell, Thomas K; Hwang, David M; Liu, Mingyao; Keshavjee, Shaf

    2012-06-01

    Acellular normothermic ex vivo lung perfusion (EVLP) is a novel method of donor lung preservation for transplantation. As cellular metabolism is preserved during perfusion, it represents a potential platform for effective gene transduction in donor lungs. We hypothesized that vector-associated inflammation would be reduced during ex vivo delivery due to isolation from the host immune system response. We compared ex vivo with in vivo intratracheal delivery of an E1-, E3-deleted adenoviral vector encoding either green fluorescent protein (GFP) or interleukin-10 (IL-10) to porcine lungs. Twelve hours after delivery, the lung was transplanted and the post-transplant function assessed. We identified significant transgene expression by 12 hours in both in vivo and ex vivo delivered groups. Lung function remained excellent in all ex vivo groups after viral vector delivery; however, as expected, lung function decreased in the in vivo delivered adenovirus vector encoding GFP (AdGFP) group with corresponding increases in IL-1β levels. Transplanted lung function was excellent in the ex vivo transduced lungs and inferior lung function was seen in the in vivo group after transplantation. In summary, ex vivo delivery of adenoviral gene therapy to the donor lung is superior to in vivo delivery in that it leads to less vector-associated inflammation and provides superior post-transplant lung function. PMID:22453765

  8. Ex Vivo Adenoviral Vector Gene Delivery Results in Decreased Vector-associated Inflammation Pre- and Post–lung Transplantation in the Pig

    Science.gov (United States)

    Yeung, Jonathan C; Wagnetz, Dirk; Cypel, Marcelo; Rubacha, Matthew; Koike, Terumoto; Chun, Yi-Min; Hu, Jim; Waddell, Thomas K; Hwang, David M; Liu, Mingyao; Keshavjee, Shaf

    2012-01-01

    Acellular normothermic ex vivo lung perfusion (EVLP) is a novel method of donor lung preservation for transplantation. As cellular metabolism is preserved during perfusion, it represents a potential platform for effective gene transduction in donor lungs. We hypothesized that vector-associated inflammation would be reduced during ex vivo delivery due to isolation from the host immune system response. We compared ex vivo with in vivo intratracheal delivery of an E1-, E3-deleted adenoviral vector encoding either green fluorescent protein (GFP) or interleukin-10 (IL-10) to porcine lungs. Twelve hours after delivery, the lung was transplanted and the post-transplant function assessed. We identified significant transgene expression by 12 hours in both in vivo and ex vivo delivered groups. Lung function remained excellent in all ex vivo groups after viral vector delivery; however, as expected, lung function decreased in the in vivo delivered adenovirus vector encoding GFP (AdGFP) group with corresponding increases in IL-1β levels. Transplanted lung function was excellent in the ex vivo transduced lungs and inferior lung function was seen in the in vivo group after transplantation. In summary, ex vivo delivery of adenoviral gene therapy to the donor lung is superior to in vivo delivery in that it leads to less vector-associated inflammation and provides superior post-transplant lung function. PMID:22453765

  9. Mesenchymal Stem Cell Attenuates Neutrophil-predominant Inflammation and Acute Lung Injury in an In Vivo Rat Model of Ventilator-induced Lung Injury

    Directory of Open Access Journals (Sweden)

    Tian-Shun Lai

    2015-01-01

    Full Text Available Background: Subsequent neutrophil (polymorphonuclear neutrophil [PMN]-predominant inflammatory response is a predominant feature of ventilator-induced lung injury (VILI, and mesenchymal stem cell (MSC can improve mice survival model of endotoxin-induced acute lung injury, reduce lung impairs, and enhance the repair of VILI. However, whether MSC could attenuate PMN-predominant inflammatory in the VILI is still unknown. This study aimed to test whether MSC intervention could attenuate the PMN-predominate inflammatory in the mechanical VILI. Methods: Sprague-Dawley rats were ventilated for 2 hours with large tidal volume (20 mL/kg. MSCs were given before or after ventilation. The inflammatory chemokines and gas exchange were observed and compared dynamically until 4 hours after ventilation, and pulmonary pathological change and activation of PMN were observed and compared 4 hours after ventilation. Results: Mechanical ventilation (MV caused significant lung injury reflected by increasing in PMN pulmonary sequestration, inflammatory chemokines (tumor necrosis factor-alpha, interleukin-6 and macrophage inflammatory protein 2 in the bronchoalveolar lavage fluid, and injury score of the lung tissue. These changes were accompanied with excessive PMN activation which reflected by increases in PMN elastase activity, production of radical oxygen series. MSC intervention especially pretreatment attenuated subsequent lung injury, systemic inflammation response and PMN pulmonary sequestration and excessive PMN activation initiated by injurious ventilation. Conclusions: MV causes profound lung injury and PMN-predominate inflammatory responses. The protection effect of MSC in the VILI rat model is related to the suppression of the PMN activation.

  10. Mesenchymal Stem Cell Attenuates Neutrophil-predominant Inflammation and Acute Lung Injury in an In Vivo Rat Model of Ventilator-induced Lung Injury

    Institute of Scientific and Technical Information of China (English)

    Tian-Shun Lai; Zhi-Hong Wang; Shao-Xi Cai

    2015-01-01

    Background:Subsequent neutrophil (polymorphonuclear neutrophil [PMN])-predominant inflammatory response is a predominant feature of ventilator-induced lung injury (VILI),and mesenchymal stem cell (MSC) can improve mice survival model of endotoxin-induced acute lung injury,reduce lung impairs,and enhance the repair of VILI.However,whether MSC could attenuate PMN-predominant inflammatory in the VILI is still unknown.This study aimed to test whether MSC intervention could attenuate the PMN-predominate inflammatory in the mechanical VILI.Methods:Sprague-Dawley rats were ventilated for 2 hours with large tidal volume (20 mL/kg).MSCs were given before or after ventilation.The inflammatory chemokines and gas exchange were observed and compared dynamically until 4 hours after ventilation,and pulmonary pathological change and activation of PMN were observed and compared 4 hours after ventilation.Results:Mechanical ventilation (MV) caused significant lung injury reflected by increasing in PMN pulmonary sequestration,inflammatory chemokines (tumor necrosis factor-alpha,interleukin-6 and macrophage inflammatory protein 2) in the bronchoalveolar lavage fluid,and injury score of the lung tissue.These changes were accompanied with excessive PMN activation which reflected by increases in PMN elastase activity,production of radical oxygen series.MSC intervention especially pretreatment attenuated subsequent lung injury,systemic inflammation response and PMN pulmonary sequestration and excessive PMN activation initiated by injurious ventilation.Conclusions:MV causes profound lung injury and PMN-predominate inflammatory responses.The protection effect of MSC in the VILI rat model is related to the suppression of the PMN activation.

  11. Characterization of inflammation in COPD : clinical and experimental approach

    NARCIS (Netherlands)

    Vernooy, J.H.J.

    2003-01-01

    Chronic inflammation is an important feature of COPD. This inflammatory response is not restricted to the local compartment - including airways, lung parenchyma, and pulmonary vasculature - but is also present in the circulation. However, the origin of the systemic inflammation present in COPD patie

  12. Chronic Alcohol Ingestion in Rats Alters Lung Metabolism, Promotes Lipid Accumulation, and Impairs Alveolar Macrophage Functions

    Science.gov (United States)

    Romero, Freddy; Shah, Dilip; Duong, Michelle; Stafstrom, William; Hoek, Jan B.; Kallen, Caleb B.; Lang, Charles H.

    2014-01-01

    Chronic alcoholism impairs pulmonary immune homeostasis and predisposes to inflammatory lung diseases, including infectious pneumonia and acute respiratory distress syndrome. Although alcoholism has been shown to alter hepatic metabolism, leading to lipid accumulation, hepatitis, and, eventually, cirrhosis, the effects of alcohol on pulmonary metabolism remain largely unknown. Because both the lung and the liver actively engage in lipid synthesis, we hypothesized that chronic alcoholism would impair pulmonary metabolic homeostasis in ways similar to its effects in the liver. We reasoned that perturbations in lipid metabolism might contribute to the impaired pulmonary immunity observed in people who chronically consume alcohol. We studied the metabolic consequences of chronic alcohol consumption in rat lungs in vivo and in alveolar epithelial type II cells and alveolar macrophages (AMs) in vitro. We found that chronic alcohol ingestion significantly alters lung metabolic homeostasis, inhibiting AMP-activated protein kinase, increasing lipid synthesis, and suppressing the expression of genes essential to metabolizing fatty acids (FAs). Furthermore, we show that these metabolic alterations promoted a lung phenotype that is reminiscent of alcoholic fatty liver and is characterized by marked accumulation of triglycerides and free FAs within distal airspaces, AMs, and, to a lesser extent, alveolar epithelial type II cells. We provide evidence that the metabolic alterations in alcohol-exposed rats are mechanistically linked to immune impairments in the alcoholic lung: the elevations in FAs alter AM phenotypes and suppress both phagocytic functions and agonist-induced inflammatory responses. In summary, our work demonstrates that chronic alcohol ingestion impairs lung metabolic homeostasis and promotes pulmonary immune dysfunction. These findings suggest that therapies aimed at reversing alcohol-related metabolic alterations might be effective for preventing and

  13. Influence of Hepatic Inflammation on FibroScan Findings in Diagnosing Fibrosis in Patients with Chronic Hepatitis B.

    Science.gov (United States)

    Zeng, Xianghua; Xu, Cheng; He, Dengming; Zhang, Huiyan; Xia, Jie; Shi, Dairong; Kong, Lingjun; He, Xiaoqin; Wang, Yuming

    2015-06-01

    Hepatic inflammation may affect the performance of FibroScan. This prospective study investigated the influence of hepatic inflammation on liver stiffness measurement (LSM) values by assessing FibroScan and liver biopsy findings in 325 patients with chronic hepatitis B. Liver fibrosis and inflammation were classified into five stages (S0-S4) and grades (G0-G4) according to the Scheuer scoring system. LSM values were correlated with fibrosis stage and inflammation grade (r = 0.479, p 0.05). For inflammation grades G0, G1, G2 and G3, areas under receiver operating characteristic curves of FibroScan for significant fibrosis were 0.8267 (p < 0.001), 0.6956 (p < 0.001), 0.709 (p = 0.0012) and 0.6947 (p = 0.137), respectively. Inflammation has a significant influence on LSM values in patients with chronic hepatitis B with mild fibrosis, but not in those with significant fibrosis.

  14. Increasing Prevalence of Chronic Lung Disease in Veterans of the Wars in Iraq and Afghanistan.

    Science.gov (United States)

    Pugh, Mary Jo; Jaramillo, Carlos A; Leung, Kar-Wei; Faverio, Paola; Fleming, Nicholas; Mortensen, Eric; Amuan, Megan E; Wang, Chen-Pin; Eapen, Blessen; Restrepo, Marcos; Morris, Michael J

    2016-05-01

    Research from the wars in Afghanistan and Iraq have focused on traumatic brain injury (TBI) and mental health conditions; however, it is becoming clear that other health concerns, such as respiratory illnesses, warrant further scientific inquiry. Early reports from theater and postdeployment health assessments suggested an association with deployment-related exposures (e.g., sand, burn pits, chemical, etc.) and new-onset respiratory symptoms. We used data from Veterans Affairs medical encounters between fiscal years 2003 and 2011 to identify trends in chronic obstructive pulmonary disease, asthma, and interstitial lung disease in veterans. We used data from Veterans Affairs and Department of Defense sources to identify sociodemographic (age, sex, race), military (e.g., service branch, multiple deployments) and clinical characteristics (TBI, smoking) of individuals with and without chronic lung diseases. Generalized estimating equations found significant increases over time for chronic obstructive pulmonary disease and asthma in both unadjusted and adjusted analyses. Trends for interstitial lung disease were significant only in adjusted analyses. Age, smoking, and TBI were also significantly associated with chronic lung diseases; however, multiple deployments were not associated. Research is needed to identify which characteristics of deployment-related exposures are linked with chronic lung disease. PMID:27136656

  15. Effects of liver inflammation on FibroScan diagnosis of hepatic fibrosis in patients with chronic hepatitis B

    Institute of Scientific and Technical Information of China (English)

    刘志权

    2013-01-01

    Objective To investigate the influence of liver inflammation on the ability of the FibroScan non-invasive elastrography scanner to diagnose hepatic fibrosis in patients with chronic hepatitis B (CHB) .Methods A total of 124 CHB patients who received liver biopsy and concomitant liver stiffness measurement (LSM) by FibroScan

  16. Protective actions of green tea polyphenols and alfacalcidol on bone microstructure in female rats with chronic inflammation

    Science.gov (United States)

    This study investigated the effects of green tea polyphenols (GTP) and alfacalcidol on bone microstructure and strength along with possible mechanisms in rats with chronic inflammation. A 12-week study using a 2 (no GTP vs. 0.5%, w/v GTP in drinking water) × 2 (no alfacalcidol vs. 0.05 ug/kg alfacal...

  17. Slit2 regulates attractive eosinophil and repulsive neutrophil chemotaxis through differential srGAP1 expression during lung inflammation.

    Science.gov (United States)

    Ye, Bu-Qing; Geng, Zhen H; Ma, Li; Geng, Jian-Guo

    2010-11-15

    Directional migration of leukocytes is an essential step in leukocyte trafficking during inflammatory responses. However, the molecular mechanisms governing directional chemotaxis of leukocytes remain poorly understood. The Slit family of guidance cues has been implicated for inhibition of leuocyte migration. We report that Clara cells in the bronchial epithelium secreted Slit2, whereas eosinophils and neutrophils expressed its cell-surface receptor, Robo1. Compared to neutrophils, eosinophils exhibited a significantly lower level of Slit-Robo GTPase-activating protein 1 (srGAP1), leading to activation of Cdc42, recruitment of PI3K to Robo1, enhancment of eotaxin-induced eosinophil chemotaxis, and exaggeration of allergic airway inflammation. Notably, OVA sensitization elicited a Slit2 gradient at so-called bronchus-alveoli axis, with a higher level of Slit2 in the bronchial epithelium and a lower level in the alveolar tissue. Aerosol administration of rSlit2 accelerated eosinophil infiltration, whereas i.v. administered Slit2 reduced eosinophil deposition. In contrast, Slit2 inactivated Cdc42 and suppressed stromal cell-derived factor-1α-induced chemotaxis of neutrophils for inhibiting endotoxin-induced lung inflammation, which were reversed by blockade of srGAP1 binding to Robo1. These results indicate that the newly identified Slit2 gradient at the bronchus-alveoli axis induces attractive PI3K signaling in eosinophils and repulsive srGAP1 signaling in neutrophils through differential srGAP1 expression during lung inflammation.

  18. Correlation of alkaline phosphatase activity to clinical parameters of inflammation in smokers suffering from chronic periodontitis

    Science.gov (United States)

    Grover, Vishakha; Malhotra, Ranjan; Kapoor, Anoop; Bither, Rupika; Sachdeva, Sonia

    2016-01-01

    Context: Current clinical periodontal diagnostic techniques emphasize the assessment of clinical and radiographic signs of periodontal diseases which can provide a measure of history of disease. Hence, new methodologies for early identification and determination of periodontal disease activity need to be explored which will eventually result in expedited treatment. Aim: To evaluate the correlation of alkaline phosphatase (ALP) activity in gingival crevicular fluid (GCF) to clinical parameters of periodontal inflammation in smokers with chronic periodontitis. Materials and Methods: Study population included 15 smoker male patients in the age group of 35–55 years suffering from moderate generalized chronic periodontitis with history of smoking present. Following parameters were evaluated at baseline, 1 month and 3 months after scaling and root planing: plaque index, bleeding index, probing pocket depth (PD), relative attachment level (RAL), and GCF ALP activity. Statistical Analysis Used: Independent variables for measurements over time were analyzed by using Wilcoxon signed rank test. Results: A statistically significant reduction in all the clinical parameters and GCF ALP activity was observed from baseline to 1 month and 3 months. A correlation was observed between change in GCF ALP activity and PD reduction as well as gain in RAL at 3 months. Conclusion: The present study emphasizes that total ALP activity could be used as a marker for periodontal disease activity in smokers. Estimation of changes in the levels of this enzyme has a potential to aid in the detection of progression of periodontal disease and monitoring the response to periodontal therapy. PMID:27563197

  19. Correlation of alkaline phosphatase activity to clinical parameters of inflammation in smokers suffering from chronic periodontitis

    Directory of Open Access Journals (Sweden)

    Vishakha Grover

    2016-01-01

    Full Text Available Context: Current clinical periodontal diagnostic techniques emphasize the assessment of clinical and radiographic signs of periodontal diseases which can provide a measure of history of disease. Hence, new methodologies for early identification and determination of periodontal disease activity need to be explored which will eventually result in expedited treatment. Aim: To evaluate the correlation of alkaline phosphatase (ALP activity in gingival crevicular fluid (GCF to clinical parameters of periodontal inflammation in smokers with chronic periodontitis. Materials and Methods: Study population included 15 smoker male patients in the age group of 35–55 years suffering from moderate generalized chronic periodontitis with history of smoking present. Following parameters were evaluated at baseline, 1 month and 3 months after scaling and root planing: plaque index, bleeding index, probing pocket depth (PD, relative attachment level (RAL, and GCF ALP activity. Statistical Analysis Used: Independent variables for measurements over time were analyzed by using Wilcoxon signed rank test. Results: A statistically significant reduction in all the clinical parameters and GCF ALP activity was observed from baseline to 1 month and 3 months. A correlation was observed between change in GCF ALP activity and PD reduction as well as gain in RAL at 3 months. Conclusion: The present study emphasizes that total ALP activity could be used as a marker for periodontal disease activity in smokers. Estimation of changes in the levels of this enzyme has a potential to aid in the detection of progression of periodontal disease and monitoring the response to periodontal therapy.

  20. MBOAT7 rs641738 increases risk of liver inflammation and transition to fibrosis in chronic hepatitis C

    Science.gov (United States)

    Thabet, Khaled; Asimakopoulos, Anastasia; Shojaei, Maryam; Romero-Gomez, Manuel; Mangia, Alessandra; Irving, William L.; Berg, Thomas; Dore, Gregory J.; Grønbæk, Henning; Sheridan, David; Abate, Maria Lorena; Bugianesi, Elisabetta; Weltman, Martin; Mollison, Lindsay; Cheng, Wendy; Riordan, Stephen; Fischer, Janett; Spengler, Ulrich; Nattermann, Jacob; Wahid, Ahmed; Rojas, Angela; White, Rose; Douglas, Mark W.; McLeod, Duncan; Powell, Elizabeth; Liddle, Christopher; van der Poorten, David; George, Jacob; Eslam, Mohammed; Gallego-Duran, Rocio; Applegate, Tanya; Bassendine, Margaret; Rosso, Chiara; Mezzabotta, Lavinia; Leung, Reynold; Malik, Barbara; Matthews, Gail; Grebely, Jason; Fragomeli, Vincenzo; Jonsson, Julie R.; Santaro, Rosanna

    2016-01-01

    Cirrhosis likely shares common pathophysiological pathways despite arising from a variety of liver diseases. A recent GWAS identified rs641738, a polymorphism in the MBOAT7 locus, as being associated with the development of alcoholic cirrhosis. Here we explore the role of this variant on liver inflammation and fibrosis in two cohorts of patients with chronic hepatitis C. In 2,051 patients, rs641738 associated with severe hepatic inflammation and increased risk of fibrosis, as well as fast fibrosis progression. At functional level, rs641738 associated with MBOAT7 transcript and protein levels in liver and blood, and with serum inflammatory, oxidative stress and macrophage activation markers. MBOAT7 was expressed in immune cell subsets, implying a role in hepatic inflammation. We conclude that the MBOAT7 rs641738 polymorphism is a novel risk variant for liver inflammation in hepatitis C, and thereby for liver fibrosis. PMID:27630043

  1. The role of chronic inflammation in the development of gastrointestinal cancers: reviewing cancer prevention with natural anti-inflammatory intervention.

    Science.gov (United States)

    Lee, Ho-Jae; Park, Jong-Min; Han, Young Min; Gil, Hong Kwon; Kim, Jinhyung; Chang, Ji Young; Jeong, Migyeong; Go, Eun-Jin; Hahm, Ki Baik

    2016-01-01

    Inflammatory mediators alter the local environment of tumors, known as the tumor microenvironment. Mechanistically, chronic inflammation induces DNA damage, but understanding this hazard may help in the search for new chemopreventive agents for gastrointestinal (GI) cancer which attenuate inflammation. In the clinic, GI cancer still remains a major cause of cancer-associated mortality, chemoprevention with anti-inflammatory agents is thought to be a realistic approach to reduce GI cancer. Proton pump inhibitors, monoclonal antibodies targeting tumor necrosis factor-alpha, anti-sense targeted smad7 and non-steroidal anti-inflammatory agents have been investigated for their potential to prevent inflammation-based GI cancer. Besides these, a wide variety of natural products have also shown potential for the prevention of GI cancer. In this review, the authors will provide insights to explain the mechanistic connection between inflammation and GI cancer, as well as describe a feasible cancer prevention strategy based on anti-inflammatory treatments.

  2. Effect of bone marrow derived mesenchymal stem cells on lung pathology and inflammation in ovalbumin-induced asthma in mouse

    Directory of Open Access Journals (Sweden)

    Maryam Mohammadian

    2016-01-01

    Full Text Available Objective(s:Bone marrow-derived mesenchymal stem cells (BMSCs have attracted significant interest to treat asthma and its complication. In this study, the effects of BMSCs on lung pathology and inflammation in an ovalbumin-induced asthma model in mouse were examined. Materials and Methods:BALB/c mice were divided into three groups: control group (animals were not sensitized, asthma group (animals were sensitized by ovalbumin, asthma+BMSC group (animals were sensitized by ovalbumin and treated with BMSCs. BMSCs were isolated and characterized and then labeled with Bromodeoxyuridine (BrdU. After that the cells transferred into asthmatic mice. Histopathological changes of the airways, BMSCs migration and total and differential white blood cell (WBC count in bronchoalveolar lavage (BAL fluid were evaluated. Results:A large number of BrdU-BMSCs were found in the lungs of mice treated with BMSCs. The histopathological changes, BAL total WBC counts and the percentage of neutrophils and eosinophils were increased in asthma group compared to the control group. Treatment with BMSCs significantly decreased airway pathological indices, inflammatory cell infiltration, and also goblet cell hyperplasia. Conclusion:The results of this study revealed that BMSCs therapy significantly suppressed the lung pathology and inflammation in the ovalbumin induced asthma model in mouse.

  3. Darbepoetin alpha reduces oxidative stress and chronic inflammation in atherosclerotic lesions of apo E deficient mice in experimental renal failure.

    Directory of Open Access Journals (Sweden)

    Nicole Arend

    Full Text Available BACKGROUND: Cardiovascular morbidity and mortality is very important in patients with chronic renal failure. This occurs even in mild impairment of renal function and may be related to oxidative stress and chronic inflammation. The nephrectomized apo E knockout mouse is an accepted model for evaluating atherosclerosis in renal dysfunction. Erythropoietin derivates showed anti-oxidative and anti-inflammatory effects. Therefore, this study evaluates the effects of Darbepoetin on markers of oxidative stress and chronic inflammation in atherosclerotic lesions in apo E knockout mice with renal dysfunction. METHODS: Apo E knockout mice underwent unilateral (Unx, n = 20 or subtotal (Snx, n = 26 nephrectomy or sham operation (Sham, n = 16. Mice of each group were either treated with Darbepoetin or saline solution, a part of Snx mice received a tenfold higher dose of Darbepoetin. The aortic plaques were measured and morphologically characterized. Additional immunhistochemical analyses were performed on tissue samples taken from the heart and the aorta. RESULTS: Both Unx and Snx mice showed increased expression of markers of oxidative stress and chronic inflammation. While aortic plaque size was not different, Snx mice showed advanced plaque stages when compared to Unx mice. Darbepoetin treatment elevated hematocrit and lowered Nitrotyrosin as one marker of oxidative stress, inflammation in heart and aorta, plaque stage and in the high dose even plaque cholesterol content. In contrast, there was no influence of Darbepoetin on aortic plaque size; high dose Darbepoetin treatment resulted in elevated renal serum parameters. CONCLUSION: Darbepoetin showed some protective cardiovascular effects irrespective of renal function, i.e. it improved plaque structure and reduced some signs of oxidative stress and chronic inflammation without affecting plaque size. Nevertheless, the dose dependent adverse effects must be considered as high Darbepoetin treatment

  4. Peripheral Tc17 and Tc17/Interferon-γ Cells are Increased and Associated with Lung Function in Patients with Chronic Obstructive Pulmonary Disease

    OpenAIRE

    Wei-Han Xu; Xiao-Ling Hu; Xiao-Fang Liu; Peng Bai; Yong-Chang Sun

    2016-01-01

    Background: Chronic obstructive pulmonary disease (COPD) is characterized by progressive loss of lung function and local and systemic inflammation, in which CD8+ T-cells are believed to play a key role. Activated CD8+ T-cells differentiate into distinct subpopulations, including interferon-γ (IFN-γ)-producing Tc1 and interleukin (IL)-17-producing Tc17 cells. Recent evidence indicates that Tc17 cells exhibit considerable plasticity and may convert into IL-17/IFN-γ-double producing (Tc17/IFN-γ)...

  5. Morphological findings in lungs of the horses with chronic obstructive pulmonary disease (COPD)

    OpenAIRE

    Marinković Darko; Sanja Aleksić-Kovačević; Plamenac P.

    2007-01-01

    The frequency and characteristics of chronic obstructive pulmonary disease (COPD) based on morphological and cytological changes in equine lungs were studied in this paper. Lungs obtained from 51 horses of different age and sex were examined grossly and tissue samples were collected for pathohistological examination. Cytological examination was done on impression smears from the tracheal bifurcation. Pathohistological preparations were stained with hematoxylin eosin (HE), toluidine blue (TB),...

  6. Regional structure-function correlations in chronic obstructive lung disease measured with positron emission tomography.

    OpenAIRE

    Brudin, L H; Rhodes, C G; Valind, S O; Buckingham, P D; Jones, T; Hughes, J. M.

    1992-01-01

    BACKGROUND: Positron emission tomography, performed with isotopes of very short half life, can be used to relate local lung tissue density to local ventilation and to the ventilation:perfusion ratio. This method has been used in 10 patients with severe chronic airflow obstruction and differing values for carbon monoxide transfer factor (TLCO) and transfer coefficient (KCO). METHODS: Ventilation (VA) and the ventilation:perfusion ratio (V/Q), lung density, and blood volume were measured region...

  7. Noninvasive Investigations for the Early Detection of Chronic Airways Dysfunction Following Lung Transplantation

    OpenAIRE

    Cook, Richard C.; Guy Fradet; Nestor L Muller; Daniel F Worsley; David Ostrow; Levy, Robert D

    2003-01-01

    BACKGROUND: The diagnosis of chronic rejection after lung transplantation is limited by the lack of a reliable test to detect airways disease early.OBJECTIVES: To determine whether maximum midexpiratory flow (MMEF), or changes on high resolution computed tomography (HRCT) or ventilation/perfusion lung (V/Q) scans are sensitive and specific for early detection of bronchiolitis obliterans syndrome (BOS; forced expiratory volume in 1 s [FEV1] less than 80% post-transplant baseline) by evaluating...

  8. [Continuous positive airway pressure and high-frequency independent lung ventilation in patients with chronic obstructive lung diseases].

    Science.gov (United States)

    Fedorova, E A; Vyzhigina, M A; Gal'perin, Iu S; Zhukova, S G; Titov, V A; Godin, A V

    2004-01-01

    The original hypoxemia, hypercapnia, high pulmonary hypertension, high resistance of microcirculation vessels, right volumetric ventricular overload, persistent sub-edema of pulmonary intersticium as well as disparity of ventilation and perfusion between both lungs are the main problems in patients with chronic obstructive disease of the lungs (CODL). Such patients are, as a rule, intolerant to the independent lung collaboration or artificial single-stage ventilation (ASV). Patients with respiratory insufficiency, stages 2 and 3, and with a pronounced impaired type of ventilation have originally a deranged blood gas composition, like hypoxemia or hypercapnia. The application of volume-controllable bi-pulmonary ASV in such patients maintains an adequate gas exchange hemodynamics. However, ASV is accompanied by a significantly reduced gas-exchange function of the single ventilated lung and by essentially worsened intrapulmonary hemodynamics. Therefore, what is needed is to use alternative methods of independent lung ventilation in order to eliminate the gas-exchange impairments and to enable surgical interventions at thoracic organs in such patients (who are intolerant to ASV). A choice of a method and means of oxygen supply to the independent lung is of great importance. The possibility to avoid a high pressure in the airways, while maintaining, simultaneously, an adequate gas exchange, makes the method related with maintaining a constant positive pressure in the airways (CPPA) a priority one in case of CODL patients. The use of constant high-frequency ventilation in the independent lung in patients with obstructive pulmonary lesions does not improve the gas exchange or hemodynamics. Simultaneously, a growing total pulmonary resistance and an increasing pressure in the pulmonary artery are observed. Consequently, the discussed method must not be used for the ventilation support of the independent lung in patients with the obstructive type of the impaired external

  9. Proteomic Analysis of Lung Tissue in a Rat Acute Lung Injury Model: Identification of PRDX1 as a Promoter of Inflammation

    Directory of Open Access Journals (Sweden)

    Dongdong Liu

    2014-01-01

    Full Text Available Acute respiratory distress syndrome (ARDS remains a high morbidity and mortality disease entity in critically ill patients, despite decades of numerous investigations into its pathogenesis. To obtain global protein expression changes in acute lung injury (ALI lung tissues, we employed a high-throughput proteomics method to identify key components which may be involved in the pathogenesis of ALI. In the present study, we analyzed lung tissue proteomes of Pseudomonas aeruginosa-induced ALI rats and identified eighteen proteins whose expression levels changed more than twofold as compared to normal controls. In particular, we found that PRDX1 expression in culture medium was elevated by a lipopolysaccharide (LPS challenge in airway epithelial cells in vitro. Furthermore, overexpression of PRDX1 increased the expression of proinflammatory cytokines interleukin-6 (IL-6, interleukin-8 (IL-8, and tumor necrosis factor-α (TNF-α, whereas knockdown of PRDX1 led to downregulated expression of cytokines induced by LPS. In conclusion, our findings provide a global alteration in the proteome of lung tissues in the ALI rat model and indicate that PRDX1 may play a critical role in the pathogenesis of ARDS by promoting inflammation and represent a novel strategy for the development of new therapies against ALI.

  10. Microevolution of Pseudomonas aeruginosa to a chronic pathogen of the cystic fibrosis lung.

    Science.gov (United States)

    Hogardt, Michael; Heesemann, Jürgen

    2013-01-01

    Pseudomonas aeruginosa is the leading pathogen of chronic cystic fibrosis (CF) lung infection. Life-long persistance of P. aeruginosa in the CF lung requires a sophisticated habitat-specific adaptation of this pathogen to the heterogeneous and fluctuating lung environment. Due to the high selective pressure of inflamed CF lungs, P. aeruginosa increasingly experiences complex physiological and morphological changes. Pulmonary adaptation of P. aeruginosa is mediated by genetic variations that are fixed by the repeating interplay of mutation and selection. In this context, the emergence of hypermutable phenotypes (mutator strains) obviously improves the microevolution of P. aeruginosa to the diverse microenvironments of the CF lung. Mutator phenotypes are amplified during CF lung disease and accelerate the intraclonal diversification of P. aeruginosa. The resulting generation of numerous subclonal variants is advantegous to prepare P. aeruginosa population for unpredictable stresses (insurance hypothesis) and thus supports long-term survival of this pathogen. Oxygen restriction within CF lung environment further promotes persistence of P. aeruginosa due to increased antibiotic tolerance, alginate production and biofilm formation. Finally, P. aeruginosa shifts from an acute virulent pathogen of early infection to a host-adapted chronic virulent pathogen of end-stage infection of the CF lung. Common changes that are observed among chronic P. aeruginosa CF isolates include alterations in surface antigens, loss of virulence-associated traits, increasing antibiotic resistances, the overproduction of the exopolysaccharide alginate and the modulation of intermediary and micro-aerobic metabolic pathways (Hogardt and Heesemann, Int J Med Microbiol 300(8):557-562, 2010). Loss-of-function mutations in mucA and lasR genes determine the transition to mucoidity and loss of quorum sensing, which are hallmarks of the chronic virulence potential of P. aeruginosa. Metabolic factors

  11. Large Porous Particles for Sustained Release of a Decoy Oligonucelotide and Poly(ethylenimine): Potential for Combined Therapy of Chronic Pseudomonas aeruginosa Lung Infections.

    Science.gov (United States)

    d'Angelo, Ivana; Perfetto, Brunella; Costabile, Gabriella; Ambrosini, Veronica; Caputo, Pina; Miro, Agnese; d'Emmanuele di Villa Bianca, Roberta; Sorrentino, Raffaella; Donnarumma, Giovanna; Quaglia, Fabiana; Ungaro, Francesca

    2016-05-01

    We have recently demonstrated that the specific inhibition of nuclear factor-κB by a decoy oligonucleotide (dec-ODN) delivered through inhalable large porous particles (LPP) made of poly(lactic-co-glycolic acid) (PLGA) may be highly beneficial for long-term treatment of lung inflammation. Nevertheless, besides chronic inflammation, multifunctional systems aimed to control also infection are required in chronic lung diseases, such as cystic fibrosis (CF). In this work, we tested the hypothesis that engineering PLGA-based LPP with branched poly(ethylenimine) (PEI) may improve LPP properties for pulmonary delivery of dec-ODN, with particular regard to the treatment of Pseudomonas aeruginosa lung infections. After getting insight into the role of PEI on the technological properties of PLGA-based LPP for delivery of dec-ODN, the putative synergistic effect of PEI free or PEI released from LPP on in vitro antimicrobial activity of tobramycin (Tb) and aztreonam (AZT) against P. aeruginosa was elucidated. Meanwhile, cytotoxicity studies on A549 cells were carried out. Results clearly demonstrate that the dry powders have promising aerosolization properties and afford a prolonged in vitro release of both dec-ODN and PEI. The encapsulation of PEI into LPP results in a 2-fold reduction of the minimum inhibitory concentration of AZT, while reducing the cytotoxic effect of PEI. Of note, the developed ODN/PLGA/PEI LPP persisted at lung at least for 14 days after intratracheal administration in rats where they can provide sustained and combined release of dec-ODN and PEI. dec-ODN will likely act as an anti-inflammatory drug, while PEI may enhance the therapeutic activity of inhaled antibiotics, which are commonly employed for the treatment of concomitant lung infections. PMID:27002689

  12. Novel mouse model of chronic Pseudomonas aeruginosa lung infection mimicking cystic fibrosis

    DEFF Research Database (Denmark)

    Hoffmann, Nadine; Rasmussen, Thomas Bovbjerg; Jensen, Peter Østrup;

    2005-01-01

    Pseudomonas aeruginosa causes a chronic infection in the lungs of cystic fibrosis (CF) patients by establishing an alginate-containing biofilm. The infection has been studied in several animal models; however, most of the models required artificial embedding of the bacteria. We present here a new...... pulmonary mouse model without artificial embedding. The model is based on a stable mucoid CF sputum isolate (NH57388A) with hyperproduction of alginate due to a deletion in mucA and functional N-acylhomoserine lactone (AHL)-based quorum-sensing systems. Chronic lung infection could be established in both CF...

  13. The relation of hepcidin to iron disorders, inflammation and hemoglobin in chronic kidney disease.

    Directory of Open Access Journals (Sweden)

    Lucile Mercadal

    Full Text Available The metabolism of hepcidin is profoundly modified in chronic kidney disease (CKD. We investigated its relation to iron disorders, inflammation and hemoglobin (Hb level in 199 non-dialyzed, non-transplanted patients with CKD stages 1-5. All had their glomerular filtration rate measured by 51Cr-EDTA renal clearance (mGFR, as well as measurements of iron markers including hepcidin and of erythropoietin (EPO. Hepcidin varied from 0.2 to 193 ng/mL. The median increased from 23.3 ng/mL [8.8-28.7] to 36.1 ng/mL [14.1-92.3] when mGFR decreased from ≥60 to <15 mL/min/1.73 m2 (p = 0.02. Patients with absolute iron deficiency (transferrin saturation (TSAT <20% and ferritin <40 ng/mL had the lowest hepcidin levels (5.0 ng/mL [0.7-11.7], and those with a normal iron profile (TSAT ≥20% and ferritin ≥40, the highest (34.5 ng/mL [23.7-51.6]. In multivariate analysis, absolute iron deficiency was associated with lower hepcidin values, and inflammation combined with a normal or functional iron profile with higher values, independent of other determinants of hepcidin concentration, including EPO, mGFR, and albuminemia. The hepcidin level, although it rose overall when mGFR declined, collapsed in patients with absolute iron deficiency. There was a significant interaction with iron status in the association between Hb and hepcidin. Except in absolute iron deficiency, hepcidin's negative association with Hb level indicates that it is not down-regulated in CKD anemia.

  14. Treatment of lung infection in patients with cystic fibrosis

    DEFF Research Database (Denmark)

    Döring, Gerd; Flume, Patrick; Heijerman, Harry;

    2012-01-01

    In patients with cystic fibrosis (CF) lung damage secondary to chronic infection is the main cause of death. Treatment of lung disease to reduce the impact of infection, inflammation and subsequent lung injury is therefore of major importance. Here we discuss the present status of antibiotic...

  15. Inhaled unfractionated heparin improves abnormalities of alveolar coagulation, fibrinolysis and inflammation in endotoxemia-induced lung injury rats

    Institute of Scientific and Technical Information of China (English)

    WANG Zong-yu; WU Sheng-nan; ZHU Zhao-zhong; YANG Ba-xian; ZHU Xi

    2013-01-01

    Background Acute lung injury/acute respiratory distress syndrome presents with not only local inflammation,but also pulmonary coagulopathy which is characterized by an alveolar procoagulant response,anticoagulant inhibition,fibrinolytic supression and fibrin deposition.We thus had hypothesized that if aerosolized unfractionated heparin was inhaled into alveolar spaces,it could block the procoagulant tendency,lessen depletion of coagulation factors,and even influence the inflammatory response.We also assessed the effects of different administration regimens of heparin.Methods Male Wistar rats were given inhaled heparin starting 30 minutes before (prophylactic heparin) or 2 hours after (therapeutic heparin) intravenous lipopolysaccharide (LPS) was administered at 6-hour intervals; control groups received inhaled normal saline with or without being exposed to LPS.Thrombin-antithrombin complexes,activated protein C,tissue type and urokinase type plasminogen activators (t-PNu-PA),plasminogen activator inhibitor-1 (PAl-1),tumor necrosis factor-α,interleukin-6 in bronchoalveolar lavage,and lung tissue myeloperoxidase activity,and histology score were measured at three time-points.PAI-1/(t-PA + u-PA) was calculated based on the before-mentioned parameters.Statistical analysis was made using one-way analysis of variance (ANOVA) with post hoc test or Student's t test in the case of heterogeneity of variance.Results An alveolar procoagulant reaction,depressed fibrinolysis,and inflammatory response occurred in endotoxemia-induced lung injury.Local prophylactic application of heparin attenuated coagulation and early inflammation,promoted fibrinolysis,and reduced the histology score.Therapeutic application of heparin had similar,but weaker effects.Conclusions Intrapulmonary application of unfractionated heparin by inhalation might inhibit alveolar procoagulant reaction and the early inflammatory response,promote flbrinolysis,and alleviate pulmonary pathology in endotoxemia

  16. Chronic cadmium exposure in vitro induces cancer cell characteristics in human lung cells

    Energy Technology Data Exchange (ETDEWEB)

    Person, Rachel J.; Tokar, Erik J.; Xu, Yuanyuan; Orihuela, Ruben; Ngalame, Ntube N. Olive; Waalkes, Michael P., E-mail: waalkes@niehs.nih.gov

    2013-12-01

    Cadmium is a known human lung carcinogen. Here, we attempt to develop an in vitro model of cadmium-induced human lung carcinogenesis by chronically exposing the peripheral lung epithelia cell line, HPL-1D, to a low level of cadmium. Cells were chronically exposed to 5 μM cadmium, a noncytotoxic level, and monitored for acquired cancer characteristics. By 20 weeks of continuous cadmium exposure, these chronic cadmium treated lung (CCT-LC) cells showed marked increases in secreted MMP-2 activity (3.5-fold), invasion (3.4-fold), and colony formation in soft agar (2-fold). CCT-LC cells were hyperproliferative, grew well in serum-free media, and overexpressed cyclin D1. The CCT-LC cells also showed decreased expression of the tumor suppressor genes p16 and SLC38A3 at the protein levels. Also consistent with an acquired cancer cell phenotype, CCT-LC cells showed increased expression of the oncoproteins K-RAS and N-RAS as well as the epithelial-to-mesenchymal transition marker protein Vimentin. Metallothionein (MT) expression is increased by cadmium, and is typically overexpressed in human lung cancers. The major MT isoforms, MT-1A and MT-2A were elevated in CCT-LC cells. Oxidant adaptive response genes HO-1 and HIF-1A were also activated in CCT-LC cells. Expression of the metal transport genes ZNT-1, ZNT-5, and ZIP-8 increased in CCT-LC cells culminating in reduced cadmium accumulation, suggesting adaptation to the metal. Overall, these data suggest that exposure of human lung epithelial cells to cadmium causes acquisition of cancer cell characteristics. Furthermore, transformation occurs despite the cell's ability to adapt to chronic cadmium exposure. - Highlights: • Chronic cadmium exposure induces cancer cell characteristics in human lung cells. • This provides an in vitro model of cadmium-induced human lung cell transformation. • This occurred with general and lung specific changes typical for cancer cells. • These findings add insight to the

  17. Chronic cadmium exposure in vitro induces cancer cell characteristics in human lung cells

    International Nuclear Information System (INIS)

    Cadmium is a known human lung carcinogen. Here, we attempt to develop an in vitro model of cadmium-induced human lung carcinogenesis by chronically exposing the peripheral lung epithelia cell line, HPL-1D, to a low level of cadmium. Cells were chronically exposed to 5 μM cadmium, a noncytotoxic level, and monitored for acquired cancer characteristics. By 20 weeks of continuous cadmium exposure, these chronic cadmium treated lung (CCT-LC) cells showed marked increases in secreted MMP-2 activity (3.5-fold), invasion (3.4-fold), and colony formation in soft agar (2-fold). CCT-LC cells were hyperproliferative, grew well in serum-free media, and overexpressed cyclin D1. The CCT-LC cells also showed decreased expression of the tumor suppressor genes p16 and SLC38A3 at the protein levels. Also consistent with an acquired cancer cell phenotype, CCT-LC cells showed increased expression of the oncoproteins K-RAS and N-RAS as well as the epithelial-to-mesenchymal transition marker protein Vimentin. Metallothionein (MT) expression is increased by cadmium, and is typically overexpressed in human lung cancers. The major MT isoforms, MT-1A and MT-2A were elevated in CCT-LC cells. Oxidant adaptive response genes HO-1 and HIF-1A were also activated in CCT-LC cells. Expression of the metal transport genes ZNT-1, ZNT-5, and ZIP-8 increased in CCT-LC cells culminating in reduced cadmium accumulation, suggesting adaptation to the metal. Overall, these data suggest that exposure of human lung epithelial cells to cadmium causes acquisition of cancer cell characteristics. Furthermore, transformation occurs despite the cell's ability to adapt to chronic cadmium exposure. - Highlights: • Chronic cadmium exposure induces cancer cell characteristics in human lung cells. • This provides an in vitro model of cadmium-induced human lung cell transformation. • This occurred with general and lung specific changes typical for cancer cells. • These findings add insight to the relationship

  18. Interleukin-33 from Monocytes Recruited to the Lung Contributes to House Dust Mite-Induced Airway Inflammation in a Mouse Model

    Science.gov (United States)

    Tashiro, Hiroki; Takahashi, Koichiro; Hayashi, Shinichiro; Kato, Go; Kurata, Keigo; Kimura, Shinya; Sueoka-Aragane, Naoko

    2016-01-01

    Background Interleukin-33 (IL-33) activates group 2 innate lymphoid cells (ILC2), resulting in T-helper-2 inflammation in bronchial asthma. Airway epithelial cells were reported as sources of IL-33 during apoptosis and necrosis. However, IL-33 is known to be from sources other than airway epithelial cells such as leukocytes, and the mechanisms of IL-33 production and release are not fully understood. The aim of this study was to clarify the role of IL-33 production by monocytes in airway inflammation. Methods BALB/c mice were sensitized and challenged with a house dust mite (HDM) preparation. Airway inflammation was assessed by quantifying inflammatory cells in bronchoalveolar lavage (BAL) fluid, and IL-25, IL-33, and thymic stromal lymphopoietin (TSLP) levels in lung. Immunohistochemistry for IL-33 in lung sections was also performed. Ly6c, CD11b, and CD11c expression was examined by flow cytometry. Clodronate liposomes were used in the HDM-airway inflammation model to deplete circulating monocytes. Results The IL-33, but not IL-25 or TSLP, level in lung homogenates was markedly increased in HDM mice compared to control mice. IL-33-positive cells in the lungs were identified using immunohistochemistry and were increased in areas surrounding bronchi and vasculature. Furthermore, IL-33 levels were increased in mononuclear cells derived from lungs of HDM mice compared to controls. The expression of Ly6c in mononuclear cells was significantly higher in HDM mice than in controls. Treatment with clodronate liposomes led to inhibition of not only inflammatory cells in BAL fluid, airway hyper reactivity and Th2 cytokines in lung, but also IL-33 in lung. Conclusion IL-33 from monocytes recruited to the lung may contribute to the pathogenesis of HDM-induced airway inflammation. PMID:27310495

  19. Interleukin-33 from Monocytes Recruited to the Lung Contributes to House Dust Mite-Induced Airway Inflammation in a Mouse Model.

    Directory of Open Access Journals (Sweden)

    Hiroki Tashiro

    Full Text Available Interleukin-33 (IL-33 activates group 2 innate lymphoid cells (ILC2, resulting in T-helper-2 inflammation in bronchial asthma. Airway epithelial cells were reported as sources of IL-33 during apoptosis and necrosis. However, IL-33 is known to be from sources other than airway epithelial cells such as leukocytes, and the mechanisms of IL-33 production and release are not fully understood. The aim of this study was to clarify the role of IL-33 production by monocytes in airway inflammation.BALB/c mice were sensitized and challenged with a house dust mite (HDM preparation. Airway inflammation was assessed by quantifying inflammatory cells in bronchoalveolar lavage (BAL fluid, and IL-25, IL-33, and thymic stromal lymphopoietin (TSLP levels in lung. Immunohistochemistry for IL-33 in lung sections was also performed. Ly6c, CD11b, and CD11c expression was examined by flow cytometry. Clodronate liposomes were used in the HDM-airway inflammation model to deplete circulating monocytes.The IL-33, but not IL-25 or TSLP, level in lung homogenates was markedly increased in HDM mice compared to control mice. IL-33-positive cells in the lungs were identified using immunohistochemistry and were increased in areas surrounding bronchi and vasculature. Furthermore, IL-33 levels were increased in mononuclear cells derived from lungs of HDM mice compared to controls. The expression of Ly6c in mononuclear cells was significantly higher in HDM mice than in controls. Treatment with clodronate liposomes led to inhibition of not only inflammatory cells in BAL fluid, airway hyper reactivity and Th2 cytokines in lung, but also IL-33 in lung.IL-33 from monocytes recruited to the lung may contribute to the pathogenesis of HDM-induced airway inflammation.

  20. Development and validation of an animal model of prostate inflammation-induced chronic pelvic pain: evaluating from inflammation of the prostate to pain behavioral modifications.

    Directory of Open Access Journals (Sweden)

    Feng Zeng

    Full Text Available BACKGROUND: Chronic prostatitis/Chronic pelvic pain syndrome (CP/CPPS is the most common type of prostatitis. Due to the lack of a suitable animal model partly, the pathogenesis for this condition is obscure. In the current study we developed and validated an animal model for nonbacterial prostatitis and prostate inflammation-induced chronic pelvic pain in rats with the use of intraprostatic injection of λ-carrageenan. METHODS: Male Sprague-Dawley rats weighing 250-350 g were used for the experiments. After intraprostatic injection of 3% λ-carrageenan, at different time points(after 24 h, 7 d, 14 d and 30 d of injection, radiant heat and von Frey filaments were applied to the scrotum of rats to measure the heat and mechanical thresholds respectively. Then the prostate was removed for histology, and cyclooxygenase (COX 2 protein expression was determined by Western-blot. Evans blue(50 mg/kg was also injected intravenously to assess for plasma protein extravasation at different time points after injection of λ-carrageenan. RESULTS: Compared to control group, inflamed animals showed a significant reduction in mechanical threshold (mechanical allodynia at 24 h and 7d(p = 0.022,0.046, respectively, and a significant reduction in heat threshold (thermal hyperalgesia at 24 h, 7d and 14 d(p = 0.014, 0.018, 0.002, respectively in the scrotal skin. Significant increase of inflammatory cell accumulation, COX2 expression and Evans blue extravasation were observed at 24 h, 7d and 14 d after injection. CONCLUSIONS: Intraprostatic λ-carrageenan injection induced neurogenic prostatitis and prostate inflammation pain, which lasted at least 2 weeks. The current model is expected to be a valuable preclinical tool to study the neurobiological mechanisms of male chronic pelvic pain.

  1. Pulmonary carcinogenesis and chronic beta irradiation of lung

    International Nuclear Information System (INIS)

    Light water nuclear power reactor fuel cycles at various stages contain substantial quantities of β-emitting radionuclides. Thus, in the event of an accident, there is potential for inhalation exposure of man to various types and forms of β-emitting radionuclides. In order to study the biological effects of such potential exposures, a series of life span studies have been initiated in which beagle dogs have been exposed to inhalation to achieve graded lung burdens of a relatively insoluble fused clay form of β-emitting radionuclides. The specific radionuclides, 90Y, 91Y, 144Ce, or 90Sr, were selected on the basis of physical half-life to produce a variety of radiation-dose patterns to the lung. Early effects have been the development of radiation pneumonitis and progressive pulmonary fibrosis. In general, dogs which receive high- and rapidly-declining dose-rate exposure from 90Y or 91Y die earlier and at lower cumulative doses than dogs exposed to 144Ce or 90Sr. By contrast, the incidence of later-occurring malignant lung tumors and the degree of inflammatory response is greater in dogs which received protracted low dose-rate exposure associated with 144Ce and 90Sr. Of particular note is the nature of the lung tumors thus far observed

  2. Nebulized Anticoagulants Limit Pulmonary Coagulopathy, But Not Inflammation, in a Model of Experimental Lung Injury

    NARCIS (Netherlands)

    J.J. Hofstra; A.P. Vlaar; A.D. Cornet; B. Dixon; J.J. Roelofs; G. Choi; T. van der Poll; M. Levi; M.J. Schultz

    2010-01-01

    Background: Pulmonary coagulopathy may contribute to an adverse outcome in lung injury. We assessed the effects of local anticoagulant therapy on bronchoalveolar and systemic haemostasis in a rat model of endotoxemia-induced lung injury. Methods: Male Sprague-Dawley rats were intravenously challenge

  3. Nebulized anticoagulants limit pulmonary coagulopathy, but not inflammation, in a model of experimental lung injury

    NARCIS (Netherlands)

    Hofstra, Jorrit J; Vlaar, Alexander P; Cornet, Alexander D; Dixon, Barry; Roelofs, Joris J; Choi, Goda; van der Poll, Tom; Levi, Marcel; Schultz, Marcus J

    2010-01-01

    BACKGROUND: Pulmonary coagulopathy may contribute to an adverse outcome in lung injury. We assessed the effects of local anticoagulant therapy on bronchoalveolar and systemic haemostasis in a rat model of endotoxemia-induced lung injury. METHODS: Male Sprague-Dawley rats were intravenously challenge

  4. Microbiota alterations in acute and chronic gastrointestinal inflammation of cats and dogs.

    Science.gov (United States)

    Honneffer, Julia B; Minamoto, Yasushi; Suchodolski, Jan S

    2014-11-28

    The intestinal microbiota is the collection of the living microorganisms (bacteria, fungi, protozoa, and viruses) inhabiting the gastrointestinal tract. Novel bacterial identification approaches have revealed that the gastrointestinal microbiota of dogs and cats is, similarly to humans, a highly complex ecosystem. Studies in dogs and cats have demonstrated that acute and chronic gastrointestinal diseases, including inflammatory bowel disease (IBD), are associated with alterations in the small intestinal and fecal microbial communities. Of interest is that these alterations are generally similar to the dysbiosis observed in humans with IBD or animal models of intestinal inflammation, suggesting that microbial responses to inflammatory conditions of the gut are conserved across mammalian host types. Studies have also revealed possible underlying susceptibilities in the innate immune system of dogs and cats with IBD, which further demonstrate the intricate relationship between gut microbiota and host health. Commonly identified microbiome changes in IBD are decreases in bacterial groups within the phyla Firmicutes and Bacteroidetes, and increases within Proteobacteia. Furthermore, a reduction in the diversity of Clostridium clusters XIVa and IV (i.e., Lachnospiraceae and Clostridium coccoides subgroups) are associated with IBD, suggesting that these bacterial groups may play an important role in maintenance of gastrointestinal health. Future studies are warranted to evaluate the functional changes associated with intestinal dysbiosis in dogs and cats.

  5. The association between obesity and fluid intelligence impairment is mediated by chronic low-grade inflammation.

    Science.gov (United States)

    Spyridaki, Eirini C; Simos, Panagiotis; Avgoustinaki, Pavlina D; Dermitzaki, Eirini; Venihaki, Maria; Bardos, Achilles N; Margioris, Andrew N

    2014-11-28

    Published evidence suggests that obesity impairs cognition. Development of chronic low-grade inflammation (CLGI) represents the earliest consequence of obesity. The present study investigated the association between obesity and fluid intelligence impairment and assessed the potential mediating role of CLGI and psychological (depression/anxiety symptoms), lifestyle (exercise) and physiological (metabolic dysfunction indices) factors in this association. Clinically healthy participants (n 188), grouped as per BMI, underwent cognitive (General Ability Measure for Adults), psychological (Beck Depression Inventory-II and State-Trait Anxiety Inventory) and activity (Godin leisure-time physical activity) measurements. Biochemical parameters included the following: (a) indices of CLGI (high-sensitivity C-reactive protein, erythrocyte sedimentation rate and fibrinogen); (b) insulin resistance (Homeostasis Model Assessment of Insulin Resistance index); (c) adiposity (plasma adiponectin). An inverse association between elevated BMI and fluid intelligence was observed, with obese participants displaying significantly poorer performance compared with age-matched normal-weight peers. Structural equation modelling results were consistent with a negative impact of obesity on cognition that was mediated by CLGI. The results of the present study support the hypothesis that reduced general cognitive ability is associated with obesity, an adverse effect mainly mediated by obesity-associated activation of innate immunity.

  6. Immune dysregulation mediated by the oral microbiome: potential link to chronic inflammation and atherosclerosis.

    Science.gov (United States)

    Slocum, C; Kramer, C; Genco, C A

    2016-07-01

    Cardiovascular disease is an inflammatory disorder characterized by the progressive formation of plaque in coronary arteries, termed atherosclerosis. It is a multifactorial disease that is one of the leading causes of death worldwide. Although a number of risk factors have been associated with disease progression, the underlying inflammatory mechanisms contributing to atherosclerosis remain to be fully delineated. Within the last decade, the potential role for infection in inflammatory plaque progression has received considerable interest. Microbial pathogens associated with periodontal disease have been of particular interest due to the high levels of bacteremia that are observed after routine dental procedures and every day oral activities, such as tooth brushing. Here, we explore the potential mechanisms that may explain how periodontal pathogens either directly or indirectly elicit immune dysregulation and consequently progressive inflammation manifested as atherosclerosis. Periodontal pathogens have been shown to contribute directly to atherosclerosis by disrupting endothelial cell function, one of the earliest indicators of cardiovascular disease. Oral infection is thought to indirectly induce elevated production of inflammatory mediators in the systemic circulation. Recently, a number of studies have been conducted focusing on how disruption of the gut microbiome influences the systemic production of proinflammatory cytokines and consequently exacerbation of inflammatory diseases such as atherosclerosis. It is clear that the immune mechanisms leading to atherosclerotic plaque progression, by oral infection, are complex. Understanding the immune pathways leading to disease progression is essential for the future development of anti-inflammatory therapies for this chronic disease. PMID:26791914

  7. New Insights on COX-2 in Chronic Inflammation Driving Breast Cancer Growth and Metastasis.

    Science.gov (United States)

    Hugo, Honor J; Saunders, C; Ramsay, R G; Thompson, E W

    2015-12-01

    The medicinal use of aspirin stretches back to ancient times, before it was manufactured in its pure form in the late 19th century. Its accepted mechanistic target, cyclooxygenase (COX), was discovered in the 1970s and since this landmark discovery, the therapeutic application of aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) has increased dramatically. The most significant benefits of NSAIDs are in conditions involving chronic inflammation (CI). Given the recognized role of CI in cancer development, the use of long-term NSAID treatment in the prevention of cancer is an enticing possibility. COX-2 is a key driver of CI, and here we review COX-2 expression as a predictor of survival in various cancer types, including breast. Obesity and post-partum involution are natural inflammatory states that are associated with increased breast cancer risk. We outline the COX-2 mediated mechanisms contributing to the growth of cancers. We dissect the cellular mechanism of epithelial-mesenchymal transition (EMT) and how COX-2 may induce this to facilitate tumor progression. Finally we examine the potential regulation of COX-2 by c-Myb, and the possible interplay between c-Myb/COX-2 in proliferation, and hypoxia inducible factor-1 alpha (HIF1α)/COX-2 in invasive pathways in breast cancer.

  8. Bronchial brush biopsies for studies of epithelial inflammation in stable asthma and nonobstructive chronic bronchitis.

    Science.gov (United States)

    Riise, G C; Andersson, B; Ahlstedt, S; Enander, I; Söderberg, M; Löwhagen, O; Larsson, S

    1996-08-01

    Recently, bronchial brush biopsy (BBB) has been introduced as a complimentary method to bronchial forceps biopsy for the study of bronchial epithelial cells. We wanted to determine whether epithelial inflammatory cells in bronchial brush biopsies can reflect mucosal inflammation assessed indirectly by levels of cellular activation markers in bronchial lavage fluid. We studied 15 healthy controls, 11 asthmatics with regular steroid inhalation therapy, 13 asthmatics without steroids, and 10 smokers with nonobstructive chronic bronchitis. Differential counts of epithelial and inflammatory cells were made from the BBB material. Bronchial lavage levels of eosinophil cationic protein (ECP), myeloperoxidase (MPO), tryptase, hyaluronan and interleukin-8 (IL-8) were measured as indirect markers for inflammatory cell activation. We found an increased percentage of eosinophil granulocytes in the BBB from the steroid-untreated asthmatic patients (1.16%) in comparison to the other groups (0.11%, 0.09% and 0.02%, respectively; pairways disease. These changes appear to relate to the degree of inflammatory activity and disease severity in asthma. PMID:8866592

  9. Hyperglycemia Aggravates Hepatic Ischemia Reperfusion Injury by Inducing Chronic Oxidative Stress and Inflammation

    Directory of Open Access Journals (Sweden)

    Yihan Zhang

    2016-01-01

    Full Text Available Aim. To investigate whether hyperglycemia will aggravate hepatic ischemia reperfusion injury (HIRI and the underlying mechanisms. Methods. Control and streptozotocin-induced diabetic Sprague-Dawley rats were subjected to partial hepatic ischemia reperfusion. Liver histology, transferase, inflammatory cytokines, and oxidative stress were assessed accordingly. Similarly, BRL-3A hepatocytes were subjected to hypoxia/reoxygenation (H/R after high (25 mM or low (5.5 mM glucose culture. Cell viability, reactive oxygen species (ROS, and activation of nuclear factor-erythroid 2-related factor 2 (Nrf2 and nuclear factor of kappa light polypeptide gene enhancer in B-cells (NF-κB were determined. Results. Compared with control, diabetic rats presented more severe hepatic injury and increased hepatic inflammatory cytokines and oxidative stress. HIRI in diabetic rats could be ameliorated by pretreatment of N-acetyl-L-cysteine (NAC or apocynin. Excessive ROS generation and consequent Nrf2 and NF-κB translocation were determined after high glucose exposure. NF-κB translocation and its downstream cytokines were further increased in high glucose cultured group after H/R. While proper regulation of Nrf2 to its downstream antioxidases was observed in low glucose cultured group, no further induction of Nrf2 pathway by H/R after high glucose culture was identified. Conclusion. Hyperglycemia aggravates HIRI, which might be attributed to chronic oxidative stress and inflammation and potential malfunction of antioxidative system.

  10. Intravesical Dimethyl Sulfoxide Inhibits Acute and Chronic Bladder Inflammation in Transgenic Experimental Autoimmune Cystitis Models

    Directory of Open Access Journals (Sweden)

    Ronald Kim

    2011-01-01

    Full Text Available New animal models are greatly needed in interstitial cystitis/painful bladder syndrome (IC/PBS research. We recently developed a novel transgenic cystitis model (URO-OVA mice that mimics certain key aspects of IC/PBS pathophysiology. This paper aimed to determine whether URO-OVA cystitis model was responsive to intravesical dimethyl sulfoxide (DMSO and if so identify the mechanisms of DMSO action. URO-OVA mice developed acute cystitis upon adoptive transfer of OVA-specific OT-I splenocytes. Compared to PBS-treated bladders, the bladders treated with 50% DMSO exhibited markedly reduced bladder histopathology and expression of various inflammatory factor mRNAs. Intravesical DMSO treatment also effectively inhibited bladder inflammation in a spontaneous chronic cystitis model (URO-OVA/OT-I mice. Studies further revealed that DMSO could impair effector T cells in a dose-dependent manner in vitro. Taken together, our results suggest that intravesical DMSO improves the bladder histopathology of IC/PBS patients because of its ability to interfere with multiple inflammatory and bladder cell types.

  11. Chronic infection with Helicobacter pylori does not provoke major systemic inflammation in healthy adults

    DEFF Research Database (Denmark)

    Brenner, H; Berg, Gabriele; Fröhlich, M;

    1999-01-01

    It has been suggested that chronic infection with Helicobacter pylori (H. pylori), in particular infection with virulent strains producing the cytotoxin-associated protein CagA, may increase the risk of coronary heart disease by generation of a persistent low-grade inflammatory stimulus. We...... assessed the relation between serological markers of H. pylori infection and various markers of systemic inflammation in a population-based sample of 1834 men and women aged 18-88. A total of 39.3% of the sample had a positive IgG response, and among these a slight majority was CagA positive. Infection...... with H. pylori was unrelated to C-reactive protein and the leukocyte count, regardless of CagA status. There was an inverse relation between H. pylori infection and serum albumin. The adjusted OR (95% CI) of an albumin level in the bottom versus the top third were 2.2 (1.5-3.1) and 2.0 (1...

  12. Ascorbic acid: its role in immune system and chronic inflammation diseases.

    Science.gov (United States)

    Sorice, Angela; Guerriero, Eliana; Capone, Francesca; Colonna, Giovanni; Castello, Giuseppe; Costantini, Susan

    2014-05-01

    Ascorbic acid (AA), also known as vitamin C, was initially identified as the factor preventing the scurvy disease, and became very popular for its antioxidant properties. It is an important co-substrate of a large class of enzymes, and regulates gene expression by interacting with important transcription factors. AA is important in all stressful conditions that are linked to inflammatory processes and involve immunity. It has been known for decades that the persistence of an inflammatory stimulus is responsible for the onset of many diseases. AA is essential to stimulate the immune system by increasing the strength and protection of the organism. Therefore, its immunostimulant, antinflammatory, antiviral and antibacterial roles are well known, we have summarized its main functions in different types of diseases related to the immune system and chronic inflammation. We can conclude that AA, due to its effects and diversity of regulated pathways, is suitable for use in various fields of medicine including immunology, toxicology, radiobiology and others. AA is not preferable to be used as an isolated mode of treatment, but it can be co-applied as an adjuvant to regulate immunity, gene expression and other important physiological processes. However, we propose that future studies will take into consideration the research of new combinations of antioxidant natural substances and drugs. PMID:24766384

  13. Chronic low-grade inflammation, lipid risk factors and mortality in functionally dependent elderly

    Directory of Open Access Journals (Sweden)

    Vasović Olga

    2010-01-01

    Full Text Available Background/Aim. It has been proved that a highly sensitive C-reactive protein (hsCRP can be used as an established marker of chronic inflammation for cardiovascular risk assessment. Since mean values of both low-density cholesterol (LDL-C and high-density lipoprotein cholesterol (HDL-C decrease during aging, the knowledge that increased hsCRP concentration predicts mortality (Mt would influence therapy and treatment outcome. The aim of this study was to examine importance of chronic low grade inflammation and its association with lipid risk factors for all-cause Mt in functionally dependent elderly. Methods. The participants of this longitudinal prospective study were 257 functionally dependent elderly aged 65-99 years. Baseline measurements: anthropometric measurements, blood pressure, fasting plasma total cholesterol (TC, triglyceride (TG, HDL-C, LDL-C, non- HDL-C, hemoglobin A1c (HbA1c were recorded and different lipid ratios were calculated. Inflammation was assessed by the levels of white blood cells, fibrinogen and hsCRP. The participants with hsCRP grater than 10 mg/L were excluded from the study. The residual participants (77.4% women were divided into three groups according to their hsCRP levels: a low (< 1 mg/L, n = 70, average (1 to 3 mg/L, n = 69, and high (3-10 mg/L, n = 69 hsCRP group. Associations of all-cause Mt with different risk factors were examined using logistic regression analysis. Results. The hsCRP level showed a significant positive correlation with waist (r = 0.199, p = 0.004 and hip (r = 0.187, p = 0.007 circumferences, body mass index (r = 0.143, p = 0.040 and serum triglyceride level (r = 0.139, p = 0.045 and significant negative correlation with HDL-C (r = -0.164, p = 0.018. Ratios TC/HDL-C and TG/HDL-C were significantly smaller in the low hsCRP group compared to the average hsCRP group (p = 0.019, p = 0.045, respectively and without significant differences compared with the high hsCRP group. Two years after the

  14. Uncontrolled airway inflammation in lung disease represents a defect in counter-regulatory signaling

    OpenAIRE

    Planaguma, Anna; Levy, Bruce D.

    2008-01-01

    Counter-regulatory lipid mediators are generated during airway inflammation to promote resolution. Defects in the production of these lipid mediators have now been associated with several diseases of persistent airway inflammation. Lipoxins are the lead members of this class of anti-inflammatory and proresolving chemical mediators. Recently, several new families of fatty acid-derived counter-regulatory mediators have been discovered, including the resolvins and protectins. Diminished formatio...

  15. Metabolically induced liver inflammation leads to NASH and differs from LPS- or IL-1 beta-induced chronic inflammation

    NARCIS (Netherlands)

    Liang, Wen; Lindeman, Jan H.; Menke, Aswin L.; Koonen, Debby P.; Morrison, Martine; Havekes, Louis M.; van den Hoek, Anita M.; Kleemann, Robert

    2014-01-01

    The nature of the chronic inflammatory component that drives the development of non-alcoholic steatohepatitis (NASH) is unclear and possible inflammatory triggers have not been investigated systematically. We examined the effect of non-metabolic triggers (lipopolysaccharide (LPS), interleukin-1 beta

  16. Pseudomonas aeruginosa mutations in lasl and rhll quorum sensing systems result in milder chronic lung infection

    DEFF Research Database (Denmark)

    Wu, H.; Song, Z.J.; Givskov, Michael Christian;

    2001-01-01

    To understand the importance of quorum sensing in chronic Pseudomonas aeruginosa lung infection, the in vivo pathogenic effects of the wild-type P aeruginosa PAO1 and its double mutant, PAO1 lasI rhlI, in which the signal-generating parts of the quorum sensing systems are defective were compared...

  17. Anti-proline-glycine-proline or antielastin autoantibodies are not evident in chronic inflammatory lung disease.

    LENUS (Irish Health Repository)

    Greene, Catherine M

    2010-01-01

    In patients with chronic inflammatory lung disease, pulmonary proteases can generate neoantigens from elastin and collagen with the potential to fuel autoreactive immune responses. Antielastin peptide antibodies have been implicated in the pathogenesis of tobacco-smoke-induced emphysema. Collagen-derived peptides may also play a role.

  18. Lung functions at school age and chronic exposure to outdoor and indoor air pollution

    Energy Technology Data Exchange (ETDEWEB)

    Neuberger, M.; Kundi, M.; Wiesenberger, W. [Vienna Univ. (Austria). Dept. of Preventive Medicine

    1995-12-31

    Early signs of lung function impairment have been found correlated with annual concentrations of outdoor air pollutants and with passive smoking. To investigate the combined effects of both indicators of chronic exposure to air pollution pulmonary functions in all elementary and high school children of an Austrian town was examined for 5 years. (author)

  19. Former Smoking Is a Risk Factor for Chronic Kidney Disease After Lung Transplantation

    NARCIS (Netherlands)

    Hellemons, M. E.; Agarwal, P. K.; van der Bij, W.; Verschuuren, E. A. M.; Postmus, D.; Erasmus, M. E.; Navis, G. J.; Bakker, S. J. L.

    2011-01-01

    Chronic kidney disease (CKD) is a common complication after lung transplantation (LTx). Smoking is a risk factor for many diseases, including CKD. Smoking cessation for >6 months is required for LTx enlistment. However, the impact of smoking history on CKD development after LTx remains unclear. We i

  20. A Combined Use of Acupuncture,Moxibustion and Long Dan Xie Gan Tang for Treatment of 36 Cases of Chronic Pelvic Inflammation

    Institute of Scientific and Technical Information of China (English)

    金亚蓓

    2004-01-01

    Objective: To observe the therapeutic effect of acupuncture and moxibustion on chronic pelvic inflammation. Method: Thirty-six cases of chronic pelvic inflammation were treated with acupuncture,the Pathogenic Fire of the Liver) and medicinal cake moxibustion. Result: The treatment resulted in cure in 9 cases, obvious effect in 16 cases, effect in 7 cases and no effect in 4 cases. Conclusion:Acupuncture, moxibustion and the ancient recipe Long Dan Xie Gan Tang used together can enhance the therapeutic effects on chronic pelvic inflammation.

  1. Pseudomonas aeruginosa Evolutionary Adaptation and Diversification in Cystic Fibrosis Chronic Lung Infections.

    Science.gov (United States)

    Winstanley, Craig; O'Brien, Siobhan; Brockhurst, Michael A

    2016-05-01

    Pseudomonas aeruginosa populations undergo a characteristic evolutionary adaptation during chronic infection of the cystic fibrosis (CF) lung, including reduced production of virulence factors, transition to a biofilm-associated lifestyle, and evolution of high-level antibiotic resistance. Populations of P. aeruginosa in chronic CF lung infections typically exhibit high phenotypic diversity, including for clinically important traits such as antibiotic resistance and toxin production, and this diversity is dynamic over time, making accurate diagnosis and treatment challenging. Population genomics studies reveal extensive genetic diversity within patients, including for transmissible strains the coexistence of highly divergent lineages acquired by patient-to-patient transmission. The inherent spatial structure and spatial heterogeneity of selection in the CF lung appears to play a key role in driving P. aeruginosa diversification. PMID:26946977

  2. Reduction of neutrophilic lung inflammation by inhalation of the compatible solute ectoine: a randomized trial with elderly individuals

    Directory of Open Access Journals (Sweden)

    Unfried K

    2016-10-01

    Full Text Available Klaus Unfried,1,* Ursula Krämer,1,* Ulrich Sydlik,1 Andrea Autengruber,1 Andreas Bilstein,2 Sabine Stolz,1 Alessandra Marini,1 Tamara Schikowski,1 Stefanie Keymel,3 Jean Krutmann1 1IUF Leibniz Research Institute of Environmental Medicine, 2bitop AG, Witten, 3Department of Cardiology, Pneumology and Angiology, Medical Faculty, Heinrich-Heine-University, Düsseldorf, Germany *These authors contributed equally to this work Background: Compatible solutes are natural substances that are known to stabilize cellular functions. Preliminary ex vivo and in vivo studies demonstrated that the compatible solute ectoine restores natural apoptosis rates of lung neutrophils and contributes to the resolution of lung inflammation. Due to the low toxicity and known compatibility of the substance, an inhalative application as an intervention strategy for humans suffering from diseases caused by neutrophilic inflammation, like COPD, had been suggested. As a first approach to test the feasibility and efficacy of such a treatment, we performed a population-based randomized trial.Objective: The objective of the study was to test whether the daily inhalation of the registered ectoine-containing medical device (Ectoin® inhalation solution leads to a reduction of neutrophilic cells and interleukin-8 (IL-8 levels in the sputum of persons with mild symptoms of airway disease due to lifelong exposure to environmental air pollution.Methods: A double-blinded placebo-controlled trial was performed to study the efficacy and safety of an ectoine-containing therapeutic. Prior to and after both inhalation periods, lung function, inflammatory parameters in sputum, serum markers, and quality-of-life parameters were determined.Results: While the other outcomes revealed no significant effects, sputum parameters were changed by the intervention. Nitrogen oxides (nitrate and nitrite were significantly reduced after ectoine inhalation with a mean quotient of 0.65 (95% confidence

  3. Blockade of Wnt/β-Catenin Pathway Aggravated Silica-Induced Lung Inflammation through Tregs Regulation on Th Immune Responses

    Directory of Open Access Journals (Sweden)

    Wujing Dai

    2016-01-01

    Full Text Available CD4+ T cells play an important role in regulating silica-induced inflammation and fibrosis. Recent studies showed that Wnt/β-catenin pathway could modulate the function and the differentiation of CD4+ T cells. Therefore, Wnt/β-catenin pathway may participate in the development and progress of silicosis. To investigate the role of Wnt/β-catenin pathway, we used lentivirus expressing β-catenin shRNA to block the Wnt/β-catenin pathway by intratracheal instillation to the mice model of silicosis. Treatment of lentivirus could significantly aggravate the silica-induced lung inflammation and attenuated the fibrosis at the late stage. By analyzing CD4+ T cells, we found that blockade of Wnt/β-catenin pathway suppressed regulatory T cells (Tregs. Reciprocally, enhanced Th17 response was responsible for the further accumulation of neutrophils and production of proinflammatory cytokines. In addition, blockade of Wnt/β-catenin pathway delayed the Th1/Th2 polarization by inhibiting Tregs and Th2 response. These results indicated that Wnt/β-catenin pathway could regulate Tregs to modulate Th immune response, which finally altered the pathological character of silicosis. Our study suggested that Wnt/β-catenin pathway might be a potential target to treat the silica-induced inflammation and fibrosis.

  4. In vivo hydroquinone exposure alters circulating neutrophil activities and impairs LPS-induced lung inflammation in mice.

    Science.gov (United States)

    Ribeiro, André Luiz Teroso; Shimada, Ana Lúcia Borges; Hebeda, Cristina Bichels; de Oliveira, Tiago Franco; de Melo Loureiro, Ana Paula; Filho, Walter Dos Reis Pereira; Santos, Alcinéa Meigikos Dos Anjos; de Lima, Wothan Tavares; Farsky, Sandra Helena Poliselli

    2011-10-01

    Hydroquinone (HQ) is an environmental contaminant which causes immune toxicity. In this study, the effects of exposure to low doses of HQ on neutrophil mobilization into the LPS-inflamed lung were investigated. Male Swiss mice were exposed to aerosolized vehicle (control) or 12.5, 25 or 50ppm HQ (1h/day for 5 days). One hour later, oxidative burst, cell cycle, DNA fragmentation and adhesion molecules expressions in circulating neutrophils were determined by flow cytometry, and plasma malondialdehyde (MDA) levels were measured by HPLC. Also, 1h later the last exposures, inflammation was induced by LPS inhalation (0.1mg/ml/10min) and 3h later, the numbers of leukocytes in peripheral blood and in the bronchoalveolar lavage fluid (BALF) were determined using a Neubauer chamber and stained smears; adhesion molecules expressed on lung microvessel endothelial cells were quantified by immunohistochemistry; myeloperoxidase (MPO) activity was measured in the lung tissue by colorimetric assay; and cytokines in the BALF were determined by ELISA. In vivo HQ exposure augmented plasma MDA levels and oxidative activity of neutrophils, but did not cause alterations in cell cycle and DNA fragmentation. Under these conditions, the number of circulating leukocytes was not altered, but HQ exposure reduced LPS-induced neutrophil migration into the alveolar space, as these cells remained in the lung tissue. The impaired neutrophil migration into BALF may not be dependent on reduced cytokines secretions in the BALF and lung endothelial adhesion molecules expressions. However, HQ exposure increased the expression of β(2) and β(3) integrins and platelet-endothelial cell adhesion molecule-1 (PECAM-1) in neutrophils, which were not further enhanced by fMLP in vitro stimulation, indicating that HQ exposure activates circulating neutrophils, impairing further stimulatory responses. Therefore, it has been shown, for the first time, that neutrophils are target of lower levels of in vivo HQ

  5. Systemic inflammation, nutritional status and tumor immune microenvironment determine outcome of resected non-small cell lung cancer.

    Directory of Open Access Journals (Sweden)

    Marco Alifano

    Full Text Available BACKGROUND: Hypothesizing that nutritional status, systemic inflammation and tumoral immune microenvironment play a role as determinants of lung cancer evolution, the purpose of this study was to assess their respective impact on long-term survival in resected non-small cell lung cancers (NSCLC. METHODS AND FINDINGS: Clinical, pathological and laboratory data of 303 patients surgically treated for NSCLC were retrospectively analyzed. C-reactive protein (CRP and prealbumin levels were recorded, and tumoral infiltration by CD8+ lymphocytes and mature dendritic cells was assessed. We observed that factors related to nutritional status, systemic inflammation and tumoral immune microenvironment were correlated; significant correlations were also found between these factors and other relevant clinical-pathological parameters. With respect to outcome, at univariate analysis we found statistically significant associations between survival and the following variables: Karnofsky index, American Society of Anesthesiologists (ASA class, CRP levels, prealbumin concentrations, extent of resection, pathologic stage, pT and pN parameters, presence of vascular emboli, and tumoral infiltration by either CD8+ lymphocytes or mature dendritic cells and, among adenocarcinoma type, tumor grade (all p285 mg/L prealbumin levels and high (>96/mm2 CD8+ cell count had a 5-year survival rate of 80% [60.9-91.1] as compared to 18% [7.9-35.6] in patients with an opposite pattern of values. When stages I-II were considered alone, the prognostic significance of these factors was even more pronounced. CONCLUSIONS: Our data show that nutrition, systemic inflammation and tumoral immune contexture are prognostic determinants that, taken together, may predict outcome.

  6. Iron supplementation at high altitudes induces inflammation and oxidative injury to lung tissues in rats

    Energy Technology Data Exchange (ETDEWEB)

    Salama, Samir A., E-mail: salama.3@buckeyemail.osu.edu [High Altitude Research Center, Taif University, Al-Haweiah, Taif 21974 (Saudi Arabia); Department of Biochemistry, Faculty of Pharmacy, Al-Azhar University, Cairo 11751 (Egypt); Department of Pharmacology and GTMR Unit, College of Clinical Pharmacy, Taif University, Al-Haweiah, Taif 21974 (Saudi Arabia); Omar, Hany A. [Department of Pharmacology, Faculty of Pharmacy, Beni-Suef University, Beni-Suef 62514 (Egypt); Maghrabi, Ibrahim A. [Department of Clinical Pharmacy, College of Clinical Pharmacy, Taif University, Al-Haweiah, Taif 21974 (Saudi Arabia); AlSaeed, Mohammed S. [Department of Surgery, College of Medicine, Taif University, Al-Haweiah, Taif 21974 (Saudi Arabia); EL-Tarras, Adel E. [High Altitude Research Center, Taif University, Al-Haweiah, Taif 21974 (Saudi Arabia)

    2014-01-01

    Exposure to high altitudes is associated with hypoxia and increased vulnerability to oxidative stress. Polycythemia (increased number of circulating erythrocytes) develops to compensate the high altitude associated hypoxia. Iron supplementation is, thus, recommended to meet the demand for the physiological polycythemia. Iron is a major player in redox reactions and may exacerbate the high altitudes-associated oxidative stress. The aim of this study was to explore the potential iron-induced oxidative lung tissue injury in rats at high altitudes (6000 ft above the sea level). Iron supplementation (2 mg elemental iron/kg, once daily for 15 days) induced histopathological changes to lung tissues that include severe congestion, dilatation of the blood vessels, emphysema in the air alveoli, and peribronchial inflammatory cell infiltration. The levels of pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α), lipid peroxidation product and protein carbonyl content in lung tissues were significantly elevated. Moreover, the levels of reduced glutathione and total antioxidant capacity were significantly reduced. Co-administration of trolox, a water soluble vitamin E analog (25 mg/kg, once daily for the last 7 days of iron supplementation), alleviated the lung histological impairments, significantly decreased the pro-inflammatory cytokines, and restored the oxidative stress markers. Together, our findings indicate that iron supplementation at high altitudes induces lung tissue injury in rats. This injury could be mediated through excessive production of reactive oxygen species and induction of inflammatory responses. The study highlights the tissue injury induced by iron supplementation at high altitudes and suggests the co-administration of antioxidants such as trolox as protective measures. - Highlights: • Iron supplementation at high altitudes induced lung histological changes in rats. • Iron induced oxidative stress in lung tissues of rats at high altitudes. • Iron

  7. Lipoxin A4 and platelet activating factor are involved in E. coli or LPS-induced lung inflammation in CFTR-deficient mice.

    Directory of Open Access Journals (Sweden)

    Haiya Wu

    Full Text Available CFTR (cystic fibrosis transmembrane conductance regulator is expressed by both neutrophils and platelets. Lack of functional CFTR could lead to severe lung infection and inflammation. Here, we found that mutation of CFTR (F508del or inhibition of CFTR in mice led to more severe thrombocytopenia, alveolar neutrocytosis and bacteriosis, and lower lipoxin A4/MIP-2 (macrophage inhibitory protein-2 or lipoxin A4/neutrophil ratios in the BAL (bronchoalveolar lavage during acute E. coli pneumonia. In vitro, inhibition of CFTR promotes MIP-2 production in LPS-stimulated neutrophils; however, lipoxin A4 could dose-dependently suppress this effect. In LPS-induced acute lung inflammation, blockade of PSGL-1 (P-selectin glycoprotein ligand-1 or P-selectin, antagonism of PAF by WEB2086, or correction of mutated CFTR trafficking by KM11060 could significantly increase plasma lipoxin A4 levels in F508del relevant to wildtype mice. Concurrently, F508del mice had higher plasma platelet activating factor (PAF levels and PAF-AH activity compared to wildtype under LPS challenge. Inhibiting hydrolysis of PAF by a specific PAF-AH (PAF-acetylhydrolase inhibitor, MAFP, could worsen LPS-induced lung inflammation in F508del mice compared to vehicle treated F508del group. Particularly, depletion of platelets in F508del mice could significantly decrease plasma lipoxin A4 and PAF-AH activity and deteriorate LPS-induced lung inflammation compared to control F508del mice. Taken together, lipoxin A4 and PAF are involved in E. coli or LPS-induced lung inflammation in CFTR-deficient mice, suggesting that lipoxin A4 and PAF might be therapeutic targets for ameliorating CFTR-deficiency deteriorated lung inflammation.

  8. Is There a Regulatory Role of Immunoglobulins on Tissue Forming Cells Relevant in Chronic Inflammatory Lung Diseases?

    Directory of Open Access Journals (Sweden)

    Michael Roth

    2011-01-01

    Full Text Available Epithelial cells, fibroblasts and smooth muscle cells together form and give structure to the airway wall. These three tissue forming cell types are structure giving elements and participate in the immune response to inhaled particles including allergens and dust. All three cell types actively contribute to the pathogenesis of chronic inflammatory lung diseases such as asthma and chronic obstructive pulmonary disease (COPD. Tissue forming cells respond directly to allergens through activated immunoglobulins which then bind to their corresponding cell surface receptors. It was only recently reported that allergens and particles traffic through epithelial cells without modification and bind to the immunoglobulin receptors on the surface of sub-epithelial mesenchymal cells. In consequence, these cells secrete pro-inflammatory cytokines, thereby extending the local inflammation. Furthermore, activation of the immunoglobulin receptors can induce proliferation and tissue remodeling of the tissue forming cells. New studies using anti-IgE antibody therapy indicate that the inhibition of immunoglobulins reduces the response of tissue forming cells. The unmeasured questions are: (i why do tissue forming cells express immunoglobulin receptors and (ii do tissue forming cells process immunoglobulin receptor bound particles? The focus of this review is to provide an overview of the expression and function of various immunoglobulin receptors.

  9. Induction of Chronic Inflammation and Altered Levels of DNA Hydroxymethylation in Somatic and Germinal Tissues of CBA/CaJ Mice Exposed to (48)Ti Ions.

    Science.gov (United States)

    Rithidech, Kanokporn Noy; Jangiam, Witawat; Tungjai, Montree; Gordon, Chris; Honikel, Louise; Whorton, Elbert B

    2016-01-01

    Although the lung is one of the target organs at risk for cancer induction from exposure to heavy ions found in space, information is insufficient on cellular/molecular responses linked to increased cancer risk. Knowledge of such events may aid in the development of new preventive measures. Furthermore, although it is known that germinal cells are sensitive to X- or γ-rays, there is little information on the effects of heavy ions on germinal cells. Our goal was to investigate in vivo effects of 1 GeV/n (48)Ti ions (one of the important heavy ions found in the space environment) on somatic (lung) and germinal (testis) tissues collected at various times after a whole body irradiation of CBA/CaJ mice (0, 0.1, 0.25, or 0.5 Gy, delivered at 1 cGy/min). We hypothesized that (48)Ti-ion-exposure induced damage in both tissues. Lung tissue was collected from each mouse from each treatment group at 1 week, 1 month, and 6 months postirradiation. For the testis, we collected samples at 6 months postirradiation. Hence, only late-occurring effects of (48)Ti ions in the testis were studied. There were five mice per treatment group at each harvest time. We investigated inflammatory responses after exposure to (48)Ti ions by measuring the levels of activated nuclear factor kappa B and selected pro-inflammatory cytokines in both tissues of the same mouse. These measurements were coupled with the quantitation of the levels of global 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC). Our data clearly showed the induction of chronic inflammation in both tissues of exposed mice. A dose-dependent reduction in global 5hmC was found in the lung at all time-points and in testes collected at 6 months postirradiation. In contrast, significant increases in global 5mC were found only in lung and testes collected at 6 months postirradiation from mice exposed to 0.5 Gy of 1 GeV/n (48)Ti ions. Overall, our data showed that (48)Ti ions may create health risks in both

  10. The Glutathione Synthesis Gene Gclm Modulates Amphiphilic Polymer-Coated CdSe/ZnS Quantum Dot–Induced Lung Inflammation in Mice

    OpenAIRE

    Lisa A McConnachie; Dianne Botta; White, Collin C.; Chad S Weldy; Hui-Wen Wilkerson; Jianbo Yu; Russell Dills; Xiaozhong Yu; Griffith, William C.; Faustman, Elaine M; Farin, Federico M.; Gill, Sean E.; Parks, William C.; Xiaoge Hu; Xiaohu Gao

    2013-01-01

    Quantum dots (QDs) are unique semi-conductor fluorescent nanoparticles with potential uses in a variety of biomedical applications. However, concerns exist regarding their potential toxicity, specifically their capacity to induce oxidative stress and inflammation. In this study we synthesized CdSe/ZnS core/shell QDs with a tri-n-octylphosphine oxide, poly(maleic anhydride-alt-1-tetradecene) (TOPO-PMAT) coating and assessed their effects on lung inflammation in mice. Previously published in vi...

  11. Regulation of Arachidonic Acid Pathway and Eosinophilic Inflammation in Chronic Rhinosinusitis/ Nasal Polyposis. Potential Role of Staphylococcus aureus Enterotoxins

    OpenAIRE

    Pérez Novo, C

    2006-01-01

    linked to inflammation. Furthermore, EP2 and EP4 receptor expression was increased in chronic rhinosinusitis and nasal polyp subjects in contrast to EP1 and EP3, which were down regulated in the polyp group, suggesting a distinctive role of these receptors in the pathophysiology of nasal polyposis. Finally, based on our previous findings and parallel work of our group, we studied the influence of S. aureus enterotoxins in the regulation of both eosinophilic inflammatory and eicosanoid pathway...

  12. Coronary heart disease, chronic inflammation, and pathogenic social hierarchy: a biological limit to possible reductions in morbidity and mortality

    OpenAIRE

    Wallace, Rodrick; Wallace, Deborah; Robert G Wallace

    2003-01-01

    We suggest that a particular form of social hierarchy, which we characterize as 'pathogenic', can, from the earliest stages of life, exert a formal analog to evolutionary selection pressure, literally writing a permanent developmental image of itself upon immune function as chronic vascular inflammation and its consequences. The staged nature of resulting disease emerges 'naturally' as a rough analog to punctuated equilibrium in evolutionary theory, although selection pressure is a passive fi...

  13. Adipose inflammation initiates recruitment of leukocytes to mouse femoral artery: role of adipo-vascular axis in chronic inflammation.

    Directory of Open Access Journals (Sweden)

    Sumihiko Hagita

    Full Text Available BACKGROUND: Although inflammation within adipose tissues is known to play a role in metabolic syndrome, the causative connection between inflamed adipose tissue and atherosclerosis is not fully understood. In the present study, we examined the direct effects of adipose tissue on macro-vascular inflammation using intravital microscopic analysis of the femoral artery after adipose tissue transplantation. METHODS AND RESULTS: We obtained subcutaneous (SQ and visceral (VIS adipose tissues from C57BL/6 mice fed normal chow (NC or a high fat diet (HF, then transplanted the tissues into the perivascular area of the femoral artery of recipient C57/BL6 mice. Quantitative intravital microscopic analysis revealed an increase in adherent leukocytes after adipose tissue transplantation, with VIS found to induce significantly more leukocyte accumulation as compared to SQ. Moreover, adipose tissues from HF fed mice showed significantly more adhesion to the femoral artery. Simultaneous flow cytometry demonstrated upregulation of CD11b on peripheral granulocyte and monocytes after adipose tissue transplantation. We also observed dominant expressions of the inflammatory cytokine IL-6, and chemokines MCP-1 and MIP-1β in the stromal vascular fraction (SVF of these adipose tissues as well as sera of recipient mice after transplantation. Finally, massive accumulations of pro-inflammatory and dendritic cells were detected in mice with VIS transplantation as compared to SQ, as well as in HF mice as compared to those fed NC. CONCLUSION: Our in vivo findings indicate that adipose tissue stimulates leukocyte accumulation in the femoral artery. The underlying mechanisms involve upregulation of CD11b in leukocytes, induction of cytokines and chemokines, and accumulation of pro-inflammatory cells in the SVF.

  14. Donor dopamine treatment limits pulmonary oedema and inflammation in lung allografts subjected to prolonged hypothermia

    NARCIS (Netherlands)

    Hanusch, Christine; Nowak, Kai; Toerlitz, Patrizia; Gill, Ishar S.; Song, Hui; Rafat, Neysan; Brinkkoetter, Paul T.; Leuvenink, Henri G.; Van Ackern, Klaus C.; Yard, Benito A.; Beck, Grietje C.

    2008-01-01

    Background. Endothelial barrier dysfunction severely compromises organ function after reperfusion. Because dopamine pretreatment improves hypothermia mediated barrier dysfunction, we tested the hypothesis that dopamine treatment of lung allografts positively affects tissue damage associated with hyp

  15. Chronic Sleep Disruption Alters Gut Microbiota, Induces Systemic and Adipose Tissue Inflammation and Insulin Resistance in Mice

    Science.gov (United States)

    Poroyko, Valeriy A.; Carreras, Alba; Khalyfa, Abdelnaby; Khalyfa, Ahamed A.; Leone, Vanessa; Peris, Eduard; Almendros, Isaac; Gileles-Hillel, Alex; Qiao, Zhuanhong; Hubert, Nathaniel; Farré, Ramon; Chang, Eugene B.; Gozal, David

    2016-01-01

    Chronic sleep fragmentation (SF) commonly occurs in human populations, and although it does not involve circadian shifts or sleep deprivation, it markedly alters feeding behaviors ultimately promoting obesity and insulin resistance. These symptoms are known to be related to the host gut microbiota. Mice were exposed to SF for 4 weeks and then allowed to recover for 2 weeks. Taxonomic profiles of fecal microbiota were obtained prospectively, and conventionalization experiments were performed in germ-free mice. Adipose tissue insulin sensitivity and inflammation, as well as circulating measures of inflammation, were assayed. Effect of fecal water on colonic epithelial permeability was also examined. Chronic SF-induced increased food intake and reversible gut microbiota changes characterized by the preferential growth of highly fermentative members of Lachnospiraceae and Ruminococcaceae and a decrease of Lactobacillaceae families. These lead to systemic and visceral white adipose tissue inflammation in addition to altered insulin sensitivity in mice, most likely via enhanced colonic epithelium barrier disruption. Conventionalization of germ-free mice with SF-derived microbiota confirmed these findings. Thus, SF-induced metabolic alterations may be mediated, in part, by concurrent changes in gut microbiota, thereby opening the way for gut microbiome-targeted therapeutics aimed at reducing the major end-organ morbidities of chronic SF. PMID:27739530

  16. Protective effects of isolated polyphenolic and alkaloid fractions of Ruta graveolens L. on acute and chronic models of inflammation.

    Science.gov (United States)

    Ratheesh, M; Shyni, G L; Sindhu, G; Helen, A

    2010-02-01

    Ruta graveolens L. (Rutaceae) are traditionally used for the treatment of rheumatism, arthritis and other inflammatory conditions in the traditional medicine of India, were evaluated for their protective effect in acute and chronic models of inflammation. Carrageenan induced rat paw edema and adjuvant induced arthritis were employed as the experimental models of acute and chronic inflammation respectively. Isolated polyphenolic and alkaloid fraction (AFR) from Ruta graveolens and evaluated its anti inflammatory activity in carrageenan induced acute model. AFR with a dose 10 mg/kg showed higher anti inflammatory effect than polyphenols and standard drug diclofenec. AFR significantly decreased the paw edema in arthritic rats. TBARS, COX-2, 5-LOX and MPO level were decreased and the levels of antioxidant enzymes and GSH level were increased on treatment with AFR. The increment in CRP level and ceruloplasmin level observed in arthritic animals were also found to be significantly restored in AFR treated rats. The results demonstrated the potential beneficiary effect of isolated polyphenolic and alkaloid fraction of Ruta graveolens L. on acute and chronic models of inflammation in rats.

  17. Taraxasterol inhibits cigarette smoke-induced lung inflammation by inhibiting reactive oxygen species-induced TLR4 trafficking to lipid rafts.

    Science.gov (United States)

    Xueshibojie, Liu; Duo, Yu; Tiejun, Wang

    2016-10-15

    Taraxasterol, a pentacyclic-triterpene isolated from Taraxacum officinale, has been demonstrated to have anti-inflammatory effects. However, the protective effects of taraxasterol against cigarette smoke (CS)-induced lung inflammation have not been reported. This study aimed to investigate the protective effects and mechanism of taraxasterol on CS-induced lung inflammation in mice. CS-induced mouse lung inflammation model was used to investigate the protective effects of taraxasterol in vivo. Human bronchial epithelial cells (HBECs) were used to investigate the protective mechanism of taraxasterol in vitro. The results showed that taraxasterol attenuated CS-induced lung pathological changes, inflammatory cells infiltration, inflammatory cytokines TNF-α, IL-6 and IL-1β production. Taraxasterol also up-regulated CS-induced glutathione (GSH) production. In vitro, taraxasterol was found to inhibit CS-induced reactive oxygen species production, recruitment of TLR4 into lipid rafts, NF-κB activation, and IL-8 production. Furthermore, our results showed that antioxidant N-acetyl-L-cysteine (NAC) significantly inhibited CS-induced recruitment of TLR4 into lipid rafts as well as IL-8 production. In conclusion, our results suggested that taraxasterol had protective effects of CS-induced lung inflammation.

  18. Inflammation and lung maturation from stretch injury in preterm fetal sheep

    OpenAIRE

    Hillman, Noah H.; Graeme R Polglase; Jane Pillow, J.; Saito, Masatoshi; Suhas G Kallapur; Alan H Jobe

    2010-01-01

    Mechanical ventilation is a risk factor for the development of bronchopulmonary dysplasia in premature infants. Fifteen minutes of high tidal volume (Vt) ventilation induces inflammatory cytokine expression in small airways and lung parenchyma within 3 h. Our objective was to describe the temporal progression of cytokine and maturation responses to lung injury in fetal sheep exposed to a defined 15-min stretch injury. After maternal anesthesia and hysterotomy, 129-day gestation fetal lambs (n...

  19. TRPV4 inhibition counteracts edema and inflammation and improves pulmonary function and oxygen saturation in chemically induced acute lung injury.

    Science.gov (United States)

    Balakrishna, Shrilatha; Song, Weifeng; Achanta, Satyanarayana; Doran, Stephen F; Liu, Boyi; Kaelberer, Melanie M; Yu, Zhihong; Sui, Aiwei; Cheung, Mui; Leishman, Emma; Eidam, Hilary S; Ye, Guosen; Willette, Robert N; Thorneloe, Kevin S; Bradshaw, Heather B; Matalon, Sadis; Jordt, Sven-Eric

    2014-07-15

    The treatment of acute lung injury caused by exposure to reactive chemicals remains challenging because of the lack of mechanism-based therapeutic approaches. Recent studies have shown that transient receptor potential vanilloid 4 (TRPV4), an ion channel expressed in pulmonary tissues, is a crucial mediator of pressure-induced damage associated with ventilator-induced lung injury, heart failure, and infarction. Here, we examined the effects of two novel TRPV4 inhibitors in mice exposed to hydrochloric acid, mimicking acid exposure and acid aspiration injury, and to chlorine gas, a severe chemical threat with frequent exposures in domestic and occupational environments and in transportation accidents. Postexposure treatment with a TRPV4 inhibitor suppressed acid-induced pulmonary inflammation by diminishing neutrophils, macrophages, and associated chemokines and cytokines, while improving tissue pathology. These effects were recapitulated in TRPV4-deficient mice. TRPV4 inhibitors had similar anti-inflammatory effects in chlorine-exposed mice and inhibited vascular leakage, airway hyperreactivity, and increase in elastance, while improving blood oxygen saturation. In both models of lung injury we detected increased concentrations of N-acylamides, a class of endogenous TRP channel agonists. Taken together, we demonstrate that TRPV4 inhibitors are potent and efficacious countermeasures against severe chemical exposures, acting against exaggerated inflammatory responses, and protecting tissue barriers and cardiovascular function. PMID:24838754

  20. Cigarette smoke activates the proto-oncogene c-src to promote airway inflammation and lung tissue destruction.

    Science.gov (United States)

    Geraghty, Patrick; Hardigan, Andrew; Foronjy, Robert F

    2014-03-01

    The diagnosis of chronic obstructive pulmonary disease (COPD) confers a 2-fold increased lung cancer risk even after adjusting for cigarette smoking, suggesting that common pathways are operative in both diseases. Although the role of the tyrosine kinase c-Src is established in lung cancer, less is known about its impact in other lung diseases, such as COPD. This study examined whether c-Src activation by cigarette smoke contributes to the pathogenesis of COPD. Cigarette smoke increased c-Src activity in human small airway epithelial (SAE) cells from healthy donors and in the lungs of exposed mice. Similarly, higher c-Src activation was measured in SAE cells from patients with COPD compared with healthy control subjects. In SAE cells, c-Src silencing or chemical inhibition prevented epidermal growth factor (EGF) receptor signaling in response to cigarette smoke but not EGF stimulation. Further studies showed that cigarette smoke acted through protein kinase C α to trigger c-Src to phosphorylate EGF receptor and thereby to induce mitogen-activated protein kinase responses in these cells. To further investigate the role of c-Src, A/J mice were orally administered the specific Src inhibitor AZD-0530 while they were exposed to cigarette smoke for 2 months. AZD-0530 treatment blocked c-Src activation, decreased macrophage influx, and prevented airspace enlargement in the lungs of cigarette smoke-exposed mice. Moreover, inhibiting Src deterred the cigarette smoke-mediated induction of matrix metalloproteinase-9 and -12 in alveolar macrophages and lung expression of cathepsin K, IL-17, TNF-α, MCP-1, and KC, all key factors in the pathogenesis of COPD. These results indicate that activation of the proto-oncogene c-Src by cigarette smoke promotes processes linked to the development of COPD. PMID:24111605

  1. Chronic hepatitis E infection in lung transplant recipients

    NARCIS (Netherlands)

    Riezebos-Brilman, Annelies; Puchhammer-Stockl, Elisabeth; van der Weide, Hinke Y.; Haagsma, Elizabeth B.; Jaksch, Peter; Bejvl, Isabella; Niesters, Hubert G.; Verschuuren, Erik A. M.

    2013-01-01

    BACKGROUND: Hepatitis E virus (HEV) genotype 3 has been identified in patients with autochthonous HEV infections in developed countries and is currently being recognized as an emerging zoonotic pathogen. HEV infection may lead to a chronic hepatitis in immune-compromised patients. METHODS: We studie

  2. Radioaerosol lung scanning in chronic obstructive pulmonary disease (COPD) and related disorders

    International Nuclear Information System (INIS)

    As a coordinated research project of the International Atomic Energy Agency (IAEA), a multicentre joint study on radioaerosol lung scan using the BARC nebulizer has prospectively been carried out during 1988-1992 with the participation of 10 member countries in Asia [Bangladesh, China, India, Indonesia, Japan, Korea, Pakistan, Philippines, Singapore and Thailand]. The study was designed so that it would primarily cover chronic obstructive pulmonary disease (COPD) and the other related and common pulmonary diseases. The study also included normal controls and asymptomatic smokers. The purposes of this presentation are three fold: firstly, to document the usefulness of the nebulizer and the validity of user's protocol in imaging COPD and other lung diseases; secondly, to discuss scan features of the individual COPD and other disorders studied and thirdly, to correlate scan alterations with radiographic findings. Before proceeding with a systematic analysis of aerosol scan patterns in the disease groups, we documented normal pattern. The next step was the assessment of scan features in those who had been smoking for more than several years but had no symptoms or signs referable to airways. The lung diseases we analyzed included COPD [emphysema, chronic bronchitis, asthma and bronchiectasis], bronchial obstruction, compensatory overinflation and other common lung diseases such as lobar pneumonia, tuberculosis, interstitial fibrosis, diffuse panbronchiolitis, lung edema and primary and metastatic lung cancers. Lung embolism, inhalation bums and glue-sniffer's lung are separately discussed by Dr. Sundram of Singapore elsewhere in this book. The larger portion of this chapter is allocated to the discussion of COPD with a special effort made in sorting out differential scan features. Diagnostic criteria in individual COPD were defined for each category of disease and basic clinical symptoms and signs and pertinent laboratory data as well as radiographic manifestations are

  3. Chronic obstructive pulmonary disease and altered risk of lung cancer in a population-based case-control study.

    Directory of Open Access Journals (Sweden)

    Jill Koshiol

    Full Text Available BACKGROUND: Chronic obstructive pulmonary disease (COPD has been consistently associated with increased risk of lung cancer. However, previous studies have had limited ability to determine whether the association is due to smoking. METHODOLOGY/PRINCIPAL FINDINGS: The Environment And Genetics in Lung cancer Etiology (EAGLE population-based case-control study recruited 2100 cases and 2120 controls, of whom 1934 cases and 2108 controls reported about diagnosis of chronic bronchitis, emphysema, COPD (chronic bronchitis and/or emphysema, or asthma more than 1 year before enrollment. We estimated odds ratios (OR and 95% confidence intervals (CI using logistic regression. After adjustment for smoking, other previous lung diseases, and study design variables, lung cancer risk was elevated among individuals with a history of chronic bronchitis (OR = 2.0, 95% CI = 1.5-2.5, emphysema (OR = 1.9, 95% CI = 1.4-2.8, or COPD (OR = 2.5, 95% CI = 2.0-3.1. Among current smokers, association between chronic bronchitis and lung cancer was strongest among lighter smokers. Asthma was associated with a decreased risk of lung cancer in males (OR = 0.48, 95% CI = 0.30-0.78. CONCLUSIONS/SIGNIFICANCE: These results suggest that the associations of personal history of chronic bronchitis, emphysema, and COPD with increased risk of lung cancer are not entirely due to smoking. Inflammatory processes may both contribute to COPD and be important for lung carcinogenesis.

  4. Clinical approach to chronic beryllium disease and other nonpneumoconiotic interstitial lung diseases.

    Science.gov (United States)

    Maier, Lisa A

    2002-10-01

    Exposures in the workplace result in a diverse set of diseases ranging from the pneumoconiosis to other interstitial lung diseases to acute lung injury. Physician awareness of the potential disease manifestations associated with specific exposures is important in defining these diseases and in preventing additional disease. Most occupational diseases mimic other forms of lung disease, including pulmonary fibrosis, sarcoidosis, adult respiratory distress syndrome (ARDS), and bronchiolitis. A "sarcoidosis"-like syndrome, usually limited to the lungs, may result from exposure to bioaerosols and a number of metals. Exposure to beryllium in the workplace produces a granulomatous lung disease clinically indistinguishable from sarcoidosis, chronic beryllium disease (CBD). Beryllium's ability to produce a beryllium-specific immune response is used in the beryllium lymphocyte proliferation tests to confirm a diagnosis of CBD and exclude sarcoidosis. Exposure to other metals must also be considered in the differential diagnosis of sarcoidosis. When an individual presents acutely with ARDS or acute lung injury, an acute inhalational exposure must be considered. Exposure to a number of irritant substances at high levels may cause a "chemical pneumonitis" or acute lung injury, depending on the solubility and physicochemical properties of the substance. Some of the most notable agents include nitrogen and sulfur oxides, phosgene, and smoke breakdown products. Ingestion of paraquat may also result in an ARDS syndrome, with pulmonary fibrosis eventually resulting. Bronchiolitis is a rare manifestation of inhalational exposures but must also be considered in the clinical evaluation of inhalational exposure. PMID:12362066

  5. The lung microbiome in moderate and severe chronic obstructive pulmonary disease.

    Directory of Open Access Journals (Sweden)

    Alexa A Pragman

    Full Text Available Chronic obstructive pulmonary disease (COPD is an inflammatory disorder characterized by incompletely reversible airflow obstruction. Bacterial infection of the lower respiratory tract contributes to approximately 50% of COPD exacerbations. Even during periods of stable lung function, the lung harbors a community of bacteria, termed the microbiome. The role of the lung microbiome in the pathogenesis of COPD remains unknown. The COPD lung microbiome, like the healthy lung microbiome, appears to reflect microaspiration of oral microflora. Here we describe the COPD lung microbiome of 22 patients with Moderate or Severe COPD compared to 10 healthy control patients. The composition of the lung microbiomes was determined using 454 pyrosequencing of 16S rDNA found in bronchoalveolar lavage fluid. Sequences were analyzed using mothur, Ribosomal Database Project, Fast UniFrac, and Metastats. Our results showed a significant increase in microbial diversity with the development of COPD. The main phyla in all samples were Actinobacteria, Firmicutes, and Proteobacteria. Principal coordinate analyses demonstrated separation of control and COPD samples, but samples did not cluster based on disease severity. However, samples did cluster based on the use of inhaled corticosteroids and inhaled bronchodilators. Metastats analyses demonstrated an increased abundance of several oral bacteria in COPD samples.

  6. Lung transplantation in chronic obstructive pulmonary disease: patient selection and special considerations

    Directory of Open Access Journals (Sweden)

    Lane CR

    2015-10-01

    Full Text Available C Randall Lane, Adriano R Tonelli Respiratory Institute, Cleveland Clinic, Cleveland, OH, USA Abstract: Chronic obstructive pulmonary disease (COPD is a leading cause of mortality and morbidity. Lung transplantation is one of the few treatments available for end-stage COPD with the potential to improve survival and quality of life. The selection of candidates and timing of listing present challenges, as COPD tends to progress fairly slowly, and survival after lung transplantation remains limited. Though the natural course of COPD is difficult to predict, the use of assessments of functional status and multivariable indices such as the BODE index can help identify which patients with COPD are at increased risk for mortality, and hence which are more likely to benefit from lung transplantation. Patients with COPD can undergo either single or bilateral lung transplantation. Although many studies suggest better long-term survival with bilateral lung transplant, especially in younger patients, this continues to be debated, and definitive recommendations about this cannot be made. Patients may be more susceptible to particular complications of transplant for COPD, including native lung hyperinflation, and development of lung cancer. Keywords: emphysema, pulmonary hypertension, mortality, prognosis, outcomes, alpha-1 antitrypsin deficiency

  7. Comparison of Serum Lipid Levels in Chronic Obstructive Pulmonary Disease and Lung Cancer

    Directory of Open Access Journals (Sweden)

    Mehmet Kos

    2016-01-01

    Full Text Available Aim: Relationship between serum lipid level in chronic obstructive lung disease (COLD and lung cancer was not well documented. In our study we planned to compare serum lipid levels (Total Cholesterol-TC, low density lipoprotein cholesterol-LDL-C, trigliseride-TGL, and high density lipoprotein cholesterol-HDL-C in these common diseases. Material and Method: We evaluated 100 patients and 50 control group retrospectively. We enrolled the lipid parameters before any medical treatment start. Student%u2019s t-test and one-way ANOVA test was used for comparison of the patient characteristics and mean cholesterol level. Results: TC levels were higher in COLD disease than lung cancer group but not statistically significant. TGL levels were higher in lung cancer group than COLD and control group but this was also not statistically significant. Mild-moderate degree COLD patients had lower HDL-C than severe COLD patients (p=0.02. But TC and TGL levels were lower in severe COLD pateints. Small cell lung sancer and non-small lung cancers had statistically significantly lower TC and TGL levels (respectively p=0.04 and p=0.02. Discussion: We estimated that lipid leves of at the beginning of COLD were decreased to provide lipid necessity in cancer tissue due to tumor rapid cell proliferation in cancer, tumor cachexia and increased nutrition problems when developed lung cancer. Larger prospective studies are required to more accurate assessment this issue.

  8. Lung transplantation in chronic obstructive pulmonary disease: patient selection and special considerations.

    Science.gov (United States)

    Lane, C Randall; Tonelli, Adriano R

    2015-01-01

    Chronic obstructive pulmonary disease (COPD) is a leading cause of mortality and morbidity. Lung transplantation is one of the few treatments available for end-stage COPD with the potential to improve survival and quality of life. The selection of candidates and timing of listing present challenges, as COPD tends to progress fairly slowly, and survival after lung transplantation remains limited. Though the natural course of COPD is difficult to predict, the use of assessments of functional status and multivariable indices such as the BODE index can help identify which patients with COPD are at increased risk for mortality, and hence which are more likely to benefit from lung transplantation. Patients with COPD can undergo either single or bilateral lung transplantation. Although many studies suggest better long-term survival with bilateral lung transplant, especially in younger patients, this continues to be debated, and definitive recommendations about this cannot be made. Patients may be more susceptible to particular complications of transplant for COPD, including native lung hyperinflation, and development of lung cancer. PMID:26491282

  9. Detection and Severity Scoring of Chronic Obstructive Pulmonary Disease Using Volumetric Analysis of Lung CT Images

    International Nuclear Information System (INIS)

    Chronic obstructive pulmonary disease (COPD) is a devastating disease.While there is no cure for COPD and the lung damage associated with this disease cannot be reversed, it is still very important to diagnose it as early as possible. In this paper, we propose a novel method based on the measurement of air trapping in the lungs from CT images to detect COPD and to evaluate its severity. Twenty-five patients and twelve normal adults were included in this study. The proposed method found volumetric changes of the lungs from inspiration to expiration. To this end, trachea CT images at full inspiration and expiration were compared and changes in the areas and volumes of the lungs between inspiration and expiration were used to define quantitative measures (features). Using these features,the subjects were classified into two groups of normal and COPD patients using a Bayesian classifier. In addition, t-tests were applied to evaluate discrimination powers of the features for this classification. For the cases studied, the proposed method estimated air trapping in the lungs from CT images without human intervention. Based on the results, a mathematical model was developed to relate variations of lung volumes to the severity of the disease. As a computer aided diagnosis (CAD) system, the proposed method may assist radiologists in the detection of COPD. It quantifies air trapping in the lungs and thus may assist them with the scoring of the disease by quantifying the severity of the disease

  10. Regulation of Th17/Treg function contributes to the attenuation of chronic airway inflammation by icariin in ovalbumin-induced murine asthma model.

    Science.gov (United States)

    Wei, Ying; Liu, Baojun; Sun, Jing; Lv, Yubao; Luo, Qingli; Liu, Feng; Dong, Jingcheng

    2015-06-01

    Icariin which is a flavonoid glucoside isolated from Epimedium brevicornu Maxim, has been reported to have anti-osteoporotic, anti-inflammatory and anti-depressant-like activities. In this study, we observed the effect of icariin on airway inflammation of ovalbumin (OVA)-induced murine asthma model and the associated regulatory mode on T-helper (Th)17 and regulatory T (Treg) cell function. Our data revealed that chronic OVA inhalation induced a dramatic increase in airway resistance (RL) and decrease in the lung dynamic compliance (Cdyn), and icariin and DEX treatment caused significant attenuation of such airway hyperresponsiveness (AHR). BALF cell counts demonstrated that icariin and DEX led to a prominent reduction in total leukocyte as well as lymphocyte, eosinophil, neutrophil, basophil and monocyte counts. Histological analysis results indicated that icariin and DEX alleviated the inflammatory cells infiltrating into the peribronchial tissues and goblet cells hyperplasia and mucus hyper-production. Flow cytometry test demonstrated that icariin or DEX administration resulted in a significant percentage reduction in CD4+RORγt+ T cells and elevation of CD4+Foxp3+ T cells in BALF. Furthermore, icariin or DEX caused a significant reduction in IL-6, IL-17 and TGF-β level in BALF. Unfortunately, icariin had no effect on IL-10 level in BALF. Western blot assay found that icariin or DEX suppressed RORγt and promoted Foxp3 expression in the lung tissue. qPCR analysis revealed that icariin and DEX resulted in a notable decrease in RORγt and increase in Foxp3 mRNA expression in isolated spleen CD4+ T cell. In conclusion, our results suggested that icariin was effective in the attenuation of AHR and chronic airway inflammatory changes in OVA-induced murine asthma model, and this effect was associated with regulation of Th17/Treg responses, which indicated that icariin may be used as a potential therapeutic method to treat asthma with Th17/Treg imbalance phenotype

  11. Absolute quantification of serum microRNA-122 and its correlation with liver inflammation grade and serum alanine aminotransferase in chronic hepatitis C patients

    Directory of Open Access Journals (Sweden)

    Jiang-hua Wang

    2015-01-01

    Conclusions: The present study showed that serum microRNA-122 was elevated in acute and chronic hepatitis patients. However, this biomarker for acute liver injury did not reflect the liver inflammation activity in CHC patients.

  12. Obesity-induced chronic inflammation in C57Bl6J mice, a novel risk factor in the progression of renal AA amyloidosis?

    OpenAIRE

    Heijden, R.A. van der; Sheedfar, F.; Bijzet, J; Hazenberg, B P; Koonen, D.P.; Heeringa, P.

    2015-01-01

    Background: Compelling evidence links obesity induced systemic inflammation to the development of chronic kidney disease (CKD). This systemic inflammation may result from exacerbated adipose inflammation. Besides the known detrimental effects of typical pro-inflammatory factors secreted by the adipose tissue (TNF-α, MCP-1 and IL-6) on the kidney, we hypothesize the enhanced obesity-induced secretion of serum amyloid A (SAA), an acute inflammatory protein, to play a key role in aggravating obe...

  13. Chronic Inflammation: Synergistic Interactions of Recruiting Macrophages (TAMs and Eosinophils (Eos with Host Mast Cells (MCs and Tumorigenesis in CALTs. M-CSF, Suitable Biomarker for Cancer Diagnosis!