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Sample records for desflurane induces airway

  1. ED50 of desflurane for laryngeal mask airway removal in anaesthetised adults.

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    Makkar, J K; Arora, S; Jain, K; Wig, J

    2011-09-01

    Previous estimates for the end-tidal concentration of desflurane that allows removal of the laryngeal mask airway in 50% of anaesthetised adults (ED50) have ranged from 2.1% to 5.3%. To assess which value is correct, we studied 32 female patients (aged 30-50 years) undergoing intracavity caesium implants for cervical carcinoma under general anaesthesia. Anaesthesia was induced with propofol 2-3 mg.kg(-1) and maintained with desflurane in a 50% nitrous oxide-oxygen mixture. At the end of surgery, a predetermined target end-tidal desflurane concentration (starting at 4%) was maintained for 10 min using Dixon's up-down method and the laryngeal mask airway was removed. The target end-tidal concentration in the next patient was increased or decreased by 0.5% depending upon the response of the previous patient. Removal of the laryngeal mask airway without coughing, clenching, biting, movement or any adverse airway event during or within 1 min after removal was considered to be successful. We found that the laryngeal mask airway can be successfully removed in 50% (ED50) and 95% (ED95) of the anaesthetised adults at end-tidal desflurane concentrations of 2.4% (95% CI 1.3-2.9) and 3.8% (3.1-9.6), respectively.

  2. Desflurane for ambulatory anaesthesia: A comparison with sevoflurane for recovery profile and airway responses

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    Kajal Sachin Dalal

    2017-01-01

    Full Text Available Background and Aims: Desflurane and sevoflurane have low blood gas solubility co-efficients, allowing a rapid awakening from anaesthesia. However, desfluraneis pungent and may cause airway irritability. We compared desflurane and sevoflurane with respect to recovery and occurrence of adverse airway responses in spontaneously breathing patients while using the ProSeal™ laryngeal mask airway (LMA. Methods: Ninety-four adult patients undergoing hysteroscopic procedures were divided into sevoflurane (S group or desflurane (D group. Patients were premedicated with midazolam 0.03 mg/kg and fentanyl 1μg/kg. Anaesthesia was induced with propofol 2.0–2.5 mg/kg, followed by insertion of a ProSeal™ LMA. Adverse airway responses such as cough, hiccups, laryngospasm and breathholding were recorded. In the post-operative period: time to awakening, response to verbal commands, orientation, ability to sit with support and the recovery room Aldrete score were recorded. Results: Three patients in group S (6.4% and six patients (13.3% in Group D had adverse airway events. The mean time to eye opening (Group S-10.75 ± 7.54 min, Group D-4.94 ± 1.74 min, obeying verbal commands (Group S-13.13 ± 8.75 min, Group D-6.55 ± 1.75 min, orientation (Group S-15.42 ± 8.46 min, Group D-6.23 ± 2.4 min and to sit with support (Group S-36.09 ± 12.68 min, Group D-14.35 ± 3.75 min were found to be lesser with desflurane than with sevoflurane (P < 0.001. The mean time to recovery was delayed in Group S-46.00 ± 12.86 min compared to Group D-26.44 ± 5.33 min (P < 0.001. Conclusion: Desflurane has faster awakening properties than sevoflurane without an increase in adverse airway events when used during spontaneous ventilation through a ProSeal™ LMA along with propofol and fentanyl.

  3. Effective dose 50 of desflurane for laryngeal mask airway removal in anaesthetized children in cataract surgeries with subtenon block

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    Sameer Sethi

    2015-01-01

    Full Text Available Background: Quantification of the depth of desflurane anesthesia required for laryngeal mask airway (LMA removal in children has been done with the use of intravenous fentanyl or caudal anesthesia. This study aimed to determine the end-tidal concentration of desflurane required for LMA removal in children without the use of caudal or opioid analgesia in children undergoing elective cataract surgery. Materials and Methods: Our study enrolled 25 American Society of Anesthesiologists I and II children aged 2-10 years, undergoing elective cataract surgery. Anesthesia was induced with sevoflurane and oxygen/nitrous oxide using face mask and a size 2 LMA inserted. A subtenon block was administered in all children before surgical incision. Desflurane was used for maintenance of anesthesia. Predetermined end tidal concentration of desflurane was maintained for 10 min at the end of surgery before LMA removal was attempted. End tidal concentrations were increased/decreased using the Dixon up-down method (with 0.5% as a step size in the next patient depending on the previous patient′s response. Patient responses to LMA removal were classified as "movement" or "no movement." Results: 50% effective dose (ED 50 for successful removal of the LMA with desflurane in the presence of subtenon block was 3.6% (3.20-3.97% and that the 95% ED 95 was 4.648% (4.15-6.47%. Conclusion: Laryngeal mask airway removal can be successfully accomplished in 50% and 95% anesthetized children at 3.6% and 4.65% end-tidal desflurane concentration.

  4. Bradykinin and adenosine receptors mediate desflurane induced postconditioning in human myocardium: role of reactive oxygen species

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    Gérard Jean-Louis

    2010-07-01

    Full Text Available Abstract Background Desflurane during early reperfusion has been shown to postcondition human myocardium, in vitro. We investigated the role of adenosine and bradykinin receptors, and generation of radical oxygen species in desflurane-induced postconditioning in human myocardium. Methods We recorded isometric contraction of human right atrial trabeculae hanged in an oxygenated Tyrode's solution (34 degrees Celsius, stimulation frequency 1 Hz. After a 30-min hypoxic period, desflurane 6% was administered during the first 5 min of reoxygenation. Desflurane was administered alone or with pretreatment of N-mercaptopropionylglycine, a reactive oxygen species scavenger, 8-(p-Sulfophenyltheophylline, an adenosine receptor antagonist, HOE140, a selective B2 bradykinin receptor antagonist. In separate groups, adenosine and bradykinin were administered during the first minutes of reoxygenation alone or in presence of N-mercaptopropionylglycine. The force of contraction of trabeculae was recorded continuously. Developed force at the end of a 60-min reoxygenation period was compared (mean ± standard deviation between the groups by a variance analysis and post hoc test. Results Desflurane 6% (84 ± 6% of baseline enhanced the recovery of force after 60-min of reoxygenation as compared to control group (51 ± 8% of baseline, P N-mercaptopropionylglycine (54 ± 3% of baseline, 8-(p-Sulfophenyltheophylline (62 ± 9% of baseline, HOE140 (58 ± 6% of baseline abolished desflurane-induced postconditioning. Adenosine (80 ± 9% of baseline and bradykinin (83 ± 4% of baseline induced postconditioning (P vs control, N-mercaptopropionylglycine abolished the beneficial effects of adenosine and bradykinin (54 ± 8 and 58 ± 5% of baseline, respectively. Conclusions In vitro, desflurane-induced postconditioning depends on reactive oxygen species production, activation of adenosine and bradykinin B2 receptors. And, the cardioprotective effect of adenosine and bradykinin

  5. Desflurane preconditioning induces oscillation of NF-κB in human umbilical vein endothelial cells.

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    Juan Yi

    Full Text Available BACKGROUND: Nuclear factor kappa B (NF-κB has been implicated in anesthetic preconditioning (APC induced protection against anoxia and reoxygenation (A/R injury. The authors hypothesized that desflurane preconditioning would induce NF-κB oscillation and prevent endothelial cells apoptosis. METHODS: A human umbilical vein endothelial cells (HUVECs A/R injury model was used. A 30 minute desflurane treatment was initiated before anoxia. NF-κB inhibitor BAY11-7082 was administered in some experiments before desflurane preconditioning. Cells apoptosis was analyzed by flow cytometry using annexin V-fluorescein isothiocyanate staining and cell viability was evaluated by modified tertrozalium salt (MTT assay. The cellular superoxide dismutases (SOD activitiy were tested by water-soluble tetrazolium salt (WST-1 assay. NF-κB p65 subunit nuclear translocation was detected by immunofluorescence staining. Expression of inhibitor of NF-κB-α (IκBα, NF-κB p65 and cellular inhibitor of apoptosis 1 (c-IAP1, B-cell leukemia/lymphoma 2 (Bcl-2, cysteine containing aspartate specific protease 3 (caspases-3 and second mitochondrial-derived activator of caspase (SMAC/DIABLO were determined by western blot. RESULTS: Desflurane preconditioning caused phosphorylation and nuclear translocation of NF-κB before anoxia, on the contrary, induced the synthesis of IκBα and inhibition of NF-κB after reoxygenation. Desflurane preconditioning up-regulated the expression of c-IAP1 and Bcl-2, blocked the cleavage of caspase-3 and reduced SMAC release, and decreased the cell death of HUVECs after A/R. The protective effect was abolished by BAY11-7082 administered before desflurane. CONCLUSIONS: The results demonstrated that desflurane activated NF-κB during the preconditioning period and inhibited excessive activation of NF-κB in reperfusion. And the oscillation of NF-κB induced by desflurane preconditioning finally up-regulated antiapoptotic proteins expression and

  6. Aromatase inhibition attenuates desflurane-induced preconditioning against acute myocardial infarction in male mouse heart in vivo.

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    Virginija Jazbutyte

    Full Text Available The volatile anesthetic desflurane (DES effectively reduces cardiac infarct size following experimental ischemia/reperfusion injury in the mouse heart. We hypothesized that endogenous estrogens play a role as mediators of desflurane-induced preconditioning against myocardial infarction. In this study, we tested the hypothesis that desflurane effects local estrogen synthesis by modulating enzyme aromatase expression and activity in the mouse heart. Aromatase metabolizes testosterone to 17β- estradiol (E2 and thereby significantly contributes to local estrogen synthesis. We tested aromatase effects in acute myocardial infarction model in male mice. The animals were randomized and subjected to four groups which were pre-treated with the selective aromatase inhibitor anastrozole (A group and DES alone (DES group or in combination (A+DES group for 15 minutes prior to surgical intervention whereas the control group received 0.9% NaCl (CON group. All animals were subjected to 45 minutes ischemia following 180 minutes reperfusion. Anastrozole blocked DES induced preconditioning and increased infarct size compared to DES alone (37.94 ± 15.5% vs. 17.1 ± 3.62% without affecting area at risk and systemic hemodynamic parameters following ischemia/reperfusion. Protein localization studies revealed that aromatase was abundant in the murine cardiovascular system with the highest expression levels in endothelial and smooth muscle cells. Desflurane application at pharmacological concentrations efficiently upregulated aromatase expression in vivo and in vitro. We conclude that desflurane efficiently regulates aromatase expression and activity which might lead to increased local estrogen synthesis and thus preserve cellular integrity and reduce cardiac damage in an acute myocardial infarction model.

  7. Effects of desflurane on cerebral autoregulation.

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    Bedforth, N M; Girling, K J; Skinner, H J; Mahajan, R P

    2001-08-01

    The aim of this study was to determine the effects of desflurane, at 1 and 1.5 MAC, on cerebral autoregulation. Data were analysed from eight patients undergoing non-neurosurgical procedure. The blood flow velocity in the middle cerebral artery was measured by transcranial Doppler ultrasound and cerebral autoregulation was assessed by the transient hyperaemic response test. Partial pressure of the end-tidal carbon dioxide (PE'(CO(2))) and mean arterial pressure were measured throughout the study. Anaesthesia was induced with propofol and was maintained with desflurane at end-tidal concentrations of 7.4% (1 MAC) or 10.8% (1.5 MAC). The order of administration of the desflurane concentrations was determined randomly and a period of 15 min was allowed for equilibration at each concentration. The transient hyperaemic response tests were performed before induction of anaesthesia and after equilibration with each concentration of desflurane. An infusion of phenylephrine was used to maintain pre-induction mean arterial pressure and ventilation was adjusted to maintain the pre-induction value of PE'(CO(2)) throughout the study. Two indices derived from the transient hyperaemic response test (the transient hyperaemic response ratio and the strength of autoregulation) were used to assess cerebral autoregulation. Desflurane resulted in a marked and significant impairment in cerebral autoregulation; at concentrations of 1.5 MAC, autoregulation was almost abolished.

  8. Effects of methacholine infusion on desflurane pharmacokinetics in piglets

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    Alf Kozian

    2015-12-01

    We measured airway pressures, pulmonary resistance, and mean paO2 as well as hemodynamic variables in all pigs before desflurane application and at plateau in both healthy state and during methacholine administration by infusion. By MIGET, fractional alveolar ventilation and pulmonary perfusion in relation to the V.A/Q. compartments, data of logSDQ̇ and logSDV̇ (the second moments describing global dispersion, i.e. heterogeneity of distribution were estimated prior to and after MCh infusion. The uptake and elimination of desflurane was determined by MMIMS.

  9. Pim1 kinase protects airway epithelial cells from cigarette smoke-induced damage and airway inflammation

    NARCIS (Netherlands)

    de Vries, M.; Heijink, Hilde; Gras, R.; den Boef, L. E.; Reinders-Luinge, M.; Pouwels, S. D.; Hylkema, Machteld; van der Toorn, Marco; Brouwer, U.; van Oosterhout, A. J. M.; Nawijn, M. C.

    2014-01-01

    Exposure to cigarette smoke (CS) is the main risk factor for developing chronic obstructive pulmonary disease and can induce airway epithelial cell damage, innate immune responses, and airway inflammation. We hypothesized that cell survival factors might decrease the sensitivity of airway epithelial

  10. Allergen-induced changes in airway responsiveness are related to baseline airway responsiveness

    NARCIS (Netherlands)

    deBruinWeller, MS; Weller, FR; RijssenbeekNouwens, LHM; Jansen, HM; deMonchy, JGR

    1996-01-01

    In the literature, bronchial allergen challenge is usually reported to result in an increase in histamine-induced airway responsiveness (AR). The present study investigated the relation between baseline AR and allergen-induced changes in AR. The effect of allergen challenge on AR was investigated in

  11. Allergen-induced changes in airway responsiveness are related to baseline airway responsiveness

    NARCIS (Netherlands)

    deBruinWeller, MS; Weller, FR; RijssenbeekNouwens, LHM; Jansen, HM; deMonchy, JGR

    1996-01-01

    In the literature, bronchial allergen challenge is usually reported to result in an increase in histamine-induced airway responsiveness (AR). The present study investigated the relation between baseline AR and allergen-induced changes in AR. The effect of allergen challenge on AR was investigated in

  12. Allergen-induced changes in airway responsiveness are related to baseline airway responsiveness

    NARCIS (Netherlands)

    deBruinWeller, MS; Weller, FR; RijssenbeekNouwens, LHM; Jansen, HM; deMonchy, JGR

    In the literature, bronchial allergen challenge is usually reported to result in an increase in histamine-induced airway responsiveness (AR). The present study investigated the relation between baseline AR and allergen-induced changes in AR. The effect of allergen challenge on AR was investigated in

  13. Wogonin Induces Eosinophil Apoptosis and Attenuates Allergic Airway Inflammation

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    Dorward, David A.; Sharma, Sidharth; Rennie, Jillian; Felton, Jennifer M.; Alessandri, Ana L.; Duffin, Rodger; Schwarze, Jurgen; Haslett, Christopher; Rossi, Adriano G.

    2015-01-01

    Rationale: Eosinophils are key effector cells in allergic diseases, including allergic rhinitis, eczema, and asthma. Their tissue presence is regulated by both recruitment and increased longevity at inflamed sites. Objectives: To investigate the ability of the flavone wogonin to induce eosinophil apoptosis in vitro and attenuate eosinophil-dominant allergic inflammation in vivo in mice. Methods: Human and mouse eosinophil apoptosis in response to wogonin was investigated by cellular morphology, flow cytometry, mitochondrial membrane permeability, and pharmacological caspase inhibition. Allergic lung inflammation was modeled in mice sensitized and challenged with ovalbumin. Bronchoalveolar lavage (BAL) and lung tissue were examined for inflammation, mucus production, and inflammatory mediator production. Airway hyperresponsiveness to aerosolized methacholine was measured. Measurements and Main Results: Wogonin induced time- and concentration-dependent human and mouse eosinophil apoptosis in vitro. Wogonin-induced eosinophil apoptosis occurred with activation of caspase-3 and was inhibited by pharmacological caspase inhibition. Wogonin administration attenuated allergic airway inflammation in vivo with reductions in BAL and interstitial eosinophil numbers, increased eosinophil apoptosis, reduced airway mucus production, and attenuated airway hyperresponsiveness. This wogonin-induced reduction in allergic airway inflammation was prevented by concurrent caspase inhibition in vivo. Conclusions: Wogonin induces eosinophil apoptosis and attenuates allergic airway inflammation, suggesting that it has therapeutic potential for the treatment of allergic inflammation in humans. PMID:25629436

  14. Clinical experience with desflurane for paediatric anaesthesia outside the operating room.

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    Alonso, M; Builes, L; Morán, P; Ortega, A; Fernández, E; Reinoso-Barbero, F

    2017-01-01

    Desflurane has been used in paediatric patients for several surgical indications. This article analyses the efficacy and safety of desflurane for diagnostic-therapeutic procedures in remote areas far from operating room in a group of selected patients with no known associated respiratory disease. A retrospective analysis was performed on 2,072 general anaesthesia procedures stored in a computer database, in which desflurane was used in a Paediatric Pain Unit during the years 2013 and 2014. An analysis was also performed using the patient demographics, type of procedure, anaesthetic technique, type of airway management, patient cooperation, and incidence of anaesthetic complications. The study included 876 patients, with a mean age of 8.8 years. The main procedures were bone marrow aspirates (23%), lumbar punctures (20%), panendoscopies (15%), and colonoscopies (5%). Induction was intravenous with propofol (26%) or inhalation with sevoflurane in the remaining 74%. Maintenance consisted of remifentanil and desflurane at mean end tidal concentrations of 6.2±2.1%. The airway was managed through a nasal cannula or face mask in spontaneous ventilation. The effectiveness was 98%, and the incidence of side effects was 15%, which included agitation (6%), headache (4%), nausea-vomiting (3%), and laryngospasm (2%). The maintenance with desflurane (at concentrations close to the hypnotic-MAC in spontaneous ventilation) was effective, with a rapid recovery, and with a low incidence of adverse effects. Copyright © 2016 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Publicado por Elsevier España, S.L.U. All rights reserved.

  15. Eosinophils induce airway smooth muscle cell proliferation.

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    Halwani, Rabih; Vazquez-Tello, Alejandro; Sumi, Yuki; Pureza, Mary Angeline; Bahammam, Ahmed; Al-Jahdali, Hamdan; Soussi-Gounni, Abdelillah; Mahboub, Bassam; Al-Muhsen, Saleh; Hamid, Qutayba

    2013-04-01

    Asthma is characterized by eosinophilic airway inflammation and remodeling of the airway wall. Features of airway remodeling include increased airway smooth muscle (ASM) mass. However, little is known about the interaction between inflammatory eosinophils and ASM cells. In this study, we investigated the effect of eosinophils on ASM cell proliferation. Eosinophils were isolated from peripheral blood of mild asthmatics and non-asthmatic subjects and co-cultured with human primary ASM cells. ASM proliferation was estimated using Ki-67 expression assay. The expression of extracellular matrix (ECM) mRNA in ASM cells was measured using quantitative real-time PCR. The role of eosinophil derived Cysteinyl Leukotrienes (CysLTs) in enhancing ASM proliferation was estimated by measuring the release of leukotrienes from eosinophils upon their direct contact with ASM cells using ELISA. This role was confirmed either by blocking eosinophil-ASM contact or co-culturing them in the presence of leukotrienes antagonist. ASM cells co-cultured with eosinophils, isolated from asthmatics, but not non-asthmatics, had a significantly higher rate of proliferation compared to controls. This increase in ASM proliferation was independent of their release of ECM proteins but dependent upon eosinophils release of CysLTs. Eosinophil-ASM cell to cell contact was required for CysLTs release. Preventing eosinophil contact with ASM cells using anti-adhesion molecules antibodies, or blocking the activity of eosinophil derived CysLTs using montelukast inhibited ASM proliferation. Our results indicated that eosinophils contribute to airway remodeling during asthma by enhancing ASM cell proliferation and hence increasing ASM mass. Direct contact of eosinophils with ASM cells triggers their release of CysLTs which enhance ASM proliferation. Eosinophils, and their binding to ASM cells, constitute a potential therapeutic target to interfere with the series of biological events leading to airway remodeling

  16. The Effect of Desflurane on Neuronal Communication at a Central Synapse

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    Mapelli, Jonathan; Gandolfi, Daniela; Giuliani, Enrico; Prencipe, Francesco P.; Pellati, Federica; Barbieri, Alberto; D’Angelo, Egidio; Bigiani, Albertino

    2015-01-01

    Although general anesthetics are thought to modify critical neuronal functions, their impact on neuronal communication has been poorly examined. We have investigated the effect induced by desflurane, a clinically used general anesthetic, on information transfer at the synapse between mossy fibers and granule cells of cerebellum, where this analysis can be carried out extensively. Mutual information values were assessed by measuring the variability of postsynaptic output in relationship to the variability of a given set of presynaptic inputs. Desflurane synchronized granule cell firing and reduced mutual information in response to physiologically relevant mossy fibers patterns. The decrease in spike variability was due to an increased postsynaptic membrane excitability, which made granule cells more prone to elicit action potentials, and to a strengthened synaptic inhibition, which markedly hampered membrane depolarization. These concomitant actions on granule cells firing indicate that desflurane re-shapes the transfer of information between neurons by providing a less informative neurotransmission rather than completely silencing neuronal activity. PMID:25849222

  17. Electroencephalographic effect of age-adjusted 1 MAC desflurane and sevoflurane in young, middle-aged, and elderly patients.

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    Kanazawa, Shinya; Oda, Yutaka; Maeda, Chika; Okutani, Ryu

    2017-08-08

    We examined the hypothesis that 1 minimum alveolar concentration (MAC) of desflurane and sevoflurane provides different depth of anesthesia. One hundred and twenty young (20-30 years), middle-aged (31-65 years), and elderly (66-80 years) patients were randomly allocated to receive either desflurane or sevoflurane (n = 20, each group). General anesthesia was induced with propofol 2 mg/kg bolus and remifentanil 0.25 µg/kg/min, which was stopped after tracheal intubation. Maintenance of anesthesia was started with an end-tidal concentration of desflurane or sevoflurane at age-adjusted 1 MAC and maintained for 10 min, followed by 1-min assessment of bispectral index (BIS), 95% spectral edge frequency (SEF95), and amplitude of the electroencephalogram taken at 10-s intervals. BIS and SEF95 in patients receiving 1 MAC desflurane were significantly lower than those receiving 1 MAC sevoflurane including all age groups [35 (29, 39) vs. 41 (38, 49); 12.53 (10.99, 13.95) Hz vs. 14.42 (12.99, 17.17) Hz median (25, 75 percentile), respectively, P MAC desflurane than those receiving 1 MAC sevoflurane, suggesting that desflurane provides higher depth of anesthesia than sevoflurane at 1 MAC.

  18. Effects of Flavin7 on allergen induced hyperreactivity of airways

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    Franova S

    2009-12-01

    Full Text Available Abstract Some studies have suggested that the polyphenolic compounds might reduce the occurrence of asthma symptoms. The aim of our experiments was to evaluate the effects of 21 days of the flavonoid Flavin7 administration on experimentally induced airway inflammation in ovalbumin-sensitized guinea pigs. We assessed tracheal smooth muscle reactivity by an in vitro muscle-strip method; changes in airway resistance by an in vivo plethysmographic method; histological picture of tracheal tissue; and the levels of interleukin 4 (IL-4, and interleukin 5 (IL-5 in bronchoalveolar lavage fluid (BALF. Histological investigation of tracheal tissue and the concentrations of the inflammatory cytokines IL-4 and IL-5 in BALF were used as indices of airway inflammation. Administration of Flavin7 caused a significant decrease of specific airway resistance after histamine nebulization and a decline in tracheal smooth muscle contraction amplitude in response to bronchoconstricting mediators. Flavin7 minimized the degree of inflammation estimated on the basis of eosinophil calculation and IL-4 and IL-5 concentrations. In conclusion, administration of Flavin7 showed bronchodilating and anti-inflammatory effects on allergen-induced airway inflammation.

  19. Endotoxin Is Not Essential for the Development of Cockroach Induced Allergic Airway Inflammation

    OpenAIRE

    2012-01-01

    Purpose Cockroach (CR) is an important inhalant allergen and can induce allergic asthma. However, the mechanism by which CR induces airway allergic inflammation and the role of endotoxin in CR extract are not clearly understood in regards to the development of airway inflammation. In this study, we evaluated whether endotoxin is essential to the development of CR induced airway allergic inflammation in mice. Materials and Methods Airway allergic inflammation was induced by intranasal administ...

  20. Deficiency of nitric oxide in polycation-induced airway hyperreactivity

    NARCIS (Netherlands)

    Meurs, Herman; Schuurman, F.E; Duyvendak, M; Zaagsma, Hans

    1999-01-01

    Using a perfused guinea-pig tracheal tube preparation, we investigated the role of endogenous nitric oxide (NO) in polycation-induced airway hyperreactivity (AHR) to methacholine. Intraluminal (IL) administration of the NO synthase inhibitor N-omega-nitro-L-arginine methyl ester (L-NAME; 100 mu M) c

  1. Angiogenesis is induced by airway smooth muscle strain.

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    Hasaneen, Nadia A; Zucker, Stanley; Lin, Richard Z; Vaday, Gayle G; Panettieri, Reynold A; Foda, Hussein D

    2007-10-01

    Angiogenesis is an important feature of airway remodeling in both chronic asthma and chronic obstructive pulmonary disease (COPD). Airways in those conditions are exposed to excessive mechanical strain during periods of acute exacerbations. We recently reported that mechanical strain of human airway smooth muscle (HASM) led to an increase in their proliferation and migration. Sustained growth in airway smooth muscle in vivo requires an increase in the nutritional supply to these muscles, hence angiogenesis. In this study, we examined the hypothesis that cyclic mechanical strain of HASM produces factors promoting angiogenic events in the surrounding vascular endothelial cells. Our results show: 1) a significant increase in human lung microvascular endothelial cell (HMVEC-L) proliferation, migration, and tube formation following incubation in conditioned media (CM) from HASM cells exposed to mechanical strain; 2) mechanical strain of HASM cells induced VEGF expression and release; 3) VEGF neutralizing antibodies inhibited the proliferation, migration, and tube formations of HMVEC-L induced by the strained airway smooth muscle CM; 4) mechanical strain of HASM induced a significant increase in hypoxia-inducible factor-1alpha (HIF-1alpha) mRNA and protein, a transcription factor required for VEGF gene transcription; and 5) mechanical strain of HASM induced HIF-1alpha/VEGF through dual phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) and ERK pathways. In conclusion, exposing HASM cells to mechanical strain induces signal transduction pathway through PI3K/Akt/mTOR and ERK pathways that lead to an increase in HIF-1alpha, a transcription factor required for VEGF expression. VEGF release by mechanical strain of HASM may contribute to the angiogenesis seen with repeated exacerbation of asthma and COPD.

  2. 末梢灌注指数监测地氟醚诱发患者交感神经兴奋的评价%Evaluation of desflurane-induced sympathetic activation with finger tip perfusion index

    Institute of Scientific and Technical Information of China (English)

    沙勤; 薛庆生; 张维光; 于布为

    2008-01-01

    目的 评价末梢灌注指数(TPI)监测地氟醚诱发的患者交感神经兴奋作用.方法 择期全麻患者48例,年龄25~60岁,ASA Ⅰ或Ⅱ级,随机分为3组(n=16):七氟醚组(Ⅰ组)、地氟醚组(Ⅱ组)和地氟醚+异丙酚组(Ⅲ组).气管插管后Ⅰ组和Ⅱ组地氟醚或七氟醚呼气末浓度依次快速达到0.5 MAC、1.0 MAC和1.5 MAC,并在每个水平维持5 min.Ⅲ组在气管插管后靶控输注异丙酚.血浆靶浓度至1μg/ml,地氟醚呼气末浓度依次快速达到0.5 MAC、1.0 MAC,并在每个水平维持5 min.分别在给予咪达唑仑后5 min(T0)、麻醉诱导后3 min(T1)、插管后即刻(T2)、呼气末浓度达到0.5 MAC(T3)、0.5 MAC后5 min(T4)、1.0 MAC(T5)、1.0MAC后5min(T6)、1.5MAC(T7)、1.5MAC后5min(T8)时记录心率(HR)、平均动脉压(MAP)、TPI、脑电双频谱指数,并在T0、T1、T2、T5、T7时测定血浆肾素活性和血管紧张素Ⅱ水平.结果 与T4时比较,Ⅱ组T5时,IPI降低(P<0.05);与T7时比较,Ⅱ组T4~6、T8时HR、MAP降低,T3~6、T8时TPI降低(P<0.05);与Ⅰ组比较,Ⅱ组T7时HR、MAP升高,TPI降低(P<0.05);Ⅱ组T5和T7时TPI出现变化最大值的时间短于HR、MAP;ATPI与△HR、AMAP呈负相关(r=-0.593,P<0.05;r=-0.591,P<0.05);与Ⅰ组比较,Ⅱ组血浆肾素活性和AT-Ⅱ浓度升高(P<0.05).结论 TPI可灵敏地反映地氟醚诱发的患者交感神经兴奋.%Objective To evaluate the desflurane-induced sympathetic activation with finger tip perfusion index (FTPl). Methods Forty-eight ASA ⅠorⅡ patients aged 25-60 yr undergoing elective surgery under general anesthesia were randomly divided into 3 groups (n=16 each): groupⅠsevoflurane; group Ⅱ desflurane and groupⅢ desthrane + propofol. Anesthesia was induced with midazolam 0.03 mg/kg, propofol 2 mg/kg and fentanyl 2 μg/kg. Tracheal intubatian was facilitated with vecuronium 0.1 mg/kg. The patients were mechanically ventilated (VT 8-10 ml/kg, RR 12 bpm). PETCO2 was maintained at 35-40 mm Hg. In

  3. Focal adhesion kinase regulates collagen I-induced airway smooth muscle phenotype switching

    NARCIS (Netherlands)

    Dekkers, Bart G J; Spanjer, Anita I R; van der Schuyt, Robert D; Kuik, Willem Jan; Zaagsma, Johan; Meurs, Herman

    2013-01-01

    Increased extracellular matrix (ECM) deposition and airway smooth muscle (ASM) mass are major contributors to airway remodeling in asthma. Recently, we demonstrated that the ECM protein collagen I, which is increased surrounding asthmatic ASM, induces a proliferative, hypocontractile ASM phenotype.

  4. Chronic respiratory aeroallergen exposure in mice induces epithelial-mesenchymal transition in the large airways.

    Directory of Open Access Journals (Sweden)

    Jill R Johnson

    Full Text Available Chronic allergic asthma is characterized by Th2-polarized inflammation and leads to airway remodeling and fibrosis but the mechanisms involved are not clear. To determine whether epithelial-mesenchymal transition contributes to airway remodeling in asthma, we induced allergic airway inflammation in mice by intranasal administration of house dust mite (HDM extract for up to 15 consecutive weeks. We report that respiratory exposure to HDM led to significant airway inflammation and thickening of the smooth muscle layer in the wall of the large airways. Transforming growth factor beta-1 (TGF-β1 levels increased in mouse airways while epithelial cells lost expression of E-cadherin and occludin and gained expression of the mesenchymal proteins vimentin, alpha-smooth muscle actin (α-SMA and pro-collagen I. We also observed increased expression and nuclear translocation of Snail1, a transcriptional repressor of E-cadherin and a potent inducer of EMT, in the airway epithelial cells of HDM-exposed mice. Furthermore, fate-mapping studies revealed migration of airway epithelial cells into the sub-epithelial regions of the airway wall. These results show the contribution of EMT to airway remodeling in chronic asthma-like inflammation and suggest that Th2-polarized airway inflammation can trigger invasion of epithelial cells into the subepithelial regions of the airway wall where they contribute to fibrosis, demonstrating a previously unknown plasticity of the airway epithelium in allergic airway disease.

  5. Effects of 1 MAC desflurane on cerebral metabolism, blood flow and carbon dioxide reactivity in humans.

    Science.gov (United States)

    Mielck, F; Stephan, H; Buhre, W; Weyland, A; Sonntag, H

    1998-08-01

    We investigated the cerebral haemodynamic effects of 1 MAC desflurane anaesthesia in nine male patients scheduled for elective coronary bypass grafting. For the measurement of cerebral blood flow (CBF) a modified Kety-Schmidt saturation technique with argon as inert tracer gas was used. Measurements of CBF were made before induction of anaesthesia and 30 min after induction under normocapnic, hypocapnic and hypercapnic conditions in sequence. Changes in mean arterial pressure after induction of anaesthesia and during the course of the study were minimized using norepinephrine infusion. In comparison with the awake state under normocapnic conditions, desflurane reduced mean cerebral metabolic rate of oxygen (CMRO2) by 51% and mean cerebral metabolic rate of glucose (CMRglc) by 35%. Concomitantly, CBF was significantly reduced by 22%; jugular venous oxygen saturation (SjvO2) increased from 58 to 74%. Hypo- and hypercapnia caused a 22% decrease and a 178% increase in CBF, respectively. These findings may be interpreted as the result of two opposing mechanisms: cerebral vasoconstriction induced by a reduction of cerebral metabolism and a direct vasodilator effect of desflurane. CBF alterations under variation of PaCO2 indicate that cerebrovascular carbon dioxide reactivity is not impaired by application of 1 MAC desflurane.

  6. Simvastatin attenuates lipopolysaccharide-induced airway mucus hypersecretion in rats

    Institute of Scientific and Technical Information of China (English)

    OU Xue-mei; WANG Bai-ding; WEN Fu-qiang; FENG Yu-lin; HUANG Xiang-yang; XIAO Jun

    2008-01-01

    Background Mucus hypersecretion in the respiratory tract and goblet cell metaplasia in the airway epithelium contribute to the morbidity and mortality associated with airway inflammatory diseases.This study aimed to examine the effect and mechanisms of simvastatin on airway mucus hypersecretion in rats treated with lipopolysaccharide (LPS).Methods Mucus hypersecretion in rat airways was induced by intra-tracheal instillation of LPS.Rats treated with or without LPS were administered intra-peritoneally simvastatin (5 and 20 mg/kg) for 4 days.Expression of Muc5ac,RhoA and mitogen-activated protein kinases (MAPK) p38 in lung were detected by real-time polymerase chain reaction (PCR),immunohistochemistry or Western blotting.Tumor necrosis factor (TNF)-a and IL-8 in bronchoalveolar lavage fluid (BALF)were assayed by an enzyme-linked lectin assay and enzyme linked immunosorbent assay (ELISA).Results Simvastatin attenuated LPS-induced goblet cell hyperplasia in bronchial epithelium and Muc5ac hypersecretion at both the gene and protein levels in lung (P<0.05).Moreover,simvastatin inhibited neutrophil accumulation and the increased concentration of TNF-α and IL-8 in BALF follows LPS stimulation (P<0.05).The higher dose of simvastatin was associated with a more significant reduction in Muc5ac mRNA expression,neutrophil accumulation and inflammatory cytokine release.Simultaneously,the increased expression of RhoA and p38 MAPK were observed in LPS-treated lung (P<0.05).Simvastatin inhibited the expression of RhoA and p38 phosphorylation in lung following LPS stimulation (P<0.05).However,the increased expression of p38 protein in LPS-traated lung was not affected by simvastatin administration.Conclusions Simvastatin attenuates airway mucus hypersecretion and pulmonary inflammatory damage induced by LPS.The inhibitory effect of simvastatin on airway mucus hypersecretion may be through,at least in part,the suppression of neutrophil accumulation and inflammatory cytokine

  7. Desflurane increases heart rate independent of sympathetic activity in dogs.

    Science.gov (United States)

    Picker, O; Schwarte, L A; Schindler, A W; Scheeren, T W L

    2003-12-01

    Desflurane has been shown to increase sympathetic activity and heart rate (HR) in a concentration-dependent manner. Nevertheless, desflurane, like all other volatile anaesthetics, increased HR in parallel to vagal inhibition in a previous study. Therefore, our hypothesis is that desflurane elicits tachycardia by vagal inhibition rather than by activation of the sympathetic nervous system. Six dogs were studied awake and during desflurane anaesthesia (1 and 2 MAC) alone, after pretreatment with propranolol (2 mg kg(-1) followed by 1 mg kg(-1) h(-1)), or after pre-treatment with atropine (0.1 mg kg(-1) followed by 0.05 mg kg(-1) h(-1)). The effects on HR and HR variability were compared by an analysis of variance (P MAC of desflurane from about 60 (awake) to 118 +/- 2 beats min(-1) (mean +/- SEM) in controls and to 106 +/- 3 beats min(-1) in dogs pre-treated with propranolol. In contrast, pretreatment with atropine increased HR from 64 +/- 2 to 147 +/- 5 beats min(-1) (awake) and HR decreased to 120 +/- 5 beats min(-1) after adding desflurane. High-frequency power correlated inversely with HR (r2 = 0.95/0.93) during desflurane alone and in the presence of beta-adrenoceptor blockade, with no significant difference between regression lines. There was no correlation between these variables during atropine/desflurane. The increase in HR elicited by desflurane mainly results from vagal inhibition and not from sympathetic activation.

  8. A Phosphorylatable Sphingosine Analog Induces Airway Smooth Muscle Cytostasis and Reverses Airway Hyperresponsiveness in Experimental Asthma

    Science.gov (United States)

    Gendron, David R.; Lecours, Pascale B.; Lemay, Anne-Marie; Beaulieu, Marie-Josée; Huppé, Carole-Ann; Lee-Gosselin, Audrey; Flamand, Nicolas; Don, Anthony S.; Bissonnette, Élyse; Blanchet, Marie-Renée; Laplante, Mathieu; Bourgoin, Sylvain G.; Bossé, Ynuk; Marsolais, David

    2017-01-01

    In asthma, excessive bronchial narrowing associated with thickening of the airway smooth muscle (ASM) causes respiratory distress. Numerous pharmacological agents prevent experimental airway hyperresponsiveness (AHR) when delivered prophylactically. However, most fail to resolve this feature after disease is instated. Although sphingosine analogs are primarily perceived as immune modulators with the ability to prevent experimental asthma, they also influence processes associated with tissue atrophy, supporting the hypothesis that they could interfere with mechanisms sustaining pre-established AHR. We thus assessed the ability of a sphingosine analog (AAL-R) to reverse AHR in a chronic model of asthma. We dissected the pharmacological mechanism of this class of agents using the non-phosphorylatable chiral isomer AAL-S and the pre-phosphorylated form of AAL-R (AFD-R) in vivo and in human ASM cells. We found that a therapeutic course of AAL-R reversed experimental AHR in the methacholine challenge test, which was not replicated by dexamethasone or the non-phosphorylatable isomer AAL-S. AAL-R efficiently interfered with ASM cell proliferation in vitro, supporting the concept that immunomodulation is not necessary to interfere with cellular mechanisms sustaining AHR. Moreover, the sphingosine-1-phosphate lyase inhibitor SM4 and the sphingosine-1-phosphate receptor antagonist VPC23019 failed to inhibit proliferation, indicating that intracellular accumulation of sphingosine-1-phosphate or interference with cell surface S1P1/S1P3 activation, are not sufficient to induce cytostasis. Potent AAL-R-induced cytostasis specifically related to its ability to induce intracellular AFD-R accumulation. Thus, a sphingosine analog that possesses the ability to be phosphorylated in situ interferes with cellular mechanisms that beget AHR.

  9. Atmospheric chemistry of isoflurane, desflurane, and sevoflurane

    DEFF Research Database (Denmark)

    Andersen, Mads P. Sulbæk; Nielsen, Ole John; Karpichev, Boris

    2012-01-01

    (sevoflurane) are estimated at 3.2, 14, and 1.1 years, respectively. The 100 year time horizon global warming potentials of isoflurane, desflurane, and sevoflurane are 510, 2540, and 130, respectively. The atmospheric degradation products of these anesthetics are not of environmental concern.......The smog chamber/Fourier-transform infrared spectroscopy (FTIR) technique was used to measure the rate coefficients k(Cl + CF(3)CHClOCHF(2), isoflurane) = (4.5 ± 0.8) × 10(-15), k(Cl + CF(3)CHFOCHF(2), desflurane) = (1.0 ± 0.3) × 10(-15), k(Cl + (CF(3))(2)CHOCH(2)F, sevoflurane) = (1.1 ± 0.1) × 10...

  10. Acid aspiration-induced airways hyperresponsiveness in mice.

    Science.gov (United States)

    Allen, Gilman B; Leclair, Timothy R; von Reyn, Jessica; Larrabee, Yuna C; Cloutier, Mary E; Irvin, Charles G; Bates, Jason H T

    2009-12-01

    The role of gastroesophageal reflux and micro-aspiration as a trigger of airways hyperresponsiveness (AHR) in patients with asthma is controversial. The role of acid reflux and aspiration as a direct cause of AHR in normal subjects is also unclear. We speculated that aspiration of a weak acid with a pH (1.8) equivalent to the upper range of typical gastric contents would lead to AHR in naive mice. We further speculated that modest reductions in aspirate acidity to a level expected during gastric acid suppression therapy (pH 4.0) would impede aspiration-induced AHR. BALB/c female mice were briefly anesthetized with isoflurane and allowed to aspirate 75 microl of saline with HCl (pH 1.8, 4.0, or 7.4) or underwent sham aspiration. Mice were re-anesthetized 2 or 24 h later, underwent tracheostomy, and were coupled to a mechanical ventilator. Forced oscillations were used to periodically measure respiratory impedance (Zrs) following aerosol delivery of saline and increasing doses of methacholine to measure for AHR. Values for elastance (H), airways resistance (R(N)), and tissue damping (G) were derived from Zrs. Aspirate pH of 1.8 led to a significant overall increase in peak R(N), G, and H compared with pH 4.0 and 7.4 at 2 and 24 h. Differences between pH 7.4 and 4.0 were not significant. In mice aspirating pH 1.8 compared with controls, airway lavage fluid contained more neutrophils, higher protein, and demonstrated higher permeability. We conclude that acid aspiration triggers an acute AHR, driven principally by breakdown of epithelial barrier integrity within the airways.

  11. Cerebral blood flow at 0.5 and 1.0 minimal alveolar concentrations of desflurane or sevoflurane compared with isoflurane in normoventilated pigs.

    Science.gov (United States)

    Holmström, A; Akeson, J

    2003-04-01

    Whether desflurane and sevoflurane have clinical advantages over isoflurane in neuroanesthesia is much debated. A porcine model was used for comparison of desflurane and sevoflurane with isoflurane with respect to their cerebrovascular effects. The minimal alveolar concentration (MAC) of each of the three agents was first determined in a standardized manner in six domestic juvenile pigs to enhance comparison reliability. Six other pigs were then anesthetized with isoflurane, desflurane, and sevoflurane, given in sequence to each pig in an even crosswise order with the first agent also used to maintain anesthesia during surgical preparation. Cerebral blood flow (CBF) was calculated from the clearance curve of intraarterially injected 133Xe. The mean arterial pressure (MAP) was invasively monitored. The estimated cerebrovascular resistance (CVRe) was calculated by dividing MAP with CBF, thereby approximating the cerebral perfusion pressure with MAP. For both MAC levels, the trend for CBF was desflurane > isoflurane > sevoflurane, and the trend for MAP and CVRe was sevoflurane > isoflurane > desflurane. Statistical comparison of desflurane and sevoflurane with isoflurane with respect to CBF and MAP revealed two statistically significant differences-namely, that CBF at 1.0 MAC desflurane was 17% higher than CBF at 1.0 MAC isoflurane (P =.0025) and that MAP at 1.0 MAC sevoflurane was 16% higher than MAP at 1.0 MAC isoflurane (P =.011). Consequently, in this study at normocapnia, these agents did not seem to differ much in their cerebral vasodilating effects at lower doses. At higher doses, however, desflurane, in contrast to sevoflurane, was found to induce more cerebral vasodilation than isoflurane.

  12. Haemodynamic changes during halothane, sevoflurane and desflurane anaesthesia in dogs before and after the induction of severe heart failure.

    Science.gov (United States)

    Preckel, B; Müllenheim, J; Hoff, J; Obal, D; Heiderhoff, M; Thämer, V; Schlack, W

    2004-10-01

    The effects of desflurane and sevoflurane on the failing myocardium are still uncertain. We investigated the effects of different concentrations of sevoflurane, desflurane and halothane in dogs with pacing induced chronic heart failure. Global (left ventricular pressure, left ventricular dP/dt, Konigsbergtransducer) and regional myocardial function (systolic segment length shortening, ultrasonic crystals) were measured in chronically instrumented dogs with tachycardia induced severe congestive heart failure. Measurements were performed in healthy dogs and after induction of heart failure in the awake state and during anaesthesia with 0.75, 1.0, 1.25 and 1.75 minimum alveolar concentration (MAC) of halothane, sevoflurane or desflurane. The anaesthetics reduced dP/dtmax in a dose-dependent manner in healthy dogs (dP/dtmax decreased to 43-53% of awake values at 1.75 MAC). Chronic rapid left ventricular pacing increased heart rate and left ventricular end-diastolic pressure and decreased mean arterial pressure, left ventricular systolic pressure and dP/dtmax. The reduction in contractility was similar in the failing myocardium (to 41-50% of awake values at 1.75 MAC). Segmental shortening was reduced during anaesthesia by 50-62% after pacing compared with 22-44% in normal hearts. While there were similar effects of the different anaesthetics on diastolic function in healthy dogs, after induction of heart failure a more pronounced increase of the time constant of isovolumic relaxation and a greater decrease of dP/dtmin was observed with sevoflurane than with desflurane, indicating a stronger depression of diastolic function. While the negative inotropic effects of sevoflurane and desflurane were similar in normal and in the failing myocardium in vivo, desflurane led to a better preservation of diastolic function in the failing myocardium.

  13. Stimulation of cannabinoid CB1 receptors prevents nerve-mediated airway hyperreactivity in NGF-induced inflammation in mouse airways.

    Science.gov (United States)

    Bozkurt, Turgut Emrah; Larsson, Olivia; Adner, Mikael

    2016-04-05

    Cannabinoids are known to inhibit neuronal activity and have significant immunomodulatory effects which suggest a role in inflammatory airway diseases. In the present study, we tested the hypothesis that cannabinoids have both acute and chronic modulatory effects on nerve-mediated contractions in NGF-induced airway inflammation. Contractions induced by electrical field stimulation (EFS) were examined in tracheal segments isolated from male BALB/c mice. Tissues were both used fresh or after four days of culture with NGF to induce airway inflammation, and further exposed to cannabinoid receptor agonists. In order to evaluate nerve density, tracheal segments were also examined by immunohistochemistry after in vitro treatments. The CB1 receptor agonists ACEA and ACPA inhibited the constant train EFS-induced contractions in both fresh and NGF-exposed tracheas, an effect that could be blocked by the CB1 receptor antagonist AM251. Culturing the tissues with NGF up-regulated the frequency-dependent EFS-contractions in isolated tracheas. This up-regulation could be inhibited by concomitant treatment with ACEA or ACPA. The treatment with NGF and/or ACEA did not affect the potency or the maximum response to carbachol. In histological sections, it was recognized that the enhanced effect induced by NGF was associated with an increase in nerve density, which, similarly, could be prevented by ACEA treatment. This study shows that stimulation of cannabinoid CB1 receptors modifies the increase of neuronal activity and density in NGF-induced airway inflammation and directly inhibits cholinergic contractions in the airways by a presynaptic mechanism. These findings indicate a protective role of CB1 receptors in airway inflammation.

  14. Comparative evaluation of propofol, sevoflurane and desflurane for neuroanaesthesia: A prospective randomised study in patients undergoing elective supratentorial craniotomy

    Science.gov (United States)

    Bastola, Priska; Bhagat, Hemant; Wig, Jyotsna

    2015-01-01

    Background and Aims: Both inhalational and intravenous anaesthetic agents are being used for neuroanaesthesia. Clinical trials comparing “propofol and sevoflurane” and “desflurane and sevoflurane” have been published. However, the comparison of all the three anaesthetics in neurosurgical patients has not been done. A randomised clinical study was carried out comparing propofol, sevoflurane and desflurane to find the ideal neuroanaesthetic agent. Methods: A total of 75 adult patients undergoing elective craniotomy for supratentorial tumours were included in the study. The patients were induced with morphine 0.1 mg/kg and thiopentone 4-6 mg/kg. Neuromuscular blockade was facilitated with vecuronium. The patients were randomised to receive propofol, sevoflurane or desflurane along with nitrous oxide in oxygen for maintenance of anaesthesia. The neuromuscular blockade was reversed following the surgery once the patients opened eyes or responded to verbal commands. The three anaesthetics were compared for their effects on haemodynamics, brain relaxation and emergence characteristics. Results: The mean arterial blood pressure during anaesthesia was comparable among the groups. The patients receiving sevoflurane had faster heart rates intraoperatively when compared to desflurane (P 0.05). The time to response to verbal commands were significantly prolonged with use of sevoflurane (8.0 ± 2.9 min) when compared to propofol (5.3 ± 2.9 min) and desflurane (5.2 ± 2.6 min) (P = 0.003). However, the time to emergence and the number of patients who had early emergence ( 0.05). The quality of emergence (coughing and emergence agitation), as well as postoperative complications, were also comparable among the three groups. Conclusions: All the three anaesthetic agents-propofol, sevoflurane and desflurane appear comparable and acceptable with regard to their clinical profile during anaesthesia in patients undergoing elective supratentorial surgeries. PMID:26019353

  15. Comparative evaluation of propofol, sevoflurane and desflurane for neuroanaesthesia: A prospective randomised study in patients undergoing elective supratentorial craniotomy

    Directory of Open Access Journals (Sweden)

    Priska Bastola

    2015-01-01

    Full Text Available Background and Aims: Both inhalational and intravenous anaesthetic agents are being used for neuroanaesthesia. Clinical trials comparing "propofol and sevoflurane" and "desflurane and sevoflurane" have been published. However, the comparison of all the three anaesthetics in neurosurgical patients has not been done. A randomised clinical study was carried out comparing propofol, sevoflurane and desflurane to find the ideal neuroanaesthetic agent. Methods: A total of 75 adult patients undergoing elective craniotomy for supratentorial tumours were included in the study. The patients were induced with morphine 0.1 mg/kg and thiopentone 4-6 mg/kg. Neuromuscular blockade was facilitated with vecuronium. The patients were randomised to receive propofol, sevoflurane or desflurane along with nitrous oxide in oxygen for maintenance of anaesthesia. The neuromuscular blockade was reversed following the surgery once the patients opened eyes or responded to verbal commands. The three anaesthetics were compared for their effects on haemodynamics, brain relaxation and emergence characteristics. Results: The mean arterial blood pressure during anaesthesia was comparable among the groups. The patients receiving sevoflurane had faster heart rates intraoperatively when compared to desflurane (P 0.05. The time to response to verbal commands were significantly prolonged with use of sevoflurane (8.0 ± 2.9 min when compared to propofol (5.3 ± 2.9 min and desflurane (5.2 ± 2.6 min (P = 0.003. However, the time to emergence and the number of patients who had early emergence ( 0.05. The quality of emergence (coughing and emergence agitation, as well as postoperative complications, were also comparable among the three groups. Conclusions: All the three anaesthetic agents-propofol, sevoflurane and desflurane appear comparable and acceptable with regard to their clinical profile during anaesthesia in patients undergoing elective supratentorial surgeries.

  16. TIM-3 is not essential for development of airway inflammation induced by house dust mite antigens

    Directory of Open Access Journals (Sweden)

    Yoshihisa Hiraishi

    2016-10-01

    Conclusions: Our findings indicate that, in mice, TIM-3 is not essential for development of HDM-induced acute or chronic allergic airway inflammation, although it appears to be involved in reduced lymphocyte recruitment during HDM-induced chronic allergic airway inflammation.

  17. Effects of 4 months of smoking in mice with ovalbumin-induced airway inflammation

    NARCIS (Netherlands)

    Melgert, B. N.; Timens, W.; Kerstjens, H. A.; Geerlings, M.; Luinge, M. A.; Schouten, J. P.; Postma, D. S.; Hylkema, M. N.

    2007-01-01

    Background The effects of smoking on asthma pathogenesis are complex and not well studied. We have shown recently that 3 weeks of smoking attenuates ovalbumin (OVA)-induced airway inflammation in mice and that 4-6 months of smoking induces emphysema in mice without airway inflammation. Effects of co

  18. Picornavirus-Induced Airway Mucosa Immune Profile in Asymptomatic Neonates

    DEFF Research Database (Denmark)

    Wolsk, Helene M.; Følsgaard, Nilofar V.; Birch, Sune;

    2016-01-01

    Bacterial airway colonization is known to alter the airway mucosa immune response in neonates whereas the impact of viruses is unknown. The objective was therefore to examine the effect of respiratory viruses on the immune signature in the airways of asymptomatic neonates. Nasal aspirates from 571...

  19. Salvinorin A Inhibits Airway Hyperreactivity Induced by Ovalbumin Sensitization

    Science.gov (United States)

    Rossi, Antonietta; Caiazzo, Elisabetta; Bilancia, Rossella; Riemma, Maria A.; Pagano, Ester; Cicala, Carla; Ialenti, Armando; Zjawiony, Jordan K.; Izzo, Angelo A.; Capasso, Raffaele; Roviezzo, Fiorentina

    2017-01-01

    Salvinorin A, a neoclerodane diterpene isolated from Salvia divinorum, exerts a number of pharmacological actions which are not solely limited to the central nervous system. Recently it has been demonstrated that Salvinorin A inhibits acute inflammatory response affecting leukotriene (LT) production. Since LTs are potent lipid mediators implicated in allergic diseases, we evaluated the effect of Salvinorin A on allergic inflammation and on airways following sensitization in the mouse. Mice were sensitized with s.c. injection of ovalbumin (OVA) on days 1 and 8. Sensitized mice received on days 9 and 12 on the shaved dorsal surface air administration to induce the development of the air-pouches. On day 15 animals were challenged by injection of OVA into the air-pouch. Salvinorin A, administered (10 mg/kg) before each allergen exposure, significantly reduced OVA-induced LT increase in the air pouch. This effect was coupled to a reduction in cell recruitment and Th2 cytokine production. In another set of experiments, mice were sensitized with OVA and both bronchial reactivity and pulmonary inflammation were assessed. Salvinorin A abrogated bronchial hyperreactivity and interleukin (IL)-13 production, without effect on pulmonary inflammation. Indeed cell infiltration and peribronchial edema were still present following diterpenoid treatment. Similarly, pulmonary IL-4 and plasmatic IgE levels were not modulated. Conversely, Salvinorin A significantly reduced LTC4 production in the lung of sensitized mice. Finally mast cell activity was evaluated by means of toluidine blue staining. Data obtained evidenced that Salvinorin A significantly inhibited mast cell degranulation in the lung. Our study demonstrates that Salvinorin A inhibits airway hyperreactivity induced by sensitization by inhibition of LT production and mast cell degranulation. In conclusion Salvinorin A could represent a promising candidate for drug development in allergic diseases such as asthma. PMID

  20. Salvinorin A Inhibits Airway Hyperreactivity Induced by Ovalbumin Sensitization.

    Science.gov (United States)

    Rossi, Antonietta; Caiazzo, Elisabetta; Bilancia, Rossella; Riemma, Maria A; Pagano, Ester; Cicala, Carla; Ialenti, Armando; Zjawiony, Jordan K; Izzo, Angelo A; Capasso, Raffaele; Roviezzo, Fiorentina

    2016-01-01

    Salvinorin A, a neoclerodane diterpene isolated from Salvia divinorum, exerts a number of pharmacological actions which are not solely limited to the central nervous system. Recently it has been demonstrated that Salvinorin A inhibits acute inflammatory response affecting leukotriene (LT) production. Since LTs are potent lipid mediators implicated in allergic diseases, we evaluated the effect of Salvinorin A on allergic inflammation and on airways following sensitization in the mouse. Mice were sensitized with s.c. injection of ovalbumin (OVA) on days 1 and 8. Sensitized mice received on days 9 and 12 on the shaved dorsal surface air administration to induce the development of the air-pouches. On day 15 animals were challenged by injection of OVA into the air-pouch. Salvinorin A, administered (10 mg/kg) before each allergen exposure, significantly reduced OVA-induced LT increase in the air pouch. This effect was coupled to a reduction in cell recruitment and Th2 cytokine production. In another set of experiments, mice were sensitized with OVA and both bronchial reactivity and pulmonary inflammation were assessed. Salvinorin A abrogated bronchial hyperreactivity and interleukin (IL)-13 production, without effect on pulmonary inflammation. Indeed cell infiltration and peribronchial edema were still present following diterpenoid treatment. Similarly, pulmonary IL-4 and plasmatic IgE levels were not modulated. Conversely, Salvinorin A significantly reduced LTC4 production in the lung of sensitized mice. Finally mast cell activity was evaluated by means of toluidine blue staining. Data obtained evidenced that Salvinorin A significantly inhibited mast cell degranulation in the lung. Our study demonstrates that Salvinorin A inhibits airway hyperreactivity induced by sensitization by inhibition of LT production and mast cell degranulation. In conclusion Salvinorin A could represent a promising candidate for drug development in allergic diseases such as asthma.

  1. Chitin-Induced Airway Epithelial Cell Innate Immune Responses Are Inhibited by Carvacrol/Thymol

    OpenAIRE

    Ali Reza Khosravi; David J Erle

    2016-01-01

    Chitin is produced in large amounts by fungi, insects, and other organisms and has been implicated in the pathogenesis of asthma. Airway epithelial cells are in direct contact with environmental particles and serve as the first line of defense against inhaled allergens and pathogens. The potential contributions of airway epithelial cells to chitin-induced asthma remain poorly understood. We hypothesized that chitin directly stimulates airway epithelial cells to release cytokines that promote ...

  2. High glucose induces dysfunction of airway epithelial barrier through down-regulation of connexin 43.

    Science.gov (United States)

    Yu, Hongmei; Yang, Juan; Zhou, Xiangdong; Xiao, Qian; Lü, Yang; Xia, Li

    2016-03-01

    The airway epithelium is a barrier to the inhaled antigens and pathogens. Connexin 43 (Cx43) has been found to play critical role in maintaining the function of airway epithelial barrier and be involved in the pathogenesis of the diabetic retinal vasculature, diabetes nephropathy and diabetes skin. Hyperglycemia has been shown to be an independent risk factor for respiratory infections. We hypothesize that the down-regulation of Cx43 induced by HG alters the expression of tight junctions (zonula occludens-1 (ZO-1) and occludin) and contributes to dysfunction of airway epithelial barrier, and Cx43 plays a critical role in the process in human airway epithelial cells (16 HBE). We show that high glucose (HG) decreased the expression of ZO-1 and occludin, disassociated interaction between Cx43 and tight junctions, and then increased airway epithelial transepithelial electrical resistance (TER) and permeability by down-regulation of Cx43 in human airway epithelial cells. These observations demonstrate an important role for Cx43 in regulating HG-induced dysfunction of airway epithelial barrier. These findings may bring new insights into the molecular pathogenesis of pulmonary infection related to diabetes mellitus and lead to novel therapeutic intervention for the dysfunction of airway epithelial barrier in chronic inflammatory airway diseases. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. The Diacetyl-Exposed Human Airway Epithelial Secretome: New Insights into Flavoring-Induced Airways Disease.

    Science.gov (United States)

    Brass, David M; Gwinn, William M; Valente, Ashlee M; Kelly, Francine L; Brinkley, Christie D; Nagler, Andrew E; Moseley, M Arthur; Morgan, Daniel L; Palmer, Scott M; Foster, Matthew W

    2017-06-01

    Bronchiolitis obliterans (BO) is an increasingly important lung disease characterized by fibroproliferative airway lesions and decrements in lung function. Occupational exposure to the artificial food flavoring ingredient diacetyl, commonly used to impart a buttery flavor to microwave popcorn, has been associated with BO development. In the occupational setting, diacetyl vapor is first encountered by the airway epithelium. To better understand the effects of diacetyl vapor on the airway epithelium, we used an unbiased proteomic approach to characterize both the apical and basolateral secretomes of air-liquid interface cultures of primary human airway epithelial cells from four unique donors after exposure to an occupationally relevant concentration (∼1,100 ppm) of diacetyl vapor or phosphate-buffered saline as a control on alternating days. Basolateral and apical supernatants collected 48 h after the third exposure were analyzed using one-dimensional liquid chromatography tandem mass spectrometry. Paired t tests adjusted for multiple comparisons were used to assess differential expression between diacetyl and phosphate-buffered saline exposure. Of the significantly differentially expressed proteins identified, 61 were unique to the apical secretome, 81 were unique to the basolateral secretome, and 11 were present in both. Pathway enrichment analysis using publicly available databases revealed that proteins associated with matrix remodeling, including degradation, assembly, and new matrix organization, were overrepresented in the data sets. Similarly, protein modifiers of epidermal growth factor receptor signaling were significantly altered. The ordered changes in protein expression suggest that the airway epithelial response to diacetyl may contribute to BO pathogenesis.

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

    NARCIS (Netherlands)

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

    2015-01-01

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

  5. Bronchoconstriction Induces TGF-β Release and Airway Remodelling in Guinea Pig Lung Slices.

    Directory of Open Access Journals (Sweden)

    Tjitske A Oenema

    Full Text Available Airway remodelling, including smooth muscle remodelling, is a primary cause of airflow limitation in asthma. Recent evidence links bronchoconstriction to airway remodelling in asthma. The mechanisms involved are poorly understood. A possible player is the multifunctional cytokine TGF-β, which plays an important role in airway remodelling. Guinea pig lung slices were used as an in vitro model to investigate mechanisms involved in bronchoconstriction-induced airway remodelling. To address this aim, mechanical effects of bronchoconstricting stimuli on contractile protein expression and TGF-β release were investigated. Lung slices were viable for at least 48 h. Both methacholine and TGF-β1 augmented the expression of contractile proteins (sm-α-actin, sm-myosin, calponin after 48 h. Confocal fluorescence microscopy showed that increased sm-myosin expression was enhanced in the peripheral airways and the central airways. Mechanistic studies demonstrated that methacholine-induced bronchoconstriction mediated the release of biologically active TGF-β, which caused the increased contractile protein expression, as inhibition of actin polymerization (latrunculin A or TGF-β receptor kinase (SB431542 prevented the methacholine effects, whereas other bronchoconstricting agents (histamine and KCl mimicked the effects of methacholine. Collectively, bronchoconstriction promotes the release of TGF-β, which induces airway smooth muscle remodelling. This study shows that lung slices are a useful in vitro model to study mechanisms involved in airway remodelling.

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

    Science.gov (United States)

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

    1999-02-01

    The mechanism of cold-induced bronchoconstriction is poorly understood. This prompted the present study whose aim was to determine the step-wise direct effect of cooling on smooth muscle of isolated ovine airways and analyse the role of calcium in the mechanisms involved. Isolated tracheal strips and bronchial segments were suspended in organ baths containing Krebs' solution for isometric tension recording. Tissue responses during stepwise cooling from 37 to 5 degrees C were examined. Cooling induced a rapid and reproducible contraction proportional to cooling temperature in ovine tracheal and bronchial preparations which was epithelium-independent. On readjustment to 37 degrees C the tone returned rapidly to basal level. Maximum contraction was achieved at a temperature of 5 degrees C for trachea and 15 degrees C for bronchiole. Cooling-induced contractions (CIC) was resistant to tetrodotoxin (1; 10 micrometer), and not affected by the muscarinic antagonist atropine (1 micrometer) or the alpha-adrenergic antagonist phentolamine (1 micrometer), or the histamine H1-antagonist mepyramine (1 micrometer) or indomethacin (1 micrometer). Ca2+ antagonists (nifedipine and verapamil) and Mn2+ raised tracheal but not bronchiolar tone and augmented CIC. Incubation in Ca2+-free, EGTA-containing Krebs' solution for 5 min had no effect on CIC, although it significantly reduced KCl-induced contraction by up to 75%. Cooling inhibited Ca2+ influx measured using 45Ca2+ uptake. Caffeine (100 micrometer) significantly inhibited CIC. The results show that cooling-induced contractions do not appear to involve activation of nerve endings, all surface reception systems or Ca2+ influx. However, CIC is mainly dependent on release of intracellular Ca2+.

  7. A study on the relevance of airway inflammatory indices in induced sputum and airway hyperresponsiveness in asthmatics

    Institute of Scientific and Technical Information of China (English)

    厐亚敏

    2006-01-01

    Objective To analyze the correlations between NO3-/NO2-,eosinophil counts in induced sputum and airway hyperresponsiveness (AHR) and therefore to explore the clinical significance of these parameters in severity assessment and medication adjustment in patients with mild to moderate asthma. Methods From February 2003 to June 2004,35 outpatients with mild to moderate persistent asthma (mild:9, moderate:26) from Huaxi Hospital asthma clinic were treated with combined medi-

  8. Baicalein reduces airway injury in allergen and IL-13 induced airway inflammation.

    Directory of Open Access Journals (Sweden)

    Ulaganathan Mabalirajan

    Full Text Available BACKGROUND: Baicalein, a bioflavone present in the dry roots of Scutellaria baicalensis Georgi, is known to reduce eotaxin production in human fibroblasts. However, there are no reports of its anti-asthma activity or its effect on airway injury. METHODOLOGY/PRINCIPAL FINDINGS: In a standard experimental asthma model, male Balb/c mice that were sensitized with ovalbumin (OVA, treated with baicalein (10 mg/kg, ip or a vehicle control, either during (preventive use or after OVA challenge (therapeutic use. In an alternate model, baicalein was administered to male Balb/c mice which were given either IL-4 or IL-13 intranasally. Features of asthma were determined by estimating airway hyperresponsiveness (AHR, histopathological changes and biochemical assays of key inflammatory molecules. Airway injury was determined with apoptotic assays, transmission electron microscopy and assessing key mitochondrial functions. Baicalein treatment reduced AHR and inflammation in both experimental models. TGF-β₁, sub-epithelial fibrosis and goblet cell metaplasia, were also reduced. Furthermore, baicalein treatment significantly reduced 12/15-LOX activity, features of mitochondrial dysfunctions, and apoptosis of bronchial epithelia. CONCLUSION/SIGNIFICANCE: Our findings demonstrate that baicalein can attenuate important features of asthma, possibly through the reduction of airway injury and restoration of mitochondrial function.

  9. Hemodynamics and early recovery characteristics of desflurane versus sevoflurane in bariatric surgery

    Directory of Open Access Journals (Sweden)

    Amandeep Kaur

    2013-01-01

    Conclusions: Both desflurane and sevoflurane produce similar hemodynamic changes but the immediate and intermediate recovery was significantly faster after desflurane thus contributing to fast tracking and early discharge of patients.

  10. Comparison between sevoflurane and desflurane on emergence and recovery characteristics of children undergoing surgery for spinal dysraphism

    Directory of Open Access Journals (Sweden)

    Priyanka Gupta

    2015-01-01

    Full Text Available Background and Aims: Rapid recovery is desirable after neurosurgery as it enables early post-operative neurological evaluation and prompt management of complications. Studies have been rare comparing the recovery characteristics in paediatric neurosurgical patients. Hence, this study was carried out to compare the effect of sevoflurane and desflurane anaesthesia on emergence and extubation in children undergoing spinal surgery. Methods: Sixty children, aged 1-12 years, undergoing elective surgery for lumbo-sacral spinal dysraphism were enrolled. Anaesthesia was induced with sevoflurane using a face mask. The children were then randomised to receive either sevoflurane or desflurane with oxygen and nitrous oxide, fentanyl (1 μg/kg/h and rocuronium. The anaesthetic depth was guided by bispectral index (BIS ® monitoring with a target BIS ® between 45 and 55. Perioperative data with regard to demographic profile, haemodynamics, emergence and extubation times, modified Aldrete score (MAS, pain (objective pain score, agitation (Cole′s agitation score, time to first analgesic and complications, thereof, were recorded. Statistical analysis was done using STATA 11.2 (StataCorp., College Station, TX, USA and data are presented as median (range or mean ± standard deviation. Results: The demographic profile, haemodynamics, MAS, pain and agitation scores and time to first analgesic were comparable in between the two groups (P > 0.05. The emergence time was shorter in desflurane group (2.75 [0.85-12] min as compared to sevoflurane (8 [2.5-14] min (P < 0.0001. The extubation time was also shorter in desflurane group (3 [0.8-10] min as compared to the sevoflurane group (5.5 [1.2-14] min (P = 0.0003. Conclusion: Desflurane provided earlier tracheal extubation and emergence as compared to sevoflurane in children undergoing surgery for lumbo-sacral spinal dysraphism.

  11. Comparison between sevoflurane and desflurane on emergence and recovery characteristics of children undergoing surgery for spinal dysraphism

    Science.gov (United States)

    Gupta, Priyanka; Rath, Girija Prasad; Prabhakar, Hemanshu; Bithal, Parmod Kumar

    2015-01-01

    Background and Aims: Rapid recovery is desirable after neurosurgery as it enables early post-operative neurological evaluation and prompt management of complications. Studies have been rare comparing the recovery characteristics in paediatric neurosurgical patients. Hence, this study was carried out to compare the effect of sevoflurane and desflurane anaesthesia on emergence and extubation in children undergoing spinal surgery. Methods: Sixty children, aged 1–12 years, undergoing elective surgery for lumbo-sacral spinal dysraphism were enrolled. Anaesthesia was induced with sevoflurane using a face mask. The children were then randomised to receive either sevoflurane or desflurane with oxygen and nitrous oxide, fentanyl (1 μg/kg/h) and rocuronium. The anaesthetic depth was guided by bispectral index (BIS®) monitoring with a target BIS® between 45 and 55. Perioperative data with regard to demographic profile, haemodynamics, emergence and extubation times, modified Aldrete score (MAS), pain (objective pain score), agitation (Cole's agitation score), time to first analgesic and complications, thereof, were recorded. Statistical analysis was done using STATA 11.2 (StataCorp., College Station, TX, USA) and data are presented as median (range) or mean ± standard deviation. Results: The demographic profile, haemodynamics, MAS, pain and agitation scores and time to first analgesic were comparable in between the two groups (P > 0.05). The emergence time was shorter in desflurane group (2.75 [0.85–12] min) as compared to sevoflurane (8 [2.5–14] min) (P < 0.0001). The extubation time was also shorter in desflurane group (3 [0.8–10] min) as compared to the sevoflurane group (5.5 [1.2–14] min) (P = 0.0003). Conclusion: Desflurane provided earlier tracheal extubation and emergence as compared to sevoflurane in children undergoing surgery for lumbo-sacral spinal dysraphism. PMID:26379291

  12. 地氟醚七氟醚对糖尿病患者罗库溴铵肌松效应影响的比较%Effects of sevoflurane and desflurane on neuromuscular blockade induced by rocuronium in patients with diabetes mellitus

    Institute of Scientific and Technical Information of China (English)

    赵君

    2016-01-01

    Objective To compare the effects of sevoflurane and desflurane on neuromuscular blockade induced by rocuronium in patients with diabetes mellitus.Methods Sixty patients with diabetes mellitus, ASA Ⅱ and aged 45-64 y, scheduled for elective middle or lower abdominal surgery were included.All patients were randomly assigned to one of three groups (n=20): sevoflurane group (group SD), propofol group (group PD), and desflurane group (group DD).All patients were induced with midazolam, propofol and fentanyl.Anesthesia was maintained with propofol infusion, sevoflurane, or desflurane inhalation, respectively.Neuromuscular function was assessed by accelerography.Train-of-four stimulation (TOF) of ulnar nerve was used.The duration of action and recovery index (for T1 to return from 25% to 75% of the control twitch) were recorded.The T1/T0 and TOF (T4/T1) ratios were recorded at 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120 min after a single bolus of rocuronium.Results There was no significant difference in duration of action and the recovery index between group DD[(61± 17), (36±12) min] and group SD [(60±18), (35±10) min](P>0.05).The ratios of T1/T0 and TOF were not significantly different in group DD and group SD during 60 min to 120 min after a single bolus of rocuronium (P>0.05).Conclusions The effects of sevoflurane and desflurane on rocuronium induced neuromuscular blockade is similar in diabetic patients.%目的 比较地氟醚和七氟醚对糖尿病患者罗库溴铵肌松效应的影响.方法 择期2型糖尿病腹部手术患者60例,年龄45~64岁,ASA分级Ⅱ级,采用随机数字表法分为3组,每组20例:地氟醚组(DD组)、七氟醚组(SD组)和异丙酚组(PD组).静脉注射咪达唑仑、异丙酚和芬太尼行麻醉诱导后启动肌松监测,3组分别用异丙酚、地氟醚和七氟醚维持麻醉.记录肌松维持时间和恢复指数.于静脉注射罗库溴铵后10、20、30、40、50、60、70、80、90、100、110

  13. Platelet-derived growth factor mediates interleukin-13-induced collagen I production in mouse airway fibroblasts.

    Science.gov (United States)

    Lu, Jiamei; Zhu, Yanting; Feng, Wei; Pan, Yilin; Li, Shaojun; Han, Dong; Liu, Lu; Xie, Xinming; Wang, Guizuo; Li, Manxiang

    2014-09-01

    Interleukin-13 (IL-13) is associated with the production of collagen in airway remodelling of asthma. Yet, the molecular mechanisms underlying IL-13 induction of collagen remain unclear; the aim of this study is to address this issue. IL-13 dose- and time-dependently-induced collagen I production in primary cultured airway fibroblasts; this was accompanied with the STAT6 phosphorylation, and pre-treatment of cells with JAK inhibitor suppressed IL-13- induced collagen I production. Further study indicated that IL-13 stimulated JAK/STAT6-dependent PDGF production and subsequent ERK1/2 MAPK activation in airway fibroblasts, and the presence of either PDGF receptor blocker or MEK inhibitor partially suppressed IL-13-induced collagen I production. Taken together, our study suggests that activation of JAK/STAT6 signal pathway and subsequent PDGF generation and resultant ERK1/2 MAPK activation mediated IL-13-induced collagen I production in airway fibroblasts.

  14. Platelet-derived growth factor mediates interleukin-13-induced collagen I production in mouse airway fibroblasts

    Indian Academy of Sciences (India)

    Jiamei Lu; Yanting Zhu; Wei Feng; Yilin Pan; Shaojun Li; Dong Han; Lu Liu; Xinming Xie; Guizuo Wang; Manxiang Li

    2014-09-01

    Interleukin-13 (IL-13) is associated with the production of collagen in airway remodelling of asthma. Yet, the molecular mechanisms underlying IL-13 induction of collagen remain unclear; the aim of this study is to address this issue. IL-13 dose- and time-dependently-induced collagen I production in primary cultured airway fibroblasts; this was accompanied with the STAT6 phosphorylation, and pre-treatment of cells with JAK inhibitor suppressed IL-13-induced collagen I production. Further study indicated that IL-13 stimulated JAK/STAT6-dependent PDGF production and subsequent ERK1/2 MAPK activation in airway fibroblasts, and the presence of either PDGF receptor blocker or MEK inhibitor partially suppressed IL-13-induced collagen I production. Taken together, our study suggests that activation of JAK/STAT6 signal pathway and subsequent PDGF generation and resultant ERK1/2 MAPK activation mediated IL-13-induced collagen I production in airway fibroblasts.

  15. Ventilation and Perfusion Lung Scintigraphy of Allergen-Induced Airway Responses in Atopic Asthmatic Subjects

    Directory of Open Access Journals (Sweden)

    Krishnan Parameswaran

    2007-01-01

    Full Text Available BACKGROUND: Both ventilation (V and perfusion (Q of the lungs are altered in asthma, but their relationships with allergen-induced airway responses and gas exchange are not well described.

  16. PPAR-γ inhibits IL-13-induced collagen production in mouse airway fibroblasts.

    Science.gov (United States)

    Lu, Jiamei; Liu, Lu; Zhu, Yanting; Zhang, Yonghong; Wu, Yuanyuan; Wang, Guizuo; Zhang, Dexin; Xu, Jing; Xie, Xinming; Ke, Rui; Han, Dong; Li, Shaojun; Feng, Wei; Xie, Mei; Liu, Yun; Fang, Ping; Shi, Hongyang; He, Ping; Liu, Yuan; Sun, Xiuzhen; Li, Manxiang

    2014-08-15

    Interleukin-13 (IL-13) plays an important role in extracellular matrix production of airway remodeling in asthma. Activation of PPAR-γ has been shown to inhibit the occurrence of airway fibrosis in asthma, yet it remains unknown whether the effect of PPAR-γ on suppression of airway fibrosis is associated with the inhibition of IL-13 signaling. In the present study, primary cultured airway fibroblasts were stimulated with IL-13, and JAK inhibitor, PDGF receptor blocker and MEK inhibitor were applied to investigate the involvement of these pathways in IL-13-induced collagen production. Our results demonstrate that IL-13 dose- and time-dependently induced collagen production in primary cultured mouse airway fibroblasts; this effect was blocked by inhibition of JAK/STAT6 signal pathway. IL-13 also stimulated JAK/STAT6-dependent PDGF production, elevation of PDGF in turn activated ERK1/2 MAPK and caused collagen production. Activation of PPAR-γ by rosiglitazone reduced IL-13-induced collagen expression by suppression of STAT6-driven PDGF production. Our results indicate that activation of JAK/STAT6 signal and subsequent PDGF generation and ERK1/2 MAPK activation mediate IL-13-induced collagen production in airway fibroblasts. This study suggests that activation of PPAR-γ might be a novel strategy for the treatment of asthma partially by inhibition of airway fibrosis.

  17. Prevention of house dust mite induced allergic airways disease in mice through immune tolerance.

    Science.gov (United States)

    Agua-Doce, Ana; Graca, Luis

    2011-01-01

    Allergic airways disease is a consequence of a Th2 response to an allergen leading to a series of manifestations such as production of allergen-specific IgE, inflammatory infiltrates in the airways, and airway hyper-reactivity (AHR). Several strategies have been reported for tolerance induction to allergens leading to protection from allergic airways disease. We now show that CD4 blockade at the time of house dust mite sensitization induces antigen-specific tolerance in mice. Tolerance induction is robust enough to be effective in pre-sensitized animals, even in those where AHR was pre-established. Tolerant mice are protected from airways eosinophilia, Th2 lung infiltration, and AHR. Furthermore, anti-CD4 treated mice remain immune competent to mount immune responses, including Th2, to unrelated antigens. Our findings, therefore, describe a strategy for tolerance induction potentially applicable to other immunogenic proteins besides allergens.

  18. Airways Hyperresponsiveness Following a Single Inhalation Exposure to Doxorubicin-Induced Heart Failure Prevents Airways Transition Metal-Rich Particulate Matter in Hypertensive Rats

    Science.gov (United States)

    Exposure to particulate matter (PM) air pollution results in airways hyperresponsiveness (AHR), however it also results in adverse cardiovascular effects, particularly in individuals with underlying cardiovascular disease. The impact of pre-existing cardiac deficit on PM-induced ...

  19. IL-18 induces airway hyperresponsiveness and pulmonary inflammation via CD4+ T cell and IL-13.

    Directory of Open Access Journals (Sweden)

    Masanori Sawada

    Full Text Available IL-18 plays a key role in the pathogenesis of pulmonary inflammatory diseases including pulmonary infection, pulmonary fibrosis, lung injury and chronic obstructive pulmonary disease (COPD. However, it is unknown whether IL-18 plays any role in the pathogenesis of asthma. We hypothesized that overexpression of mature IL-18 protein in the lungs may exacerbate disease activities of asthma. We established lung-specific IL-18 transgenic mice on a Balb/c genetic background. Female mice sensitized- and challenged- with antigen (ovalbumin were used as a mouse asthma model. Pulmonary inflammation and emphysema were not observed in the lungs of naïve transgenic mice. However, airway hyperresponsiveness and airway inflammatory cells accompanied with CD4(+ T cells, CD8(+ T cells, eosinophils, neutrophils, and macrophages were significantly increased in ovalbumin-sensitized and challenged transgenic mice, as compared to wild type Balb/c mice. We also demonstrate that IL-18 induces IFN-γ, IL-13, and eotaxin in the lungs of ovalbumin-sensitized and challenged transgenic mice along with an increase in IL-13 producing CD4(+ T cells. Treatment with anti-CD4 monoclonal antibody or deletion of the IL-13 gene improves ovalbumin-induced airway hyperresponsiveness and reduces airway inflammatory cells in transgenic mice. Overexpressing the IL-18 protein in the lungs induces type 1 and type 2 cytokines and airway inflammation, and results in increasing airway hyperresponsiveness via CD4(+ T cells and IL-13 in asthma.

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

    Science.gov (United States)

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

    2016-01-01

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

  1. Toll-like receptor 2 regulates organic dust-induced airway inflammation.

    Science.gov (United States)

    Poole, Jill A; Wyatt, Todd A; Kielian, Tammy; Oldenburg, Peter; Gleason, Angela M; Bauer, Ashley; Golden, Gregory; West, William W; Sisson, Joseph H; Romberger, Debra J

    2011-10-01

    Organic dust exposure in agricultural environments results in significant airway inflammatory diseases. Gram-positive cell wall components are present in high concentrations in animal farming dusts, but their role in mediating dust-induced airway inflammation is not clear. This study investigated the role of Toll-like receptor (TLR) 2, a pattern recognition receptor for gram-positive cell wall products, in regulating swine facility organic dust extract (DE)-induced airway inflammation in mice. Isolated lung macrophages from TLR2 knockout mice demonstrated reduced TNF-α, IL-6, keratinocyte chemoattractant/CXCL1, but not macrophage inflammatory protein-2/CXCL2 expression, after DE stimulation ex vivo. Next, using an established mouse model of intranasal inhalation challenge, we analyzed bronchoalveolar lavage fluid and lung tissue in TLR2-deficient and wild-type (WT) mice after single and repetitive DE challenge. Neutrophil influx and select cytokines/chemokines were significantly lower in TLR2-deficient mice at 5 and 24 hours after single DE challenge. After daily exposure to DE for 2 weeks, there were significant reductions in total cellularity, neutrophil influx, and TNF-α, IL-6, CXCL1, but not CXCL2 expression, in TLR2-deficient mice as compared with WT animals. Lung pathology revealed that bronchiolar inflammation, but not alveolar inflammation, was reduced in TLR2-deficient mice after repetitive exposure. Airway hyperresponsiveness to methacholine after dust exposure was similar in both groups. Finally, airway inflammatory responses in WT mice after challenge with a TLR2 agonist, peptidoglycan, resembled DE-induced responses. Collectively, these results demonstrate that the TLR2 pathway is important in regulating swine facility organic dust-induced airway inflammation, which suggests the importance of TLR2 agonists in mediating large animal farming-induced airway inflammatory responses.

  2. SUSCEPTIBILITY TO POLLUTANT-INDUCED AIRWAY INFLAMMATION IS NEUROGENICALLY MEDIATED.

    Science.gov (United States)

    Neurogenic inflammation in the airways involves the activation of sensory irritant receptors (capsaicin, VR1) by noxious stimuli and the subsequent release of neuropeptides (e.g., SP, CGRP, NKA) from these fibers. Once released, these peptides initiate and sustain symptoms of ...

  3. The effects of desflurane and remifentanyl anaesthesia compared to lumbar epidural analgesia combined with desflurane on recovery

    Directory of Open Access Journals (Sweden)

    Celaleddin Soyalp

    2014-12-01

    Full Text Available Objective: Our primary objective in this study is to compare the effects of the applications of desflurane and remifentanyl anaesthesia, along with lumbar epidural analgesia combined with desflurane on postoperative recovery in the cases who undergoing lower abdominal surgery. Methods: This study performed 240 patients who undergoing elective lower abdominal surgery. Patients were divided into two random groups as Group DR (desflurane + remifentanyl n=120 and Group DL (desflurane +Lumbar Epidural Analgesia n=120.The general anaesthesia in Group DR was performed through the use of desflurane and remifentanyl. Group DL was administered a general anaesthesia through a pre-operative epidural catheter insertion and an application of desflurane. Extubation, eye opening, head lift for 5 seconds, and the surgical durations of the patients as well as the postoperative side-effects were recorded. Modified Aldrete Scoring System was used to assess the recovery of the patients from anaesthesia. Results: According to the inter group comparison results between Group DR and Group DL, the duration of extubation, eye opening, head lift for 5 seconds and the average amount of elapsed time until the modified Aldrete Scoring reached 10 were found statistically and significantly shorter in Group DL than Group DR( respectively p=0.002, p<0.001, p<0.001, p<0.001.The duration of the first analgesic need was statistically and significantly longer in Group DL compared to Group DR (p<0.001. The postoperative patient satisfaction in Group DL was statistically and significantly higher than that in Group DR (p=0.010. Conclusion: The Epidural analgesia included in the general anaesthesia in lower abdominal surgery is considered by us to be the beneficial and efficient method of analgesia which leads to an earlier recovery of the patients without affecting the intraoperative hemodynamic stability and which boosts the patient satisfaction by providing a more efficient analgesia

  4. Attenuation of cigarette smoke-induced airway mucus production by hydrogen-rich saline in rats.

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    Yunye Ning

    Full Text Available BACKGROUND: Over-production of mucus is an important pathophysiological feature in chronic airway disease such as chronic obstructive pulmonary disease (COPD and asthma. Cigarette smoking (CS is the leading cause of COPD. Oxidative stress plays a key role in CS-induced airway abnormal mucus production. Hydrogen protected cells and tissues against oxidative damage by scavenging hydroxyl radicals. In the present study we investigated the effect of hydrogen on CS-induced mucus production in rats. METHODS: Male Sprague-Dawley rats were divided into four groups: sham control, CS group, hydrogen-rich saline pretreatment group and hydrogen-rich saline control group. Lung morphology and tissue biochemical changes were determined by immunohistochemistry, Alcian Blue/periodic acid-Schiff staining, TUNEL, western blot and realtime RT-PCR. RESULTS: Hydrogen-rich saline pretreatment attenuated CS-induced mucus accumulation in the bronchiolar lumen, goblet cell hyperplasia, muc5ac over-expression and abnormal cell apoptosis in the airway epithelium as well as malondialdehyde increase in the BALF. The phosphorylation of EGFR at Tyr1068 and Nrf2 up-regulation expression in the rat lungs challenged by CS exposure were also abrogated by hydrogen-rich saline. CONCLUSION: Hydrogen-rich saline pretreatment ameliorated CS-induced airway mucus production and airway epithelium damage in rats. The protective role of hydrogen on CS-exposed rat lungs was achieved at least partly by its free radical scavenging ability. This is the first report to demonstrate that intraperitoneal administration of hydrogen-rich saline protected rat airways against CS damage and it could be promising in treating abnormal airway mucus production in COPD.

  5. Muscarinic receptors involved in airway vascular leakage induced by experimental gastro-oesophageal reflux.

    Science.gov (United States)

    Cui, Yong-Yao; Zhu, Liang; Wang, Hao; Advenier, Charles; Chen, Hong-Zhuan; Devillier, Philippe

    2008-04-23

    Gastro-oesophageal acid reflux may cause airway responses such as cough, bronchoconstriction and inflammation in asthmatic patients. Studies in humans or in animals have suggested that these responses involve cholinergic nerves. The purpose of this study was to investigate the role of the efferent vagal component on airway microvascular leakage induced by instillation of hydrochloric acid (HCl) into the oesophagus of guinea-pigs and the subtype of muscarinic receptors involved. Airway microvascular leakage induced by intra-oesophageal HCl instillation was abolished by bilateral vagotomy or by the nicotinic receptor antagonist, hexamethonium. HCl-induced leakage was inhibited by pretreatment with atropine, a non-specific muscarinic receptor antagonist, and also by pretreatment with either pirenzepine, a muscarinic M(1) receptor antagonist, or 4-DAMP, a muscarinic M(3) receptor antagonist. Pirenzepine was more potent than atropine and 4-DAMP. These antagonists were also studied on airway microvascular leakage or bronchoconstriction induced by intravenous administration of acetylcholine (ACh). Atropine, pirenzepine and 4-DAMP inhibited ACh-induced airway microvascular leakage with similar potencies. In sharp contrast, 4-DAMP and atropine were more potent inhibitors of ACh-induced bronchoconstriction than pirenzepine. Methoctramine, a muscarinic M(2) receptor antagonist, was ineffective in all experimental conditions. These results suggest that airway microvascular leakage caused by HCl intra-oesophageal instillation involves ACh release from vagus nerve terminals and that M(1) and M(3) receptors play a major role in cholinergic-mediated microvascular leakage, whereas M(3) receptors are mainly involved in ACh-induced bronchoconstriction.

  6. Comportamento da pressão intra-ocular segundo os efeitos cardiorrespiratórios e hemodinâmicos induzidos pela anestesia com desflurano, em cães submetidos à hipovolemia experimental Behavior of intraocular pressure according to cardiorespiratory and hemodynamic effects induced by desflurane in dogs subjected to experimental hypovolemia

    Directory of Open Access Journals (Sweden)

    Ivia Carmem Talieri

    2005-08-01

    Full Text Available OBJETIVOS: Observar o comportamento da pressão intra-ocular, segundo os efeitos cardiorrespiratórios e hemodinâmicos induzidos pela anestesia geral com desflurano, em cães submetidos à hipovolemia experimental. MÉTODOS: Foram utilizados 18 cães, machos e fêmeas, com peso entre 10 e 15 kg. A hipovolemia foi realizada retirando-se 40 ml de sangue/kg de peso. A seguir, a anestesia foi induzida com desflurano através de máscara facial, até que a intubação orotraqueal fosse permitida. A pressão intra-ocular foi medida por tonometria de aplanação. Valores para freqüência cardíaca, débito cardíaco, pressão arterial média, pressão venosa central e pressão parcial de CO2 ao final da expiração e freqüência respiratória foram mensurados. Os parâmetros da avaliação foram registrados após a instrumentalização e antes de qualquer outro procedimento (T0, quinze minutos depois da indução da hipovolemia experimental (T45 e após 30 minutos da indução anestésica (T75. RESULTADOS: A pressão intra-ocular apresentou relação direta somente com a pressão parcial de CO2 no final da expiração. CONCLUSÕES: Não foi possível estabelecer correlação entre alterações da pressão arterial média e da pressão venosa central com a pressão intra-ocular e houve relação direta entre os valores da pressão intra-ocular e os de ETCO2.PURPOSE: To observe the behavior of intraocular pressure according to the cardiopulmonary and hemodynamic effects induced by desflurane in dogs subjected to experimental hypovolemia. METHODS: Eighteen healthy male and female mongrel dogs, weighing between 10 and 15 kg were used. Hypovolemia was induced by withdrawal of 40 ml blood/kg body weight. Then anesthesia was induced with desflurane by mask until tracheal intubation was permitted. Intraocular pressure was measured with applanation tonometry. Heart rate, cardiac output, mean arterial pressure, central venous pressure, end-tidal concentration

  7. Salvinorin A Inhibits Airway Hyperreactivity Induced by Ovalbumin Sensitization

    OpenAIRE

    Rossi, Antonietta; Caiazzo, Elisabetta; Bilancia, Rossella; Riemma, Maria A.; Pagano, Ester; Cicala, Carla; Ialenti, Armando; Jordan K. Zjawiony; Izzo, Angelo A; Capasso, Raffaele; Roviezzo, Fiorentina

    2017-01-01

    Salvinorin A, a neoclerodane diterpene isolated from Salvia divinorum, exerts a number of pharmacological actions which are not solely limited to the central nervous system. Recently it has been demonstrated that Salvinorin A inhibits acute inflammatory response affecting leukotriene (LT) production. Since LTs are potent lipid mediators implicated in allergic diseases, we evaluated the effect of Salvinorin A on allergic inflammation and on airways following sensitization in the mouse. Mice we...

  8. Iptakalim inhibits PDGF-BB-induced human airway smooth muscle cells proliferation and migration.

    Science.gov (United States)

    Liu, Wenrui; Kong, Hui; Zeng, Xiaoning; Wang, Jingjing; Wang, Zailiang; Yan, Xiaopei; Wang, Yanli; Xie, Weiping; Wang, Hong

    2015-08-15

    Chronic airway diseases are characterized by airway remodeling which is attributed partly to the proliferation and migration of airway smooth muscle cells (ASMCs). ATP-sensitive potassium (KATP) channels have been identified in ASMCs. Mount evidence has suggested that KATP channel openers can reduce airway hyperresponsiveness and alleviate airway remodeling. Opening K(+) channels triggers K(+) efflux, which leading to membrane hyperpolarization, preventing Ca(2+)entry through closing voltage-operated Ca(2+) channels. Intracellular Ca(2+) is the most important regulator of muscle contraction, cell proliferation and migration. K(+) efflux decreases Ca(2+) influx, which consequently influences ASMCs proliferation and migration. As a KATP channel opener, iptakalim (Ipt) has been reported to restrain the proliferation of pulmonary arterial smooth muscle cells (PASMCs) involved in vascular remodeling, while little is known about its impact on ASMCs. The present study was designed to investigate the effects of Ipt on human ASMCs and the mechanisms underlying. Results obtained from cell counting kit-8 (CCK-8), flow cytometry and 5-ethynyl-2'-deoxyuridine (EdU) incorporation showed that Ipt significantly inhibited platelet-derived growth factor (PDGF)-BB-induced ASMCs proliferation. ASMCs migration induced by PDGF-BB was also suppressed by Ipt in transwell migration and scratch assay. Besides, the phosphorylation of Ca(2+)/calmodulin-dependent kinase II (CaMKII), extracellular regulated protein kinases 1/2 (ERK1/2), protein kinase B (Akt), and cyclic adenosine monophosphate (cAMP) response element binding protein (CREB) were as well alleviated by Ipt administration. Furthermore, we found that the inhibition of Ipt on the PDGF-BB-induced proliferation and migration in human ASMCs was blocked by glibenclamide (Gli), a selective KATP channel antagonist. These findings provide a strong evidence to support that Ipt antagonize the proliferating and migrating effects of PDGF-BB on

  9. IL-17A modulates oxidant stress-induced airway hyperresponsiveness but not emphysema.

    Science.gov (United States)

    Pinart, Mariona; Zhang, Min; Li, Feng; Hussain, Farhana; Zhu, Jie; Wiegman, Coen; Ryffel, Bernard; Chung, Kian Fan

    2013-01-01

    IL-17A induces the release of pro-inflammatory cytokines and of reactive oxygen species which could lead to neutrophilic inflammation. We determined the role of IL-17 receptor (IL-17R) signalling in oxidant-induced lung emphysema and airway hyperresponsiveness. IL-17R(-/-) and wild-type C57/BL6 mice were exposed to ozone (3 ppm; 3 hours) for 12 times over 6 weeks. Bronchial responsiveness to acetylcholine was measured, and lungs were retrieved. Mean linear intercept (Lm) and isometric contractile responses of intrapulmonary airways to acetylcholine were determined. In wild-type mice but not in IL-17R(-/-), chronic ozone exposure caused airway hyperresponsiveness. The increase in Lm after chronic ozone exposure of wild-type mice was also observed in IL-17R(-/-) mice. The increased maximal contractile response to acetylcholine seen in airways of wild-type mice exposed to ozone was abolished in IL-17R(-/-) mice. p38-mitogen-activated protein kinase (MAPK) and dexamethasone-dependent increase in contractile response was reduced in airways from IL-17R(-/-) ozone-exposed mice. Lung inflammation scores were not altered in IL-17R(-/-) mice exposed to ozone compared to wild-type mice. The increased release of IL-17 and IL-1β, and the activation of p38 MAPK in the lungs of ozone-exposed mice was reduced in IL-17R(-/-) mice. IL-17R signalling underlies the increase in airway hyperresponsiveness seen after ozone exposure, mediated by the increased contractility of airway smooth muscle. The emphysema and lung inflammation induced by ozone is not dependent on IL-17.

  10. IL-17A modulates oxidant stress-induced airway hyperresponsiveness but not emphysema.

    Directory of Open Access Journals (Sweden)

    Mariona Pinart

    Full Text Available IL-17A induces the release of pro-inflammatory cytokines and of reactive oxygen species which could lead to neutrophilic inflammation. We determined the role of IL-17 receptor (IL-17R signalling in oxidant-induced lung emphysema and airway hyperresponsiveness. IL-17R(-/- and wild-type C57/BL6 mice were exposed to ozone (3 ppm; 3 hours for 12 times over 6 weeks. Bronchial responsiveness to acetylcholine was measured, and lungs were retrieved. Mean linear intercept (Lm and isometric contractile responses of intrapulmonary airways to acetylcholine were determined. In wild-type mice but not in IL-17R(-/-, chronic ozone exposure caused airway hyperresponsiveness. The increase in Lm after chronic ozone exposure of wild-type mice was also observed in IL-17R(-/- mice. The increased maximal contractile response to acetylcholine seen in airways of wild-type mice exposed to ozone was abolished in IL-17R(-/- mice. p38-mitogen-activated protein kinase (MAPK and dexamethasone-dependent increase in contractile response was reduced in airways from IL-17R(-/- ozone-exposed mice. Lung inflammation scores were not altered in IL-17R(-/- mice exposed to ozone compared to wild-type mice. The increased release of IL-17 and IL-1β, and the activation of p38 MAPK in the lungs of ozone-exposed mice was reduced in IL-17R(-/- mice. IL-17R signalling underlies the increase in airway hyperresponsiveness seen after ozone exposure, mediated by the increased contractility of airway smooth muscle. The emphysema and lung inflammation induced by ozone is not dependent on IL-17.

  11. Waterpipe smoking induces epigenetic changes in the small airway epithelium.

    Science.gov (United States)

    Walters, Matthew S; Salit, Jacqueline; Ju, Jin Hyun; Staudt, Michelle R; Kaner, Robert J; Rogalski, Allison M; Sodeinde, Teniola B; Rahim, Riyaad; Strulovici-Barel, Yael; Mezey, Jason G; Almulla, Ahmad M; Sattar, Hisham; Mahmoud, Mai; Crystal, Ronald G

    2017-01-01

    Waterpipe (also called hookah, shisha, or narghile) smoking is a common form of tobacco use in the Middle East. Its use is becoming more prevalent in Western societies, especially among young adults as an alternative form of tobacco use to traditional cigarettes. While the risk to cigarette smoking is well documented, the risk to waterpipe smoking is not well defined with limited information on its health impact at the epidemiologic, clinical and biologic levels with respect to lung disease. Based on the knowledge that airway epithelial cell DNA methylation is modified in response to cigarette smoke and in cigarette smoking-related lung diseases, we assessed the impact of light-use waterpipe smoking on DNA methylation of the small airway epithelium (SAE) and whether changes in methylation were linked to the transcriptional output of the cells. Small airway epithelium was obtained from 7 nonsmokers and 7 light-use (2.6 ± 1.7 sessions/wk) waterpipe-only smokers. Genome-wide comparison of SAE DNA methylation of waterpipe smokers to nonsmokers identified 727 probesets differentially methylated (fold-change >1.5, pwaterpipe smoking is associated with epigenetic changes and related transcriptional modifications in the SAE, the cell population demonstrating the earliest pathologic abnormalities associated with chronic cigarette smoking.

  12. Ambient particulate matter induces an exacerbation of airway inflammation in experimental asthma: role of interleukin-33.

    Science.gov (United States)

    Shadie, A M; Herbert, C; Kumar, R K

    2014-08-01

    High levels of ambient environmental particulate matter (PM10 i.e. interleukin (IL)-33 in airway tissues and an increased concentration of IL-33 in bronchoalveolar lavage fluid. Administration of a monoclonal neutralizing anti-mouse IL-33 antibody prior to delivery of particulates significantly suppressed the inflammatory response induced by Sydney PM10, as well as the levels of associated proinflammatory cytokines in lavage fluid. We conclude that IL-33 plays a key role in driving airway inflammation in this novel experimental model of an acute exacerbation of chronic allergic asthma induced by exposure to PM10.

  13. Comparative pharmacodynamic modeling of desflurane, sevoflurane and isoflurane.

    NARCIS (Netherlands)

    Kreuer, S.; Bruhn, J.; Wilhelm, W.; Grundmann, U.; Rensing, H.; Ziegeler, S.

    2009-01-01

    BACKGROUND: We compared dose-response curves of the hypnotic effects of desflurane, sevoflurane and isoflurane. In addition, we analyzed the k(e0) values of the different anesthetics. The EEG parameters Bispectral index (BIS, Aspect Medical Systems, Natick, MA, version XP) and Narcotrend index (Moni

  14. Pulse pressure variation and stroke volume variation under different inhaled concentrations of isoflurane, sevoflurane and desflurane in pigs undergoing hemorrhage

    Directory of Open Access Journals (Sweden)

    Alexandre Hideaki Oshiro

    2015-12-01

    Full Text Available OBJECTIVES: Inhalant anesthesia induces dose-dependent cardiovascular depression, but whether fluid responsiveness is differentially influenced by the inhalant agent and plasma volemia remains unknown. The aim of this study was to compare the effects of isoflurane, sevoflurane and desflurane on pulse pressure variation and stroke volume variation in pigs undergoing hemorrhage. METHODS: Twenty-five pigs were randomly anesthetized with isoflurane, sevoflurane or desflurane. Hemodynamic and echocardiographic data were registered sequentially at minimum alveolar concentrations of 1.00 (M1, 1.25 (M2, and 1.00 (M3. Then, following withdrawal of 30% of the estimated blood volume, these data were registered at a minimum alveolar concentrations of 1.00 (M4 and 1.25 (M5. RESULTS: The minimum alveolar concentration increase from 1.00 to 1.25 (M2 decreased the cardiac index and increased the central venous pressure, but only modest changes in mean arterial pressure, pulse pressure variation and stroke volume variation were observed in all groups from M1 to M2. A significant decrease in mean arterial pressure was only observed with desflurane. Following blood loss (M4, pulse pressure variation, stroke volume variation and central venous pressure increased (p <0.001 and mean arterial pressure decreased in all groups. Under hypovolemia, the cardiac index decreased with the increase of anesthesia depth in a similar manner in all groups. CONCLUSION: The effects of desflurane, sevoflurane and isoflurane on pulse pressure variation and stroke volume variation were not different during normovolemia or hypovolemia.

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

    Directory of Open Access Journals (Sweden)

    Maryam Adelipour

    2011-09-01

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

  16. Induced Sputum for the Investigation of Airway Inflammation: Evidence for Its Clinical Application

    Directory of Open Access Journals (Sweden)

    Frederick E Hargreave

    1999-01-01

    Full Text Available Airway inflammation is considered to be the primary cause of airway diseases. Its prevention and reversal are the primary aims of treatment. Measurement of the inflammation is now possible relatively noninvasively and reliably by using induced sputum cell counts. The differential count indicates the presence and type of the inflammation (eosinophilic or neutrophilic and the total cell count the intensity. Sputum eosinophilia responds to treatment with corticosteroid, while there is increasing evidence that an isolated neutrophilia does not. Clinical judgement of airway inflammation is made difficult because of the different types of inflammation and their inconsistent correlation with the clinical features. Hence, reliable measurement of induced sputum cell counts may be useful to guide treatment in clinical practice. Consideration should now be given as to how to make it more available.

  17. Mucosal exposure to cockroach extract induces allergic sensitization and allergic airway inflammation

    Directory of Open Access Journals (Sweden)

    Arizmendi Narcy G

    2011-12-01

    Full Text Available Abstract Background Allergic sensitization to aeroallergens develops in response to mucosal exposure to these allergens. Allergic sensitization may lead to the development of asthma, which is characterized by chronic airway inflammation. The objective of this study is to describe in detail a model of mucosal exposure to cockroach allergens in the absence of an exogenous adjuvant. Methods Cockroach extract (CE was administered to mice intranasally (i.n. daily for 5 days, and 5 days later mice were challenged with CE for 4 consecutive days. A second group received CE i.n. for 3 weeks. Airway hyperresponsiveness (AHR was assessed 24 h after the last allergen exposure. Allergic airway inflammation was assessed by BAL and lung histology 48 h after the last allergen exposure. Antigen-specific antibodies were assessed in serum. Lungs were excised from mice from measurement of cytokines and chemokines in whole lung lysate. Results Mucosal exposure of Balb/c mice to cockroach extract induced airway eosinophilic inflammation, AHR and cockroach-specific IgG1; however, AHR to methacholine was absent in the long term group. Lung histology showed patchy, multicentric damage with inflammatory infiltrates at the airways in both groups. Lungs from mice from the short term group showed increased IL-4, CCL11, CXCL1 and CCL2 protein levels. IL4 and CXCL1 were also increased in the BAL of cockroach-sensitized mice in the short-term protocol. Conclusions Mucosal exposure to cockroach extract in the absence of adjuvant induces allergic airway sensitization characterized by AHR, the presence of Th2 cytokines in the lung and eosinophils in the airways.

  18. 20-HETE mediates ozone-induced, neutrophil-independent airway hyper-responsiveness in mice.

    Directory of Open Access Journals (Sweden)

    Philip R Cooper

    Full Text Available BACKGROUND: Ozone, a pollutant known to induce airway hyper-responsiveness (AHR, increases morbidity and mortality in patients with obstructive airway diseases and asthma. We postulate oxidized lipids mediate in vivo ozone-induced AHR in murine airways. METHODOLOGY/PRINCIPAL FINDINGS: Male BALB/c mice were exposed to ozone (3 or 6 ppm or filtered air (controls for 2 h. Precision cut lung slices (PCLS; 250 microm thickness containing an intrapulmonary airway ( approximately 0.01 mm(2 lumen area were prepared immediately after exposure or 16 h later. After 24 h, airways were contracted to carbachol (CCh. Log EC(50 and E(max values were then calculated by measuring the airway lumen area with respect to baseline. In parallel studies, dexamethasone (2.5 mg/kg, or 1-aminobenzotriazol (ABT (50 mg/kg were given intraperitoneal injection to naïve mice 18 h prior to ozone exposure. Indomethacin (10 mg/kg was administered 2 h prior. Cell counts, cytokine levels and liquid chromatography-mass spectrometry (LC-MS for lipid analysis were assessed in bronchoalveolar lavage (BAL fluid from ozone exposed and control mice. Ozone acutely induced AHR to CCh. Dexamethasone or indomethacin had little effect on the ozone-induced AHR; while, ABT, a cytochrome P450 inhibitor, markedly attenuated airway sensitivity. BAL fluid from ozone exposed animals, which did not contain an increase in neutrophils or interleukin (IL-6 levels, increased airway sensitivity following in vitro incubation with a naïve PCLS. In parallel, significant increases in oxidized lipids were also identified using LC-MS with increases of 20-HETE that were decreased following ABT treatment. CONCLUSIONS/SIGNIFICANCE: These data show that ozone acutely induces AHR to CCh independent of inflammation and is insensitive to steroid treatment or cyclooxygenase (COX inhibition. BAL fluid from ozone exposed mice mimicked the effects of in vivo ozone exposure that were associated with marked increases in

  19. Alteration of airway responsiveness mediated by receptors in ovalbumin-induced asthmatic E3 rats

    Institute of Scientific and Technical Information of China (English)

    Jing-wen LONG; Xu-dong YANG; Lei CAO; She-min LU; Yong-xiao CAO

    2009-01-01

    Aim:Airway hyperresponsiveness is a constant feature of asthma.The aim of the present study was to investigate airway hyperreactivity mediated by contractile and dilative receptors in an ovalbumin (OVA)-induced model of rat asthma.Methods:Asthmatic E3 rats were prepared by intraperitoneal injection with OVA/aluminum hydroxide and then challenged with intranasal instillation of OVA-PBS two weeks later.The myograph method was used to measure the responses of constriction and dilatation in the trachea,main bronchi and lobar bronchi.Results:In asthmatic E3 rata,β2 adrenoceptor-mediated relaxation of airway smooth muscle pre-contracted with 5-HT was inhibited,and there were no obvious difference in relaxation compared with normal E3 rats.Contraction of lobar bronchi mediated by 5-HT and sarafotoxin 6c was more potent than in the trachea or main bronchi.Airway contractions mediated by the endothelin (ET)A receptor,ETB receptor and M3 muscarinic receptor were augmented,and the augmented contraction was most obvious in lobar bronchi.The order of efficacy of contraction for lobar bronchi induced by agonists was ET-1,sarafotoxin 6c>ACh>5-HT.OX8 (an antibody against CD8+ T cells) strongly shifted and 0X35 (an antibody against CD4+ T cells) modestly shifted isoprenaline-induced concentration-relaxation curves in a nonparallel fashion to the left with an increased Rmax in asthmatic rats and sarafotoxin 6c-induced concentration-contractile curves to the right with a decreased Emax.Conclusion:The inhibition of airway relaxation and the augmentation of contraction mediated by receptors contribute to airway hyperresponsiveness and involve CD8+ and CD4+ T cells.

  20. Galangin Abrogates Ovalbumin-Induced Airway Inflammation via Negative Regulation of NF-κB

    Directory of Open Access Journals (Sweden)

    Wang-Jian Zha

    2013-01-01

    Full Text Available Persistent activation of nuclear factor κB (NF-κB has been associated with the development of asthma. Galangin, the active pharmacological ingredient from Alpinia galanga, is reported to have a variety of anti-inflammatory properties in vitro via negative regulation of NF-κB. This study aimed to investigate whether galangin can abrogate ovalbumin- (OVA- induced airway inflammation by negative regulation of NF-κB. BALB/c mice sensitized and challenged with OVA developed airway hyperresponsiveness (AHR and inflammation. Galangin dose dependently inhibited OVA-induced increases in total cell counts, eosinophil counts, and interleukin-(IL- 4, IL-5, and IL-13 levels in bronchoalveolar lavage fluid, and reduced serum level of OVA-specific IgE. Galangin also attenuated AHR, reduced eosinophil infiltration and goblet cell hyperplasia, and reduced expression of inducible nitric oxide synthase and vascular cell adhesion protein-1 (VCAM-1 levels in lung tissue. Additionally, galangin blocked inhibitor of κB degradation, phosphorylation of the p65 subunit of NF-κB, and p65 nuclear translocation from lung tissues of OVA-sensitized mice. Similarly, in normal human airway smooth muscle cells, galangin blocked tumor necrosis factor-α induced p65 nuclear translocation and expression of monocyte chemoattractant protein-1, eotaxin, CXCL10, and VCAM-1. These results suggest that galangin can attenuate ovalbumin-induced airway inflammation by inhibiting the NF-κB pathway.

  1. Therapeutic Effects of DNA Vaccine on Allergen-Induced Allergic Airway Inflammation in Mouse Model

    Institute of Scientific and Technical Information of China (English)

    Guoping Li; Zhigang Liu; Nanshan Zhong; Bin Liao1; Ying Xiong

    2006-01-01

    Vaccination with DNA encoding Dermatophagoides pteronyssinus group 2 (Der p 2) allergen previously showed its effects of immunologic protection on Der p 2 allergen-induced allergic airway inflammation in mice. In present study, we investigated whether DNA vaccine encoding Der p 2 could exert therapeutic role on allergen-induced allergic airway inflammation in mouse model and explored the mechanism of DNA vaccination in asthma specific-allergen immunotherapy. After sensitized and challenged by Der p 2, the BALB/c mice were immunized with DNA vaccine. The degrees of cellular infiltration were scored. IgE levels in serum and IL-4/lL-13 levels in BALF were determined by ELISA. The lung tissues were assessed by histological examinations. Expressions of STAT6 and NF-κB in lung were determined by immunohistochemistry staining. Vaccination of mice with DNA vaccine inhibited the development of airway inflammation and the production of mucin induced by allergen, and reduced the level of Der p 2-specific IgE level. Significant reductions of eosinophii infiltration and levels of IL-4and IL-13 in BALF were observed after vaccination. Further more, DNA vaccination inhibited STAT6 and NF-κBexpression in lung tissue in Der p 2-immunized mice. These results indicated that DNA vaccine encoding Der p 2allergen could be used for therapy of allergen-induced allergic airway inflammation in our mouse model.

  2. Iptakalim inhibits PDGF-BB-induced human airway smooth muscle cells proliferation and migration

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Wenrui; Kong, Hui; Zeng, Xiaoning; Wang, Jingjing; Wang, Zailiang; Yan, Xiaopei; Wang, Yanli; Xie, Weiping, E-mail: wpxie@njmu.edu.cn; Wang, Hong, E-mail: hongwang@njmu.edu.cn

    2015-08-15

    Chronic airway diseases are characterized by airway remodeling which is attributed partly to the proliferation and migration of airway smooth muscle cells (ASMCs). ATP-sensitive potassium (K{sub ATP}) channels have been identified in ASMCs. Mount evidence has suggested that K{sub ATP} channel openers can reduce airway hyperresponsiveness and alleviate airway remodeling. Opening K{sup +} channels triggers K{sup +} efflux, which leading to membrane hyperpolarization, preventing Ca{sup 2+}entry through closing voltage-operated Ca{sup 2+} channels. Intracellular Ca{sup 2+} is the most important regulator of muscle contraction, cell proliferation and migration. K{sup +} efflux decreases Ca{sup 2+} influx, which consequently influences ASMCs proliferation and migration. As a K{sub ATP} channel opener, iptakalim (Ipt) has been reported to restrain the proliferation of pulmonary arterial smooth muscle cells (PASMCs) involved in vascular remodeling, while little is known about its impact on ASMCs. The present study was designed to investigate the effects of Ipt on human ASMCs and the mechanisms underlying. Results obtained from cell counting kit-8 (CCK-8), flow cytometry and 5-ethynyl-2′-deoxyuridine (EdU) incorporation showed that Ipt significantly inhibited platelet-derived growth factor (PDGF)-BB-induced ASMCs proliferation. ASMCs migration induced by PDGF-BB was also suppressed by Ipt in transwell migration and scratch assay. Besides, the phosphorylation of Ca{sup 2+}/calmodulin-dependent kinase II (CaMKII), extracellular regulated protein kinases 1/2 (ERK1/2), protein kinase B (Akt), and cyclic adenosine monophosphate (cAMP) response element binding protein (CREB) were as well alleviated by Ipt administration. Furthermore, we found that the inhibition of Ipt on the PDGF-BB-induced proliferation and migration in human ASMCs was blocked by glibenclamide (Gli), a selective K{sub ATP} channel antagonist. These findings provide a strong evidence to support that Ipt

  3. [Anesthesia recovery comparison between remifentanil-propofol and remifentanil-desflurane guided by Bispectral Index(®) monitoring].

    Science.gov (United States)

    Rocha, Raphael Grossi; Almeida, Eduardo Giarola; Carneiro, Lara Moreira Mendes; Almeida, Natália Farias de; Boas, Walkíria Wingester Vilas; Gomez, Renato Santiago

    There is a strong demand for fast and predictable anesthesia recovery with few side effects. Choice of the hypnotic agent could impact on that. This study investigated the differences between recoveries after remifentanil-propofol and remifentanil-desflurane anesthesias guided by bispectral index (BIS(®)). Forty patients were randomly assigned into 2 groups according to the anesthesia technique applied: remifentanil-propofol (REM-PRO) and remifentanil-desflurane (REM-DES). After the discontinuation of the anesthetics, the times to extubation, to obey commands and to recover the airway protection reflex were recorted. In the post-anesthetic recovery room (PACU) it was recorded the occurrence of nausea and vomiting (PONV), scores of Ramsay sedation scale and of numeric pain scale (NPS), morphine dose and length of stay in the unit. Data from 38 patients were analyzed: 18 from REM-PRO and 20 from REM-DES group. Anesthesia times were similar (REM-PRO=193min, SD 79.9 vs. 175.7min, SD 87.9 REM-DES; p=0.5). REM-DES had shorter times than REM-PRO group: time to follow command (8.5min; SD 3.0 vs. 5.6min; SD 2.5; p=0.0) and extubation time (6.2 minutes; 3.1-8.5 vs. 9.5 minutes; 4.9-14.4; p=0.0). Times to recover airway protective reflex were similar: 16 patients from REM-PRO (88.9%) restored the airway protective reflex 2min after extubation vs. 17 from REM-DES (89.5%); and 2 patients from REM-PRO (11.1%) vs. 2 from REM-DES (10.5%) 6min after extubation, p=1. Ramsay sedation score, NPS, PONV incidents, morphine dose and PACU stay of length PACU were also similar. Remifentanil-desflurane-based anesthesia has a faster extubation time and to follow command than remifentanil-propofol-based anesthesia when both guided by BIS(®). Copyright © 2016 Sociedade Brasileira de Anestesiologia. Publicado por Elsevier Editora Ltda. All rights reserved.

  4. Exogenous irritant-induced airway hyperreactivity and inhibition of soluble guanylyl cyclase.

    Science.gov (United States)

    Antosová, Martina; Strapková, Anna; Turcan, Tomás

    2008-10-01

    The majority of nitric oxide (NO) effects in the respiratory system are caused by stimulation of soluble guanylyl cyclase (sGC) with subsequent increase of cyclic guanosine monophosphate (cGMP) production. The importance of this mechanism of NO action in airway hyperreactivity (AHR) pathogenesis is unknown. Therefore, the aim of our experiment was to examine the changes of airway reactivity enhanced by toluene vapor exposure in the presence or inhibition of sGC activity in guinea pigs. Animals were treated with a nonspecific sGC inhibitor, methylene blue, in a dose of 50 or 100 mg/kg body weight, administered by intraperitoneal injection 30 min before or after exposure to toluene vapors. The toluene exposure lasted 2 hr in each of 3 consecutive days under in vivo conditions. Thereafter, the tracheal and lung tissue smooth muscle response to cumulative doses of mediators (histamine or acetylcholine) was recorded under in vitro conditions. The exposure to toluene vapors significantly increased the airway reactivity to both mediators in comparison with the healthy animal group. The administration of methylene blue decreased the amplitude of airway smooth muscle contraction in toluene-induced hyperreactivity. The decreases were dependent on the inhibitor doses, on a regimen of administration (before or after toluene inhalation), the level of the respiratory system (trachea, lung), and the bronchoconstrictor mediators. Our results suggest that the interaction between NO and sGC may be important for airway reactivity changes, but other mechanisms of NO action are important in AHR pathogenesis, too.

  5. [Bronchomotoric in antigen induced airway obstruction (author's transl)].

    Science.gov (United States)

    Zimmermann, I; Ulmer, W T

    1977-01-01

    Ascaris suum extract inhalation causes bronchoconstriction in dogs. Following this reaction, the bronchi stay oversensitive against acetylcholine for at least 7 h. Electrical stimulation of the peripheral end of a nervus vagus after cutting supports the meaning that the bronchoconstriction will be caused mainly by challenge of sensory receptors. The reflex way runs through the nervus vagus. Sensitization of the bronchial tree means sensitization of the sensory receptors. Results of the arterial blood gases correspond to earlier results which showed two parts of the bronchial tree: the vagus-controlled part is mainly respnsible for the airway resistance, the vagus-noncontrolled part is mainly responsible for the regulation of the ventilation/perfusion relationships.

  6. Different regulation of cigarette smoke induced inflammation in upper versus lower airways

    Directory of Open Access Journals (Sweden)

    Bracke Ken R

    2010-07-01

    Full Text Available Abstract Background Cigarette smoke (CS is known to initiate a cascade of mediator release and accumulation of immune and inflammatory cells in the lower airways. We investigated and compared the effects of CS on upper and lower airways, in a mouse model of subacute and chronic CS exposure. Methods C57BL/6 mice were whole-body exposed to mainstream CS or air, for 2, 4 and 24 weeks. Bronchoalveolar lavage fluid (BAL was obtained and tissue cryosections from nasal turbinates were stained for neutrophils and T cells. Furthermore, we evaluated GCP-2, KC, MCP-1, MIP-3α, RORc, IL-17, FoxP3, and TGF-β1 in nasal turbinates and lungs by RT-PCR. Results In both upper and lower airways, subacute CS-exposure induced the expression of GCP-2, MCP-1, MIP-3α and resulted in a neutrophilic influx. However, after chronic CS-exposure, there was a significant downregulation of inflammation in the upper airways, while on the contrary, lower airway inflammation remained present. Whereas nasal FoxP3 mRNA levels already increased after 2 weeks, lung FoxP3 mRNA increased only after 4 weeks, suggesting that mechanisms to suppress inflammation occur earlier and are more efficient in nose than in lungs. Conclusions Altogether, these data demonstrate that CS induced inflammation may be differently regulated in the upper versus lower airways in mice. Furthermore, these data may help to identify new therapeutic targets in this disease model.

  7. Rhinovirus-induced Airway Cytokines and Respiratory Morbidity in Severely Premature Children

    Science.gov (United States)

    Perez, Geovanny F.; Pancham, Krishna; Huseni, Shehlanoor; Jain, Amisha; Rodriguez-Martinez, Carlos E.; Preciado, Diego; Rose, Mary C.; Nino, Gustavo

    2017-01-01

    Background Rhinovirus (RV) has been linked to the pathogenesis of asthma. Prematurity is a risk factor for severe RV infection in early life, but is unknown if RV elicits enhanced pro-asthmatic airway cytokine responses in premature infants. This study investigated if young children born severely premature (<32 weeks gestation) exhibit airway secretion of Th2 and Th17 cytokines during natural RV infections and if RV-induced Th2-Th17 responses are linked to more respiratory morbidity in premature children during the first two years of life. Methods We measured Th2 and Th17 nasal airway cytokines in a retrospective cohort of young children aged 0–2 years with PCR-confirmed RV infection or non-detectable virus. Protein levels of IL-4, IL-13, TSLP and IL-17 were determined with multiplex immunoassays. Demographic and clinical variables were obtained by electronic medical record (EMR) review. Results The study comprised 214 children born full term (n=108), pre-term (n=44) or severely premature (n=62). Natural RV infection in severely premature children was associated with elevated airway secretion of Th2 (IL-4 and IL-13) and Th17 (IL-17) cytokines, particularly in subjects with history of bronchopulmonary dysplasia. Severely premature children with high RV-induced airway IL-4 had recurrent respiratory hospitalizations (median 3.65 hosp/year; IQR 2.8–4.8) and were more likely to have at least one pediatric intensive care unit admission during the first two years of life (OR 8.72; 95% CI 1.3–58.7; p=0.02). Conclusions Severely premature children have increased airway secretion of Th2 and Th17 cytokines during RV infections, which is associated with more respiratory morbidity in the first two years of life PMID:25640734

  8. Effect of thromboxane antagonists on ozone-induced airway responses in dogs

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    Jones, G.L.; Lane, C.G.; O' Byrne, P.M. (McMaster Univ., Hamilton, Ontario (Canada))

    1990-09-01

    Airway hyperresponsiveness after inhaled ozone in dogs may occur as a result of thromboxane release in the airway. In this study, two thromboxane receptor antagonists, L-655,240 and L-670,596, were used in doses that inhibit the response to an inhaled thromboxane mimetic, U-46619, to determine further the role of thromboxane in ozone-induced airway hyperresponsiveness. Dogs were studied on 2 days separated by 1 wk. On each day, the dogs inhaled ozone (3 ppm) for 30 min. On one randomly assigned day, 10 dogs received an infusion of L-655,240 (5 mg.kg-1.h-1) and 5 dogs received an infusion of L-670,596 (1 mg.kg-1.h-1); on the other day dogs received a control infusion. Airway responses to doubling doses of acetylcholine were measured before and after inhalation of ozone and were expressed as the concentration of acetylcholine giving a rise in resistance of 5 cmH2O.l-1.s from baseline (acetylcholine provocation concentration). The development of airway hyperresponsiveness after ozone was not inhibited by the thromboxane antagonists. The mean log difference in the acetylcholine provocative concentration before and after ozone on the L-655,240 treatment day was 0.62 +/- 0.12 (SE) and on the control day was 0.71 +/- 0.12 (P = 0.48); on the L-670,596 treatment day the mean log difference was 0.68 +/- 0.15 (SE) and on the control day it was 0.75 +/- 0.19 (P = 0.45). These results do not support an important role for thromboxane in causing ozone-induced airway hyperresponsiveness.

  9. Time course of endotoxin-induced airways' inflammation in healthy subjects.

    Science.gov (United States)

    Doyen, Virginie; Kassengera, Zaina; Dinh, Duc Huy Phong; Michel, Olivier

    2012-02-01

    Few data are available on the kinetic of the airways' inflammation induced by inhaled endotoxin in a given subject. The purpose of this study was to evaluate in healthy subjects the time-related endotoxin-induced airways' inflammation. The cells counts from the induced-sputum were evaluated before, 6 and 24 h, and 7 days after an exposure to 20 mcg inhaled endotoxin, in eight pre-selected volunteers. To avoid interference of the induced-sputum procedure on the response to endotoxin, each time-point was evaluated in randomized order at 2-weeks interval after three separate inhalations of endotoxin. A significant rise of the relative number of lymphocytes (pinflammation after 6 h, peaked at 24 h and recovered after 7 days. When repeated endotoxin inhalations are used as a model of inflammation, a wash-out period of at least 7 days should be applied between each exposure in each subject.

  10. β2-Agonist induced cAMP is decreased in asthmatic airway smooth muscle due to increased PDE4D

    NARCIS (Netherlands)

    Trian, Thomas; Burgess, Janette K; Niimi, Kyoko; Moir, Lyn M; Ge, Qi; Berger, Patrick; Liggett, Stephen B; Black, Judith L; Oliver, Brian G

    2011-01-01

    BACKGROUND AND OBJECTIVE: Asthma is associated with airway narrowing in response to bronchoconstricting stimuli and increased airway smooth muscle (ASM) mass. In addition, some studies have suggested impaired β-agonist induced ASM relaxation in asthmatics, but the mechanism is not known. OBJECTIVE:

  11. TAK1 plays a major role in growth factor-induced phenotypic modulation of airway smooth muscle

    NARCIS (Netherlands)

    Pera, Tonio; Sami, Riham; Zaagsma, Johan; Meurs, Herman

    2011-01-01

    Pera T, Sami R, Zaagsma J, Meurs H. TAK1 plays a major role in growth factor-induced phenotypic modulation of airway smooth muscle. Am J Physiol Lung Cell Mol Physiol 301: L822-L828, 2011. First published August 26, 2011; doi:10.1152/ajplung.00017.2011.-Increased airway smooth muscle (ASM) mass is a

  12. Dexamethasone and N-acetyl-cysteine attenuate Pseudomonas aeruginosa-induced mucus expression in human airways.

    Science.gov (United States)

    Sprenger, Lisa; Goldmann, Torsten; Vollmer, Ekkehard; Steffen, Armin; Wollenberg, Barbara; Zabel, Peter; Hauber, Hans-Peter

    2011-04-01

    Infection with Pseudomonas aeruginosa (PA) induces mucus hypersecretion in airways. Therapeutic options to attenuate excessive mucus expression are sparse. To investigate the effect of steroids and N-acetyl-cysteine (NAC) on PA-induced mucus expression. Calu-3 cells and explanted human mucosa from the upper airways were stimulated with either PA, lipopolysaccharide from alginate producing PA (smooth, sPA-LPS) or non-alginate producing PA (rough, rPA-LPS). Dexamethasone (DEX) and NAC were added in different concentrations. Expression of mucin (MUC5AC) gene and mucin protein expression was quantified using PAS (periodic acids Schiff) staining and real time PCR. PA, sPA-LPS or rPA-LPS significantly induced mucin protein and MUC5AC gene expression in Calu-3 cells and explanted mucosal tissue (P NAC significantly decreased PA-, sPA-LPS- and rPA-LPS-induced mucin protein expression both in vitro and ex vivo (P 0.05). Our data show that both an anti-inflammatory drug (DEX) and an anti-oxidative agent (NAC) can attenuate PA-induced mucus expression in human airways. These results support the use of steroids and NAC in clinical practice to treat PA-induced mucus hypersecretion. Copyright © 2010 Elsevier Ltd. All rights reserved.

  13. Wogonin Attenuates Ovalbumin Antigen-Induced Neutrophilic Airway Inflammation by Inhibiting Th17 Differentiation

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    Rie Takagi

    2014-01-01

    Full Text Available Allergic airway inflammation is generally considered to be a Th2-type immune response. Recent studies, however, have demonstrated that Th17-type immune responses also play important roles in this process, particularly in the pathogenesis of neutrophilic airway inflammation, a hallmark of severe asthma. We scrutinized several Kampo extracts that reportedly exhibit anti-inflammatory activity by using in vitro differentiation system of human and mouse naïve T cells. We found that hange-shashin-to (HST and oren-gedoku-to (OGT possess inhibitory activity for Th17 responses in vitro. Indeed, wogonin and berberine, major components common to HST and OGT, exhibit Th17-inhibitory activities in both murine and human systems in vitro. We therefore evaluated whether wogonin suppresses OVA-induced neutrophilic airway inflammation in OVA TCR-transgenic DO11.10 mice. Consequently, oral administration of wogonin significantly improved OVA-induced neutrophilic airway inflammation. Wogonin suppressed the differentiation of naïve T cells to Th17 cells, while showing no effects on activated Th17 cells.

  14. Dexamethasone inhibits repair of human airway epithelial cells mediated by glucocorticoid-induced leucine zipper (GILZ.

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    Jingyue Liu

    Full Text Available BACKGROUND: Glucocorticoids (GCs are a first-line treatment for asthma for their anti-inflammatory effects, but they also hinder the repair of airway epithelial injury. The anti-inflammatory protein GC-induced leucine zipper (GILZ is reported to inhibit the activation of the mitogen-activated protein kinase (MAPK-extracellular-signal-regulated kinase (ERK signaling pathway, which promotes the repair of airway epithelial cells around the damaged areas. We investigated whether the inhibition of airway epithelial repair imposed by the GC dexamethasone (DEX is mediated by GILZ. METHODS: We tested the effect of DEX on the expressions of GILZ mRNA and GILZ protein and the MAPK-ERK signaling pathway in human airway epithelial cells, via RT-PCR and Western blot. We further evaluated the role of GILZ in mediating the effect of DEX on the MAPK-ERK signaling pathway and in airway epithelium repair by utilizing small-interfering RNAs, MTT, CFSE labeling, wound-healing and cell migration assays. RESULTS: DEX increased GILZ mRNA and GILZ protein levels in a human airway epithelial cell line. Furthermore, DEX inhibited the phosphorylation of Raf-1, Mek1/2, Erk1/2 (components of the MAPK-ERK signaling pathway, proliferation and migration. However, the inhibitory effect of DEX was mitigated in cells when the GILZ gene was silenced. CONCLUSIONS: The inhibition of epithelial injury repair by DEX is mediated in part by activation of GILZ, which suppressed activation of the MAPK-ERK signaling pathway, proliferation and migration. Our study implicates the involvement of DEX in this process, and furthers our understanding of the dual role of GCs.

  15. Inhibiting pollen reduced nicotinamide adenine dinucleotide phosphate oxidase–induced signal by intrapulmonary administration of antioxidants blocks allergic airway inflammation

    Science.gov (United States)

    Dharajiya, Nilesh; Choudhury, Barun K.; Bacsi, Attila; Boldogh, Istvan; Alam, Rafeul; Sur, Sanjiv

    2011-01-01

    Background Ragweed extract (RWE) contains NADPH oxidases that induce oxidative stress in the airways independent of adaptive immunity (signal 1) and augment antigen (signal 2)–induced allergic airway inflammation. Objective To test whether inhibiting signal 1 by administering antioxidants inhibits allergic airway inflammation in mice. Methods The ability of ascorbic acid (AA), N-acetyl cystenine (NAC), and tocopherol to scavenge pollen NADPH oxidase–generated reactive oxygen species (ROS) was measured. These antioxidants were administered locally to inhibit signal 1 in the airways of RWE-sensitized mice. Recruitment of inflammatory cells, mucin production, calcium-activated chloride channel 3, IL-4, and IL-13 mRNA expression was quantified in the lungs. Results Antioxidants inhibited ROS generation by pollen NADPH oxidases and intracellular ROS generation in cultured epithelial cells. AA in combination with NAC or Tocopherol decreased RWE-induced ROS levels in cultured bronchial epithelial cells. Coadministration of antioxidants with RWE challenge inhibited 4-hydroxynonenal adduct formation, upregulation of Clca3 and IL-4 in lungs, mucin production, recruitment of eosinophils, and total inflammatory cells into the airways. Administration of antioxidants with a second RWE challenge also inhibited airway inflammation. However, administration of AA+NAC 4 or 24 hours after RWE challenge failed to inhibit allergic inflammation. Conclusion Signal 1 plays a proinflammatory role during repeated exposure to pollen extract. We propose that inhibiting signal 1 by increasing antioxidant potential in the airways may be a novel therapeutic strategy to attenuate pollen-induced allergic airway inflammation. Clinical implications Administration of antioxidants in the airways may constitute a novel therapeutic strategy to prevent pollen induced allergic airway inflammation. PMID:17336614

  16. Dual p38/JNK mitogen activated protein kinase inhibitors prevent ozone-induced airway hyperreactivity in guinea pigs.

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    Kirsten C Verhein

    Full Text Available Ozone exposure causes airway hyperreactivity and increases hospitalizations resulting from pulmonary complications. Ozone reacts with the epithelial lining fluid and airway epithelium to produce reactive oxygen species and lipid peroxidation products, which then activate cell signaling pathways, including the mitogen activated protein kinase (MAPK pathway. Both p38 and c-Jun NH2 terminal kinase (JNK are MAPK family members that are activated by cellular stress and inflammation. To test the contribution of both p38 and JNK MAPK to ozone-induced airway hyperreactivity, guinea pigs were pretreated with dual p38 and JNK MAPK inhibitors (30 mg/kg, i.p. 60 minutes before exposure to 2 ppm ozone or filtered air for 4 hours. One day later airway reactivity was measured in anesthetized animals. Ozone caused airway hyperreactivity one day post-exposure, and blocking p38 and JNK MAPK completely prevented ozone-induced airway hyperreactivity. Blocking p38 and JNK MAPK also suppressed parasympathetic nerve activity in air exposed animals, suggesting p38 and JNK MAPK contribute to acetylcholine release by airway parasympathetic nerves. Ozone inhibited neuronal M2 muscarinic receptors and blocking both p38 and JNK prevented M2 receptor dysfunction. Neutrophil influx into bronchoalveolar lavage was not affected by MAPK inhibitors. Thus p38 and JNK MAPK mediate ozone-induced airway hyperreactivity through multiple mechanisms including prevention of neuronal M2 receptor dysfunction.

  17. Oroxylin A Inhibits Allergic Airway Inflammation in Ovalbumin (OVA)-Induced Asthma Murine Model.

    Science.gov (United States)

    Zhou, De-Gang; Diao, Bao-Zhong; Zhou, Wen; Feng, Jia-Long

    2016-04-01

    Oroxylin A, a natural flavonoid isolated from the medicinal herb Scutellaria baicalensis Georgi, has been reported to have anti-inflammatory property. In this study, we aimed to investigate the protective effects and mechanism of oroxylin A on allergic inflammation in OVA-induced asthma murine model. BABL/c mice were sensitized and airway-challenged with OVA to induce asthma. Oroxylin A (15, 30, and 60 mg/kg) was administered by oral gavage 1 h before the OVA treatment on day 21 to 23. The results showed that oroxylin A attenuated OVA-induced lung histopathologic changes, airway hyperresponsiveness, and the number of inflammatory cells. Oroxylin A also inhibited the levels of IL-4, IL-5, IL-13, and OVA-specific IgE in BALF. Furthermore, oroxylin A significantly inhibited OVA-induced NF-κB activation. In conclusion, these results suggested that oroxylin A inhibited airway inflammation in OVA-induced asthma murine model by inhibiting NF-κB activation. These results suggested that oroxylin A was a potential therapeutic drug for treating allergic asthma.

  18. Non-selective cation channels mediate chloroquine-induced relaxation in precontracted mouse airway smooth muscle.

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    Ting Zhang

    Full Text Available Bitter tastants can induce relaxation in precontracted airway smooth muscle by activating big-conductance potassium channels (BKs or by inactivating voltage-dependent L-type Ca2+ channels (VDLCCs. In this study, a new pathway for bitter tastant-induced relaxation was defined and investigated. We found nifedipine-insensitive and bitter tastant chloroquine-sensitive relaxation in epithelium-denuded mouse tracheal rings (TRs precontracted with acetylcholine (ACH. In the presence of nifedipine (10 µM, ACH induced cytosolic Ca2+ elevation and cell shortening in single airway smooth muscle cells (ASMCs, and these changes were inhibited by chloroquine. In TRs, ACH triggered a transient contraction under Ca2+-free conditions, and, following a restoration of Ca2+, a strong contraction occurred, which was inhibited by chloroquine. Moreover, the ACH-activated whole-cell and single channel currents of non-selective cation channels (NSCCs were blocked by chloroquine. Pyrazole 3 (Pyr3, an inhibitor of transient receptor potential C3 (TRPC3 channels, partially inhibited ACH-induced contraction, intracellular Ca2+ elevation, and NSCC currents. These results demonstrate that NSCCs play a role in bitter tastant-induced relaxation in precontracted airway smooth muscle.

  19. Effects of sevoflurane and desflurane on otoacoustic emissions in humans.

    Science.gov (United States)

    Gungor, Gurcan; Bozkurt-Sutas, Pervin; Gedik, Ozge; Atas, Ahmet; Babazade, Rovnat; Yilmaz, Mehmet

    2015-09-01

    Otoacoustic emissions (OAEs) are non-invasive, easy to apply and objective test methods which are widely used to determine the presence of hearing in audiology clinics. Under certain circumstances, the study should be applied under general anesthesia. The aim of this study was to determine the influence of new short-acting inhalation agents, desflurane and sevoflurane, on OAE in humans. These short-acting agents are widely used in general anesthesia. Thirty-one healthy patients who underwent septoplasty and turbinoplasty surgery were included in this study. Unpremedicated patients were anesthetized and monitored by a standard protocol except the inhalation agents. Desflurane and sevoflurane were added to the inhaled gas mixture at ~1MAC, 5-6 % and 1.5-2 %, respectively. Transient evoked otoacoustic emissions and distortion product otoacoustic emissions measured in both ears of each patient preoperatively in the operating room before induction, 5 min after induction, after the completion of surgical procedure while the anesthetic agents are still given and 1 h after surgery in the ward. Between-group and within-group comparisons and correlations with hemodynamic parameters were performed for statistical analysis. The measurements of 26 ears in desflurane group and 28 ears in sevoflurane group were evaluated. There were no differences in initial measurements between groups (p > 0.05). Both groups presented significant decrease in intraoperative measurements and changes in time were statistically significant (p blood pressures. Correlation between OAEs and systemic blood pressures were significant (p sevoflurane and desflurane decreased OAEs around 2-3 dB; OAEs are still measurable under inhalation agents. This provides some findings about the OAE status of patient, but the evaluations should be done with the impact of anesthetic agents in mind.

  20. Airways obstruction in asthmatics induced by body cooling.

    Science.gov (United States)

    Chen, W Y; Horton, D J

    1978-02-01

    Pulmonary and thermoregulatory reactions to body cooling were studied in eight asthmatic and five normal subjects. The cooling was achieved by a cold shower at water temperature (T) of 15 degrees C for 1 min, followed by exposing the wet body to a high wind generated by a fan for another minute. The skin T, oral T and pulmonary functions were measured before and after cooling. After the cooling, skin T fell a mean of 7 degrees in all subjects and the oral T fell 0.5 degrees in the normals and 0.7 degrees in the asthmatics. In asthmatics, the post-cooling forced expiratory volume in 1 s (FEV1) and maximal mid-expiratory flow (MMEF) fell significantly (P less than .05) to a mean of 79% and 72%of baseline, respectively, and thoracic gas volume (TGV) and airway resistance (Raw) increased significantly to 133% and 198% of baseline, respectively. In normal subjects a small but significant increase in Raw was found. No obstruction developed in the asthmatics after a warm shower at 37 degrees or after breathing the cold shower mist. It is suggested that it is body cooling which leads first to vasoconstriction and then cooling of respiratory mucosa that initiates bronchoconstriction in asthmatics.

  1. The effects of cannabidiol on the antigen-induced contraction of airways smooth muscle in the guinea-pig.

    Science.gov (United States)

    Dudášová, A; Keir, S D; Parsons, M E; Molleman, A; Page, C P

    2013-06-01

    (-)-Δ(9)-Tetrahydrocannabinol has been demonstrated to have beneficial effects in the airways, but its psychoactive effects preclude its therapeutic use for the treatment of airways diseases. In the present study we have investigated the effects of (-)-cannabidiol, a non-psychoactive component of cannabis for its actions on bronchial smooth muscle in vitro and in vivo. Guinea-pig bronchial smooth muscle contractions induced by exogenously applied spasmogens were measured isometrically. In addition, contractile responses of bronchial smooth muscle from ovalbumin-sensitized guinea-pigs were investigated in the absence or presence of (-)-cannabidiol. Furthermore, the effect of (-)-cannabidiol against ovalbumin-induced airway obstruction was investigated in vivo in ovalbumin-sensitized guinea-pigs. (-)-Cannabidiol did not influence the bronchial smooth muscle contraction induced by carbachol, histamine or neurokinin A. In contrast, (-)-cannabidiol inhibited anandamide- and virodhamine-induced responses of isolated bronchi. A fatty acid amide hydrolase inhibitor, phenylmethanesulfonyl fluoride reversed the inhibitory effect of (-)-cannabidiol on anandamide-induced contractions. In addition, (-)-cannabidiol inhibited the contractile response of bronchi obtained from allergic guinea-pigs induced by ovalbumin. In vivo, (-)-cannabidiol reduced ovalbumin-induced airway obstruction. In conclusion, our results suggest that cannabidiol can influence antigen-induced airway smooth muscle tone suggesting that this molecule may have beneficial effects in the treatment of obstructive airway disorders.

  2. Dietary Compound Kaempferol Inhibits Airway Thickening Induced by Allergic Reaction in a Bovine Serum Albumin-Induced Model of Asthma.

    Science.gov (United States)

    Shin, Daekeun; Park, Sin-Hye; Choi, Yean-Jung; Kim, Yun-Ho; Antika, Lucia Dwi; Habibah, Nurina Umy; Kang, Min-Kyung; Kang, Young-Hee

    2015-12-16

    Asthma is characterized by aberrant airways including epithelial thickening, goblet cell hyperplasia, and smooth muscle hypertrophy within the airway wall. The current study examined whether kaempferol inhibited mast cell degranulation and prostaglandin (PG) release leading to the development of aberrant airways, using an in vitro model of dinitrophenylated bovine serum albumin (DNP-BSA)-sensitized rat basophilic leukemia (RBL-2H3) mast cells and an in vivo model of BSA-challenged asthmatic mice. Nontoxic kaempferol at 10-20 μM suppressed β-hexosaminidase release and cyclooxygenase 2 (COX2)-mediated production of prostaglandin D2 (PGD2) and prostaglandin F2α (PGF2α) in sensitized mast cells. Oral administration of ≤20 mg/kg kaempferol blocked bovine serum albumin (BSA) inhalation-induced epithelial cell excrescence and smooth muscle hypertrophy by attenuating the induction of COX2 and the formation of PGD2 and PGF2α, together with reducing the anti-α-smooth muscle actin (α-SMA) expression in mouse airways. Kaempferol deterred the antigen-induced mast cell activation of cytosolic phospholipase A2 (cPLA2) responsive to protein kinase Cμ (PKCμ) and extracellular signal-regulated kinase (ERK). Furthermore, the antigen-challenged activation of Syk-phospholipase Cγ (PLCγ) pathway was dampened in kaempferol-supplemented mast cells. These results demonstrated that kaempferol inhibited airway wall thickening through disturbing Syk-PLCγ signaling and PKCμ-ERK-cPLA2-COX2 signaling in antigen-exposed mast cells. Thus, kaempferol may be a potent anti-allergic compound targeting allergic asthma typical of airway hyperplasia and hypertrophy.

  3. (--Epigallocatechin-3-gallate Reduces Cigarette Smoke-Induced Airway Neutrophilic Inflammation and Mucin Hypersecretion in Rats

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    Yingmin Liang

    2017-09-01

    Full Text Available Background: Cigarette smoking is the leading cause of chronic obstructive pulmonary disease. (--Epigallocatechin-3-gallate (EGCG, the major catechins in Chinese green tea, has been studied for its anti-oxidative and anti-inflammatory properties in cell and animal models. In this study, we aimed to analyze the effects of EGCG on cigarette smoke (CS-induced airway inflammation and mucus secretion in the CS-exposed rat model.Methods: Male Sprague-Dawley rats were randomly divided into either sham air (SA or CS exposure. EGCG (50 mg/kg b.wt. was given by oral gavage every other day in both SA and CS-exposed animals. Oxidative stress and inflammatory markers were determined in serum and/or bronchoalveolar lavage fluid by biochemical assays or ELISA. Lung morphological changes were examined by Periodic Acid-Schiff, Masson’s Trichrome staining and immunohistochemical analysis. Western blot analysis was performed to explore the effects of EGCG on epidermal growth factor receptor (EGFR-mediated signaling pathway.Results: (--Epigallocatechin-3-gallate treatment attenuated CS-induced oxidative stress, lung cytokine-induced neutrophil chemoattractant-1 release and neutrophil recruitment. CS exposure caused an increase in the number of goblet cells in line with MUC5AC upregulation, and increased lung collagen deposition, which were alleviated in the presence of EGCG. In addition, CS-induced phosphorylation of EGFR in rat lung was abrogated by EGCG treatment.Conclusion: (--Epigallocatechin-3-gallate treatment ameliorated CS-induced oxidative stress and neutrophilic inflammation, as well as airway mucus production and collagen deposition in rats. The present findings suggest that EGCG has a therapeutic effect on chronic airway inflammation and abnormal airway mucus production probably via inhibition of EGFR signaling pathway.

  4. The in vitro effect of desflurane preconditioning on endothelial adhesion molecules and mRNA expression.

    Science.gov (United States)

    Biao, Zhu; Zhanggang, Xue; Hao, Jiang; Changhong, Miao; Jing, Cang

    2005-04-01

    Lower expression of intercellular adhesion molecule-1 (ICAM-1), vascular adhesion molecule-1 (VCAM-1), and E-selectin may be responsible for attenuated ischemic-reperfusion neutrophil adhesion to vascular endothelium. Desflurane reduces ischemia-reperfusion injury. Therefore, we assessed whether desflurane affects the protein expression of ICAM-1 and E-selectin and mRNA expression of ICAM-1 and VCAM-1 of human umbilical venous endothelial cells (HUVEC) stimulated with tumor necrosis factor-alpha (TNF-alpha). HUVEC were preconditioned for 60 min with 1 minimum alveolar concentration desflurane before stimulating with TNF-alpha. Protein expression of adhesion molecules ICAM-1 and E-selectin of HUVEC were evaluated via immunocytochemical techniques combined with image cytometry. ICAM-1 and VCAM-1 mRNA expression of HUVEC were determined via reverse transcription-polymerase chain reaction. Desflurane not only reduced the protein expression of ICAM-1 and E-selectin but also ICAM-1 and VCAM-1 mRNA expression of the HUVEC. The adhesion rate of neutrophils with desflurane-treated HUVEC was slower. The decreased neutrophil adhesion on the desflurane-treated HUVEC correlated well with the decrease in adhesion molecule expression. These results show that desflurane affects the expression of adhesion molecules involved in the multistep process of neutrophil recruitment. Desflurane related ischemia-reperfusion injury reduction correlates well with expression inhibition of ICAM-1, VCAM-1, and E-selectin that mediates neutrophil rotation and firm adhesion on the vascular endothelium.

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

    Science.gov (United States)

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

    2010-12-01

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

  6. Chlamydophila pneumoniae induces a sustained airway hyperresponsiveness and inflammation in mice

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    Verweij Vivienne

    2007-11-01

    Full Text Available Abstract Background It has been reported that Chlamydophila (C. pneumoniae is involved in the initiation and promotion of asthma and chronic obstructive pulmonary diseases (COPD. Surprisingly, the effect of C. pneumoniae on airway function has never been investigated. Methods In this study, mice were inoculated intranasally with C. pneumoniae (strain AR39 on day 0 and experiments were performed on day 2, 7, 14 and 21. Results We found that from day 7, C. pneumoniae infection causes both a sustained airway hyperresponsiveness and an inflammation. Interferon-γ (IFN-γ and macrophage inflammatory chemokine-2 (MIP-2 levels in bronchoalveolar lavage (BAL-fluid were increased on all experimental days with exception of day 7 where MIP-2 concentrations dropped to control levels. In contrast, tumor necrosis factor-α (TNF-α levels were only increased on day 7. From day 7 to 21 epithelial damage and secretory cell hypertrophy was observed. It is suggested that, the inflammatory cells/mediators, the epithelial damage and secretory cell hypertrophy contribute to initiation of airway hyperresponsiveness. Conclusion Our study demonstrates for the first time that C. pneumoniae infection can modify bronchial responsiveness. This has clinical implications, since additional changes in airway responsiveness and inflammation-status induced by this bacterium may worsen and/or provoke breathlessness in asthma and COPD.

  7. Antibody to very late activation antigen 4 prevents interleukin-5-induced airway hyperresponsiveness and eosinophil infiltration in the airways of guinea pigs.

    Science.gov (United States)

    Kraneveld, A D; van Ark, I; Van Der Linde, H J; Fattah, D; Nijkamp, F P; Van Oosterhout, A J

    1997-08-01

    This study examines the effect of monoclonal antibody to very late activation antigen-4 (VLA-4) on IL5-induced airway hyperresponsiveness in vivo and eosinophil accumulation into guinea pig airways. IL5 has been shown to be important in the development of airway hyperresponsiveness and eosinophil accumulation in the guinea pig. Eosinophils, unlike neutrophils, express VLA-4 which mediates the adhesion to vascular cell adhesion molecule-1 on endothelial cells. Thus VLA-4 seems to be an important adhesion molecule in the infiltration of eosinophils from the vasculature into the airway tissue. In addition, it has been shown that IL5 activates VLA-4 on eosinophils to facilitate their adhesion. In the present study, IL5 (1 microg, twice on one day) or vehicle were administered intranasally. Monoclonal antibody (mAb) to VLA-4 (HP1/2) or the isotype-matched control mAb (1E6) were injected 1 hour before each IL5 or vehicle treatment at a dose of 2.5 mg/kg body weight. The next day in vivo bronchial reactivity, eosinophil number in bronchoalveolar lavage (BAL) fluid, and eosinophil peroxidase (EPO) activity in cell-free BAL fluid were determined. IL5 induces an increase in bronchial reactivity to histamine, which is associated with an accumulation of eosinophils into BAL fluid (control: 12 (5 to 42) x 10(5) cells and IL5: 69 (11 to 99) x 10(5) cells, p IL5. HP1/2 also suppresses the IL5-induced increase in EPO activity in cell-free BAL fluid. In conclusion, for the development of IL5-induced airway hyperresponsiveness in the guinea pig, the VLA-4-dependent infiltration and activation of eosinophils in the bronchial tissue seems to be essential.

  8. Role of EP2 and EP4 receptors in airway microvascular leak induced by prostaglandin E2.

    Science.gov (United States)

    Jones, Victoria C; Birrell, Mark A; Maher, Sarah A; Griffiths, Mark; Grace, Megan; O'Donnell, Valerie B; Clark, Stephen R; Belvisi, Maria G

    2016-03-01

    Airway microvascular leak (MVL) involves the extravasation of proteins from post-capillary venules into surrounding tissue. MVL is a cardinal sign of inflammation and an important feature of airway inflammatory diseases such as asthma. PGE2, a product of COX-mediated metabolism of arachidonic acid, binds to four receptors, termed EP1–4. PGE2 has a wide variety of effects within the airway, including modulation of inflammation, sensory nerve activation and airway tone. However, the effect of PGE2 on airway MVL and the receptor/s that mediate this have not been described. Evans Blue dye was used as a marker of airway MVL, and selective EP receptor agonists and antagonists were used alongside EP receptor-deficient mice to define the receptor subtype involved. PGE2 induced significant airway MVL in mice and guinea pigs. A significant reduction in PGE2-induced MVL was demonstrated in Ptger2−/− and Ptger4−/− mice and in wild-type mice pretreated simultaneously with EP2 (PF-04418948) and EP4 (ER-819762) receptor antagonists. In a model of allergic asthma, an increase in airway levels of PGE2 was associated with a rise in MVL; this change was absent in Ptger2−/− and Ptger4−/− mice. PGE2 is a key mediator produced by the lung and has widespread effects according to the EP receptor activated. Airway MVL represents a response to injury and under ‘disease’ conditions is a prominent feature of airway inflammation. The data presented highlight a key role for EP2 and EP4 receptors in MVL induced by PGE2.

  9. Bitter taste receptor agonists alter mitochondrial function and induce autophagy in airway smooth muscle cells.

    Science.gov (United States)

    Pan, Shi; Sharma, Pawan; Shah, Sushrut D; Deshpande, Deepak A

    2017-07-01

    Airway remodeling, including increased airway smooth muscle (ASM) mass, is a hallmark feature of asthma and COPD. We previously identified the expression of bitter taste receptors (TAS2Rs) on human ASM cells and demonstrated that known TAS2R agonists could promote ASM relaxation and bronchodilation and inhibit mitogen-induced ASM growth. In this study, we explored cellular mechanisms mediating the antimitogenic effect of TAS2R agonists on human ASM cells. Pretreatment of ASM cells with TAS2R agonists chloroquine and quinine resulted in inhibition of cell survival, which was largely reversed by bafilomycin A1, an autophagy inhibitor. Transmission electron microscope studies demonstrated the presence of double-membrane autophagosomes and deformed mitochondria. In ASM cells, TAS2R agonists decreased mitochondrial membrane potential and increased mitochondrial ROS and mitochondrial fragmentation. Inhibiting dynamin-like protein 1 (DLP1) reversed TAS2R agonist-induced mitochondrial membrane potential change and attenuated mitochondrial fragmentation and cell death. Furthermore, the expression of mitochondrial protein BCL2/adenovirus E1B 19-kDa protein-interacting protein 3 (Bnip3) and mitochondrial localization of DLP1 were significantly upregulated by TAS2R agonists. More importantly, inhibiting Bnip3 mitochondrial localization by dominant-negative Bnip3 significantly attenuated cell death induced by TAS2R agonist. Collectively the TAS2R agonists chloroquine and quinine modulate mitochondrial structure and function, resulting in ASM cell death. Furthermore, Bnip3 plays a central role in TAS2R agonist-induced ASM functional changes via a mitochondrial pathway. These findings further establish the cellular mechanisms of antimitogenic effects of TAS2R agonists and identify a novel class of receptors and pathways that can be targeted to mitigate airway remodeling as well as bronchoconstriction in obstructive airway diseases. Copyright © 2017 the American Physiological

  10. Aldose reductase regulates acrolein-induced cytotoxicity in human small airway epithelial cells.

    Science.gov (United States)

    Yadav, Umesh C S; Ramana, K V; Srivastava, Satish K

    2013-12-01

    Aldose reductase (AR), a glucose-metabolizing enzyme, reduces lipid aldehydes and their glutathione conjugates with more than 1000-fold efficiency (Km aldehydes 5-30 µM) relative to glucose. Acrolein, a major endogenous lipid peroxidation product as well as a component of environmental pollutants and cigarette smoke, is known to be involved in various pathologies including atherosclerosis, airway inflammation, COPD, and age-related disorders, but the mechanism of acrolein-induced cytotoxicity is not clearly understood. We have investigated the role of AR in acrolein-induced cytotoxicity in primary human small airway epithelial cells (SAECs). Exposure of SAECs to varying concentrations of acrolein caused cell death in a concentration- and time-dependent manner. AR inhibition by fidarestat prevented the low-dose (5-10 µM) but not the high-dose (>10 µM) acrolein-induced SAEC death. AR inhibition protected SAECs from low-dose (5 µM) acrolein-induced cellular reactive oxygen species (ROS). Inhibition of acrolein-induced apoptosis by fidarestat was confirmed by decreased condensation of nuclear chromatin, DNA fragmentation, comet tail moment, and annexin V fluorescence. Further, fidarestat inhibited acrolein-induced translocation of the proapoptotic proteins Bax and Bad from the cytosol to the mitochondria and that of Bcl2 and BclXL from the mitochondria to the cytosol. Acrolein-induced cytochrome c release from mitochondria was also prevented by AR inhibition. The mitogen-activated protein kinases (MAPKs), such as extracellular signal-regulated kinases 1 and 2, stress-activated protein kinase/c-Jun NH2-terminal kinase, and p38MAPK, and c-Jun were transiently activated in airway epithelial cells by acrolein in a concentration- and time-dependent fashion, which was significantly prevented by AR inhibition. These results suggest that AR inhibitors could prevent acrolein-induced cytotoxicity in the lung epithelial cells.

  11. Apigenin inhibits TGF-β1-induced proliferation and migration of airway smooth muscle cells.

    Science.gov (United States)

    Li, Li-Hua; Lu, Bin; Wu, Hong-Ke; Zhang, Hao; Yao, Fei-Fei

    2015-01-01

    It is well known that the proliferation and migration of ASM cells (ASMCs) plays an important role in the pathogenesis of airway remodeling in asthma. Previous studies reported that apigenin can inhibit airway remodeling in a mouse asthma model. However, its effects on the proliferation and migration of ASMCs in asthma remain unknown. Therefore, the aim of our present study was to investigate the effects of apigenin on ASMC proliferation and migration, and explore the possible molecular mechanism. We found that apigenin inhibited transforming growth factor-β1 (TGF-β1)-induced ASMC proliferation. The cell cycle was blocked at G1/S-interphase by apigenin. It also suppressed TGF-β1-induced ASMCs migration. Furthermore, apigenin inhibited TGF-β1-induced Smad 2 and Smad 3 phosphorylation in ASMCs. Taken together, these results suggested that apigenin inhibited the proliferation and migration of TGF-β1-stimulated ASMCs by inhibiting Smad signaling pathway. These data might provide useful information for treating asthma and show that apigenin has potential for attenuating airway remodeling.

  12. Effects of chronic intermittent hypoxia on allergen-induced airway inflammation in rats.

    Science.gov (United States)

    Broytman, Oleg; Braun, Rudolf K; Morgan, Barbara J; Pegelow, David F; Hsu, Pei-Ning; Mei, Linda S; Koya, Ajay K; Eldridge, Marlowe; Teodorescu, Mihaela

    2015-02-01

    Obstructive sleep apnea aggravates asthma, but its mechanisms are unknown. Chronic intermittent hypoxia is one hallmark feature of sleep apnea. In this study, we tested the effects of chronic intermittent hypoxia on allergen-induced inflammation in rats. Four groups (n = 9-11/group) of ovalbumin (OVA)-sensitized Brown-Norway rats underwent intermittent hypoxia (10% oxygen, 30 cycles/h, 10 h/d) or normoxia for 30 days concurrent with weekly OVA or vehicle challenges. Lung physiology, differential leukocyte counts from bronchoalveolar lavage, and histology (Picro Sirius Red staining for collagen content) were compared between groups 2 days after the last challenge. Gene expression in bronchoalveolar lavage cells was quantified by quantitative PCR. Compared with normoxia, chronic intermittent hypoxia reduced the FEV0.1/FVC ratio (P = 0.005), peak expiratory flow (P = 0.002), and mean midexpiratory flow (P = 0.004), predominantly in medium and large airways; decreased the baseline eosinophil number (P = 0.01) and amplified the effect of OVA on monocyte number (P = 0.02 for the interaction); in proximal airways, increased (P = 0.008), whereas in distal airways it decreased (P = 0.004), collagen density; induced qualitative emphysematous changes in lung periphery; and increased expression of the M2 macrophage marker YM-1 and augmented OVA-induced expression of plasminogen activator inhibitor-1. Chronic intermittent hypoxia alters immune response to allergen toward a more TH-1-predominant cellular phenotype with collagen deposition and matrix degradation, leading to airflow limitation. These findings highlight the potential of sleep apnea to aggravate airway dysfunction in patients with preexistent asthma.

  13. Chitin-Induced Airway Epithelial Cell Innate Immune Responses Are Inhibited by Carvacrol/Thymol.

    Science.gov (United States)

    Khosravi, Ali Reza; Erle, David J

    2016-01-01

    Chitin is produced in large amounts by fungi, insects, and other organisms and has been implicated in the pathogenesis of asthma. Airway epithelial cells are in direct contact with environmental particles and serve as the first line of defense against inhaled allergens and pathogens. The potential contributions of airway epithelial cells to chitin-induced asthma remain poorly understood. We hypothesized that chitin directly stimulates airway epithelial cells to release cytokines that promote type 2 immune responses and to induce expression of molecules which are important in innate immune responses. We found that chitin exposure rapidly induced the expression of three key type 2-promoting cytokines, IL-25, IL-33 and TSLP, in BEAS-2B transformed human bronchial epithelial cells and in A549 and H292 lung carcinoma cells. Chitin also induced the expression of the key pattern recognition receptors TLR2 and TLR4. Chitin induced the expression of miR-155, miR-146a and miR-21, each of which is known to up-regulate the expression of pro-inflammatory cytokines. Also the expression of SOCS1 and SHIP1 which are known targets of miR-155 was repressed by chitin treatment. The monoterpene phenol carvacrol (Car) and its isomer thymol (Thy) are found in herbal essential oils and have been shown to inhibit allergic inflammation in asthma models. We found that Car/Thy inhibited the effects of chitin on type 2-promoting cytokine release and on the expression of TLRs, SOCS1, SHIP1, and miRNAs. Car/Thy could also efficiently reduce the protein levels of TLR4, inhibit the increase in TLR2 protein levels in chitin plus Car/Thy-treated cells and increase the protein levels of SHIP1 and SOCS1, which are negative regulators of TLR-mediated inflammatory responses. We conclude that direct effects of chitin on airway epithelial cells are likely to contribute to allergic airway diseases like asthma, and that Car/Thy directly inhibits epithelial cell pro-inflammatory responses to chitin.

  14. Chitin-Induced Airway Epithelial Cell Innate Immune Responses Are Inhibited by Carvacrol/Thymol.

    Directory of Open Access Journals (Sweden)

    Ali Reza Khosravi

    Full Text Available Chitin is produced in large amounts by fungi, insects, and other organisms and has been implicated in the pathogenesis of asthma. Airway epithelial cells are in direct contact with environmental particles and serve as the first line of defense against inhaled allergens and pathogens. The potential contributions of airway epithelial cells to chitin-induced asthma remain poorly understood. We hypothesized that chitin directly stimulates airway epithelial cells to release cytokines that promote type 2 immune responses and to induce expression of molecules which are important in innate immune responses. We found that chitin exposure rapidly induced the expression of three key type 2-promoting cytokines, IL-25, IL-33 and TSLP, in BEAS-2B transformed human bronchial epithelial cells and in A549 and H292 lung carcinoma cells. Chitin also induced the expression of the key pattern recognition receptors TLR2 and TLR4. Chitin induced the expression of miR-155, miR-146a and miR-21, each of which is known to up-regulate the expression of pro-inflammatory cytokines. Also the expression of SOCS1 and SHIP1 which are known targets of miR-155 was repressed by chitin treatment. The monoterpene phenol carvacrol (Car and its isomer thymol (Thy are found in herbal essential oils and have been shown to inhibit allergic inflammation in asthma models. We found that Car/Thy inhibited the effects of chitin on type 2-promoting cytokine release and on the expression of TLRs, SOCS1, SHIP1, and miRNAs. Car/Thy could also efficiently reduce the protein levels of TLR4, inhibit the increase in TLR2 protein levels in chitin plus Car/Thy-treated cells and increase the protein levels of SHIP1 and SOCS1, which are negative regulators of TLR-mediated inflammatory responses. We conclude that direct effects of chitin on airway epithelial cells are likely to contribute to allergic airway diseases like asthma, and that Car/Thy directly inhibits epithelial cell pro-inflammatory responses

  15. Early treatment of chlorine-induced airway hyperresponsiveness and inflammation with corticosteroids

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    Jonasson, Sofia, E-mail: sofia.jonasson@foi.se [Swedish Defence Research Agency, Division of CBRN Defence and Security, Umeå (Sweden); Wigenstam, Elisabeth [Swedish Defence Research Agency, Division of CBRN Defence and Security, Umeå (Sweden); Department of Public Health and Clinical Medicine, Unit of Respiratory Medicine, Umeå University, Umeå (Sweden); Koch, Bo [Swedish Defence Research Agency, Division of CBRN Defence and Security, Umeå (Sweden); Bucht, Anders [Swedish Defence Research Agency, Division of CBRN Defence and Security, Umeå (Sweden); Department of Public Health and Clinical Medicine, Unit of Respiratory Medicine, Umeå University, Umeå (Sweden)

    2013-09-01

    Chlorine (Cl{sub 2}) is an industrial gas that is highly toxic and irritating when inhaled causing tissue damage and an acute inflammatory response in the airways followed by a long-term airway dysfunction. The aim of this study was to evaluate whether early anti-inflammatory treatment can protect against the delayed symptoms in Cl{sub 2}-exposed mice. BALB/c mice were exposed by nose-only inhalation using 200 ppm Cl{sub 2} during 15 min. Assessment of airway hyperresponsiveness (AHR), inflammatory cell counts in bronchoalveolar lavage, occurrence of lung edema and lung fibrosis were analyzed 24 h or 14 days post-exposure. A single dose of the corticosteroid dexamethasone (10 or 100 mg/kg) was administered intraperitoneally 1, 3, 6, or 12 h following Cl{sub 2} exposure. High-dose of dexamethasone reduced the acute inflammation if administered within 6 h after exposure but treated animals still displayed a significant lung injury. The effect of dexamethasone administered within 1 h was dose-dependent; high-dose significantly reduced acute airway inflammation (100 mg/kg) but not treatment with the relatively low-dose (10 mg/kg). Both doses reduced AHR 14 days later, while lung fibrosis measured as collagen deposition was not significantly reduced. The results point out that the acute inflammation in the lungs due to Cl{sub 2} exposure only partly is associated with the long-term AHR. We hypothesize that additional pathogenic mechanisms apart from the inflammatory reactions contribute to the development of long-term airway dysfunction. By using this mouse model, we have validated early administration of corticosteroids in terms of efficacy to prevent acute lung injury and delayed symptoms induced by Cl{sub 2} exposure. - Highlights: • Inhalation of Cl{sub 2} may lead to a long-standing airway hyperresponsiveness. • The symptoms in Cl{sub 2}-exposed mice are similar to those described for RADS in humans. • Corticosteroids prevent delayed symptoms such as AHR in

  16. Inhibitory Effect of Sihuangxiechai Decoction on Ovalbumin-Induced Airway Inflammation in Guinea Pigs

    Directory of Open Access Journals (Sweden)

    Xue Ping Huang

    2014-01-01

    Full Text Available The aim of this study was to investigate the effect of sihuangxiechai decoction on asthmatic Guinea pig model which was sensitized by intraperitoneal (i.p. injection of ovalbumin (OVA and challenged by OVA inhalation to induce chronic airway inflammation. Differential cell counts of cytospins were performed after staining with Giemsa solution. The quantity of leukocytes and its classification in bronchoalveolar lavage fluid (BALF and blood were evaluated by blood cell analyzer and microscope. Histological analysis of the lung was performed by hematoxylin and eosin (H&E staining. The levels of interleukin-4 (IL-4 and tumor necrosis factor-alpha (TNF-α in BALF and serum were detected by radioimmunoassay (RIA. The total number of leukocytes in BALF and blood has no significant difference between Sihuangxiechaitang decoction treated group and dexamethasone (DXM treated group but was significantly lower than those of asthma group. The percentage of eosinophils in lung tissues of sihuangxiechai decoction treated group was significantly lower than that of asthma group. The results demonstrated that the levels of IL-4 and TNF-α in the sihuangxiechai decoction treated group were significantly reduced compared with the asthma group. In conclusion, these findings demonstrate that sihuangxiechai decoction has a protective effect on OVA-induced asthma in reducing airway inflammation and airway hyperresponsiveness (AHR in a Guinea pig model and may be useful as an adjuvant therapy for the treatment of bronchial asthma.

  17. Pulmonary Stress Induced by Hyperthermia: Role of Airway Sensory Nerves

    Science.gov (United States)

    2016-01-01

    support of our hypothesis that the stress of hyperthermia exerted on the respiratory system is primarily mediated through an activation of the...N. Activation of an epithelial neurokinin NK-1 receptor induces relaxation of rat trachea through release of prostaglandin E2. J Pharmacol Exp Ther...inspiratory duty cycle, shortened expiratory time, and reduced expiratory activity . All these effects stress the inspiratory muscles, resulting inspira

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

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    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.

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

    Science.gov (United States)

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

    2013-09-01

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

  20. LF-15 & T7, synthetic peptides derived from tumstatin, attenuate aspects of airway remodelling in a murine model of chronic OVA-induced allergic airway disease.

    Directory of Open Access Journals (Sweden)

    Karryn T Grafton

    Full Text Available BACKGROUND: Tumstatin is a segment of the collagen-IV protein that is markedly reduced in the airways of asthmatics. Tumstatin can play an important role in the development of airway remodelling associated with asthma due to its anti-angiogenic properties. This study assessed the anti-angiogenic properties of smaller peptides derived from tumstatin, which contain the interface tumstatin uses to interact with the αVβ3 integrin. METHODS: Primary human lung endothelial cells were exposed to the LF-15, T3 and T7 tumstatin-derived peptides and assessed for cell viability and tube formation in vitro. The impact of the anti-angiogenic properties on airways hyperresponsiveness (AHR was then examined using a murine model of chronic OVA-induced allergic airways disease. RESULTS: The LF-15 and T7 peptides significantly reduced endothelial cell viability and attenuated tube formation in vitro. Mice exposed to OVA+ LF-15 or OVA+T7 also had reduced total lung vascularity and AHR was attenuated compared to mice exposed to OVA alone. T3 peptides reduced cell viability but had no effect on any other parameters. CONCLUSION: The LF-15 and T7 peptides may be appropriate candidates for use as novel pharmacotherapies due to their small size and anti-angiogenic properties observed in vitro and in vivo.

  1. Hyaluronic acid influence on platelet-induced airway smooth muscle cell proliferation

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    Svensson Holm, Ann-Charlotte B., E-mail: ann-charlotte.svensson@liu.se [Division of Drug Research/Pharmacology, Department of Medical and Health Sciences, Faculty of Health Sciences, Linkoeping University, SE-581 85 Linkoeping (Sweden); Experimental Pathology, Department of Clinical and Experimental Medicine, Linkoeping University, SE-581 85 Linkoeping (Sweden); Bengtsson, Torbjoern [Department of Biomedicine, School of Health and Medical Sciences, Oerebro University, SE-70182 Oerebro (Sweden); Grenegard, Magnus; Lindstroem, Eva G. [Division of Drug Research/Pharmacology, Department of Medical and Health Sciences, Faculty of Health Sciences, Linkoeping University, SE-581 85 Linkoeping (Sweden)

    2012-03-10

    Hyaluronic acid (HA) is one of the main components of the extracellular matrix (ECM) and is expressed throughout the body including the lung and mostly in areas surrounding proliferating and migrating cells. Furthermore, platelets have been implicated as important players in the airway remodelling process, e.g. due to their ability to induce airway smooth muscle cell (ASMC) proliferation. The aim of the present study was to investigate the role of HA, the HA-binding surface receptor CD44 and focal adhesion kinase (FAK) in platelet-induced ASMC proliferation. Proliferation of ASMC was measured using the MTS-assay, and we found that the CD44 blocking antibody and the HA synthase inhibitor 4-Methylumbelliferone (4-MU) significantly inhibited platelet-induced ASMC proliferation. The interaction between ASMC and platelets was studied by fluorescent staining of F-actin. In addition, the ability of ASMC to synthesise HA was investigated by fluorescent staining using biotinylated HA-binding protein and a streptavidin conjugate. We observed that ASMC produced HA and that a CD44 blocking antibody and 4-MU significantly inhibited platelet binding to the area surrounding the ASMC. Furthermore, the FAK-inhibitor PF 573228 inhibited platelet-induced ASMC proliferation. Co-culture of ASMC and platelets also resulted in increased phosphorylation of FAK as detected by Western blot analysis. In addition, 4-MU significantly inhibited the increased FAK-phosphorylation. In conclusion, our findings demonstrate that ECM has the ability to influence platelet-induced ASMC proliferation. Specifically, we propose that HA produced by ASMC is recognised by platelet CD44. The platelet/HA interaction is followed by FAK activation and increased proliferation of co-cultured ASMC. We also suggest that the mitogenic effect of platelets represents a potential important and novel mechanism that may contribute to airway remodelling.

  2. Caveolin-1: Functional Insights into Its Role in Muscarine- and Serotonin-Induced Smooth Muscle Constriction in Murine Airways

    Directory of Open Access Journals (Sweden)

    Maryam Keshavarz

    2017-05-01

    Full Text Available An increased bronchoconstrictor response is a hallmark in the progression of obstructive airway diseases. Acetylcholine and 5-hydroxytryptamine (5-HT, serotonin are the major bronchoconstrictors. There is evidence that both cholinergic and serotonergic signaling in airway smooth muscle (ASM involve caveolae. We hypothesized that caveolin-1 (cav-1, a structural protein of caveolae, plays an important regulatory role in ASM contraction. We analyzed airway contraction in different tracheal segments and extra- and intrapulmonary bronchi in cav-1 deficient (cav-1−/− and wild-type mice using organ bath recordings and videomorphometry of methyl-beta-cyclodextrin (MCD treated and non-treated precision-cut lung slices (PCLS. The presence of caveolae was investigated by electron microscopy. Receptor subtypes driving 5-HT-responses were studied by RT-PCR and videomorphometry after pharmacological inhibition with ketanserin. Cav-1 was present in tracheal epithelium and ASM. Muscarine induced a dose dependent contraction in all airway segments. A significantly higher Emax was observed in the caudal trachea. Although, caveolae abundancy was largely reduced in cav-1−/− mice, muscarine-induced airway contraction was maintained, albeit at diminished potency in the middle trachea, in the caudal trachea and in the bronchus without changes in the maximum efficacy. MCD-treatment of PLCS from cav-1−/− mice reduced cholinergic constriction by about 50%, indicating that cholesterol-rich plasma domains account for a substantial portion of the muscarine-induced bronchoconstriction. Notably, cav-1-deficiency fully abrogated 5-HT-induced contraction of extrapulmonary airways. In contrast, 5-HT-induced bronchoconstriction was fully maintained in cav-1-deficient intrapulmonary bronchi, but desensitization upon repetitive stimulation was enhanced. RT-PCR analysis revealed 5-HT1B, 5-HT2A, 5-HT6, and 5-HT7 receptors as the most prevalent subtypes in the airways. The

  3. Retinoic acid prevents virus-induced airway hyperreactivity and M2 receptor dysfunction via anti-inflammatory and antiviral effects

    OpenAIRE

    Moreno-Vinasco, Liliana; Verbout, Norah G.; Fryer, Allison D.; Jacoby, David B.

    2009-01-01

    Inhibitory M2 muscarinic receptors on airway parasympathetic nerves normally limit acetylcholine release. Viral infections decrease M2 receptor function, increasing vagally mediated bronchoconstriction. Since retinoic acid deficiency causes M2 receptor dysfunction, we tested whether retinoic acid would prevent virus-induced airway hyperreactivity and prevent M2 receptor dysfunction. Guinea pigs infected with parainfluenza virus were hyperreactive to electrical stimulation of the vagus nerves,...

  4. Duration effect of desflurane anesthesia and its awakening time and arterial concentration in gynecologic patients

    Directory of Open Access Journals (Sweden)

    Tso-Chou Lin

    2013-10-01

    Full Text Available OBJECTIVES: To determine the awakening arterial blood concentration of desflurane and its relationship with the end-tidal concentration during emergence from various durations of general anesthesia. METHOD: In total, 42 American Society of Anesthesiologists physical status class I-II female patients undergoing elective gynecologic surgery were enrolled. General anesthesia was maintained with fixed 6% inspiratory desflurane in 6 l min-1 oxygen until shutoff of the vaporizer at the end of surgery. One milliliter of arterial blood was obtained for desflurane concentration determination by gas chromatography at 20 and 10 minutes before and 0, 5, 10, 15, and 20 minutes after the discontinuation of desflurane and at the time of eye opening upon verbal command, defined as awakening. Concentrations of inspiratory and end-tidal desflurane were simultaneously detected by an infrared analyzer. RESULTS: The mean arterial blood concentration of desflurane was 1.20% at awakening, which correlated with the awakening end-tidal concentration of 0.96%. The mean time from the discontinuation of desflurane to eye opening was 5.2 minutes (SD = 1.6, range 3-10, which was not associated with the duration of anesthesia (60-256 minutes, total fentanyl dose, or body mass index (BMI. CONCLUSIONS: The mean awakening arterial blood concentration of desflurane was 1.20%. The time to awakening was independent of anesthetic duration within four hours. Using well-assisted ventilation, the end-tidal concentration of desflurane was proven to represent the arterial blood concentration during elimination and could be a clinically feasible predictor of emergence from general anesthesia.

  5. Analysis of airway secretions in a model of sulfur dioxide induced chronic obstructive pulmonary disease (COPD

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    Fischer Axel

    2006-06-01

    Full Text Available Abstract Hypersecretion and chronic phlegm are major symptoms of chronic obstructive pulmonary disease (COPD but animal models of COPD with a defined functional hypersecretion have not been established so far. To identify an animal model of combined morphological signs of airway inflammation and functional hypersecretion, rats were continuously exposed to different levels of sulfur dioxide (SO2, 5 ppm, 10 ppm, 20 ppm, 40 ppm, 80 ppm for 3 (short-term or 20–25 (long-term days. Histology revealed a dose-dependent increase in edema formation and inflammatory cell infiltration in short-term-exposed animals. The submucosal edema was replaced by fibrosis after long-term-exposure. The basal secretory activity was only significantly increased in the 20 ppm group. Also, stimulated secretion was significantly increased only after exposure to 20 ppm. BrdU-assays and AgNOR-analysis demonstrated cellular metaplasia and glandular hypertrophy rather than hyperplasia as the underlying morphological correlate of the hypersecretion. In summary, SO2-exposure can lead to characteristic airway remodeling and changes in mucus secretion in rats. As only long-term exposure to 20 ppm leads to a combination of hypersecretion and airway inflammation, only this mode of exposure should be used to mimic human COPD. Concentrations less or higher than 20 ppm or short term exposure do not induce the respiratory symptom of hypersecretion. The present model may be used to characterize the effects of new compounds on mucus secretion in the background of experimental COPD.

  6. Interleukin-12 suppresses filaria-induced pulmonary eosinophilia, deposition of major basic protein and airway hyperresponsiveness.

    Science.gov (United States)

    Mehlotra, R K; Hall, L R; Higgins, A W; Dreshaj, I A; Haxhiu, M A; Kazura, J W; Pearlman, E

    1998-10-01

    Tropical Pulmonary Eosinophilia (TPE) is a severe form of allergic asthma caused by the host inflammatory response to filarial helminths in the lung microvasculature, and is characterized by pulmonary eosinophilia, increased filarial-specific IgG and IgE antibodies, and airway hyperresponsiveness. The current study examined the effect of IL-12 on pulmonary eosinophilia, deposition of eosinophil major basic protein and airway hyperresponsiveness in mice inoculated i.v. with Brugia malayi microfilariae. Injection of recombinant murine IL-12 modulated the T helper (Th) response in the lungs from Th2- to Th1-like, with elevated IFN-gamma, and decreased IL-4 and IL-5 production. Consistent with this shift in cytokine response, antigen-specific IgG2a was elevated, and IgG1 and total serum IgE were decreased. In addition, eosinophils in BAL fluid from IL-12 treated mice were reduced from 56% to 11%, and there was no detectable MBP on respiratory epithelial cells. Importantly, IL-12 suppressed airway hyperresponsiveness compared with saline-injected control animals. Taken together, these data clearly demonstrate that by modulating Th associated cytokine production, IL-12 down-regulates filaria-induced lung immunopathology.

  7. Triptolide inhibits TGF-β1-induced cell proliferation in rat airway smooth muscle cells by suppressing Smad signaling

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Ming; Lv, Zhiqiang; Huang, Linjie [Department of Respiratory Medicine, Sun Yat-Sen Memorial Hospital, Institute for Respiratory disease of Sun Yat-sen University, Sun Yat-sen University, Guangzhou, Guangdong Province 510120 (China); Zhang, Wei [Department of Geratology, the Second People' s Hospital of Shenzhen, Shenzhen 518000 (China); Lin, Xiaoling; Shi, Jianting; Zhang, Wei; Liang, Ruiyun [Department of Respiratory Medicine, Sun Yat-Sen Memorial Hospital, Institute for Respiratory disease of Sun Yat-sen University, Sun Yat-sen University, Guangzhou, Guangdong Province 510120 (China); Jiang, Shanping, E-mail: shanpingjiang@126.com [Department of Respiratory Medicine, Sun Yat-Sen Memorial Hospital, Institute for Respiratory disease of Sun Yat-sen University, Sun Yat-sen University, Guangzhou, Guangdong Province 510120 (China)

    2015-02-15

    Background: We have reported that triptolide can inhibit airway remodeling in a murine model of asthma via TGF-β1/Smad signaling. In the present study, we aimed to investigate the effect of triptolide on airway smooth muscle cells (ASMCs) proliferation and the possible mechanism. Methods: Rat airway smooth muscle cells were cultured and made synchronized, then pretreated with different concentration of triptolide before stimulated by TGF-β1. Cell proliferation was evaluated by MTT assay. Flow cytometry was used to study the influence of triptolide on cell cycle and apoptosis. Signal proteins (Smad2, Smad3 and Smad7) were detected by western blotting analysis. Results: Triptolide significantly inhibited TGF-β1-induced ASMC proliferation (P<0.05). The cell cycle was blocked at G1/S-interphase by triptolide dose dependently. No pro-apoptotic effects were detected under the concentration of triptolide we used. Western blotting analysis showed TGF-β1 induced Smad2 and Smad3 phosphorylation was inhibited by triptolide pretreatment, and the level of Smad7 was increased by triptolide pretreatment. Conclusions: Triptolide may function as an inhibitor of asthma airway remodeling by suppressing ASMCs proliferation via negative regulation of Smad signaling pathway. - Highlights: • In this study, rat airway smooth muscle cells were cultured and made synchronized. • Triptolide inhibited TGF-β1-induced airway smooth muscle cells proliferation. • Triptolide inhibited ASMCs proliferation via negative regulation of Smad signaling pathway.

  8. Parainfluenza 3-Induced Cough Hypersensitivity in the Guinea Pig Airways.

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    Eric J Zaccone

    Full Text Available The effect of respiratory tract viral infection on evoked cough in guinea pigs was evaluated. Guinea pigs were inoculated intranasally with either parainfluenza type 3 (PIV3 and cough was quantified in conscious animals. The guinea pigs infected with PIV3 (day 4 coughed nearly three times more than those treated with the viral growth medium in response to capsaicin, citric acid, and bradykinin. Since capsaicin, citric acid, and bradykinin evoked coughing in guinea pigs can be inhibited by drugs that antagonize the transient receptor potential cation channel, subfamily V, member 1 (TRPV1, it was reasoned that the virally-induced hypertussive state may involve alterations in TPRV1 activity. PIV3 infection caused a phenotypic switch in tracheal nodose Aδ "cough receptors" such that nearly 50% of neurons began to express, de novo, TRPV1 mRNA. There was also an increase TRPV1 expression in jugular C-fiber neurons as determined by qPCR. It has previously been reported that tracheal-specific nodose neurons express the BDNF receptor TrkB and jugular neurons express the NGF receptor TrkA. Jugular neurons also express the artemin receptor GFRα3. All these neurotrophic factors have been associated with increases in TRPV1 expression. In an ex vivo perfused guinea pig tracheal preparation, we demonstrated that within 8 h of PIV3 infusion there was no change in NGF mRNA expression, but there was nearly a 10-fold increase in BDNF mRNA in the tissue, and a small but significant elevation in the expression of artemin mRNA. In summary, PIV3 infection leads to elevations in TRPV1 expression in the two key cough evoking nerve subtypes in the guinea pig trachea, and this is associated with a hypertussive state with respect to various TRPV1 activating stimuli.

  9. TRPC3-mediated Ca(2+) entry contributes to mouse airway smooth muscle cell proliferation induced by lipopolysaccharide.

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    Chen, Xiao-Xu; Zhang, Jia-Hua; Pan, Bin-Hua; Ren, Hui-Li; Feng, Xiu-Ling; Wang, Jia-Ling; Xiao, Jun-Hua

    2016-10-01

    Airway remodeling is a histopathological hallmark of chronic respiratory diseases that includes airway smooth muscle cell (ASMC) proliferation. Canonical transient receptor potential channel-3 (TRPC3)-encoded nonselective cation channels (NSCCs) are important native constitutively active channels that play significant roles in physiological and pathological conditions in ASMCs. Lipopolysaccharides (LPSs), known as lipoglycans and endotoxin, have been proven to be inducers of airway remodeling, though the mechanisms remain unclear. We hypothesized that TRPC3 is important in LPS-induced airway remodeling by regulating ASMC proliferation. To test this hypothesis, mouse ASMCs were cultured with or without LPS for 48h. Cell viability, TRPC3 protein expression, NSCC currents and changes in intracellular calcium concentration ([Ca(2+)]i) were then analyzed using an MTT assay, western blotting, whole-cell patch clamp and calcium imaging, respectively. The results showed that LPS treatment significantly induced ASMC proliferation, up-regulation of TRPC3 protein expression and enhancement of NSCC currents, resting [Ca(2+)]i and ACh-elicited changes in [Ca(2+)]i. TRPC3 blocker Gd(3+), TRPC3 blocking antibody or TRPC3 gene silencing by siRNA significantly inhibited LPS-induced up-regulation of TRPC3 protein, enhancement of NSCC currents, resting [Ca(2+)]i and ACh-elicited changes in [Ca(2+)]i, eventually inhibiting LPS-induced ASMCproliferation. These results demonstrated that TRPC3-mediated Ca(2+) entry contributed to LPS-induced ASMC proliferation and identified TRPC3 as a possible key target in airway remodeling intervention.

  10. Preventive Intra Oral Treatment of Sea Cucumber Ameliorate OVA-Induced Allergic Airway Inflammation.

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    Lee, Da-In; Park, Mi-Kyung; Kang, Shin Ae; Choi, Jun-Ho; Kang, Seok-Jung; Lee, Jeong-Yeol; Yu, Hak Sun

    2016-01-01

    Sea cucumber extracts have potent biological effects, including anti-viral, anti-cancer, antibacterial, anti-oxidant, and anti-inflammation effects. To understand their anti-asthma effects, we induced allergic airway inflammation in mice after 7 oral administrations of the extract. The hyper-responsiveness value in mice with ovalbumin (OVA)-alum-induced asthma after oral injection of sea cucumber extracts was significantly lower than that in the OVA-alum-induced asthma group. In addition, the number of eosinophils in the lungs of asthma-induced mice pre-treated with sea cucumber extract was significantly decreased compared to that of PBS pre-treated mice. Additionally, CD4[Formula: see text]CD25[Formula: see text]Foxp3[Formula: see text]T (regulatory T; Treg) cells significantly increased in mesenteric lymph nodes after 7 administrations of the extract. These results suggest that sea cucumber extract can ameliorate allergic airway inflammation via Treg cell activation and recruitment to the lung.

  11. Metformin prevents the effects of Pseudomonas aeruginosa on airway epithelial tight junctions and restricts hyperglycaemia-induced bacterial growth.

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    Patkee, Wishwanath R A; Carr, Georgina; Baker, Emma H; Baines, Deborah L; Garnett, James P

    2016-04-01

    Lung disease and elevation of blood glucose are associated with increased glucose concentration in the airway surface liquid (ASL). Raised ASL glucose is associated with increased susceptibility to infection by respiratory pathogens including Staphylococcus aureus and Pseudomonas aeruginosa. We have previously shown that the anti-diabetes drug, metformin, reduces glucose-induced S. aureus growth across in vitro airway epithelial cultures. The aim of this study was to investigate whether metformin has the potential to reduce glucose-induced P. aeruginosa infections across airway epithelial (Calu-3) cultures by limiting glucose permeability. We also explored the effect of P. aeruginosa and metformin on airway epithelial barrier function by investigating changes in tight junction protein abundance. Apical P. aeruginosa growth increased with basolateral glucose concentration, reduced transepithelial electrical resistance (TEER) and increased paracellular glucose flux. Metformin pre-treatment of the epithelium inhibited the glucose-induced growth of P. aeruginosa, increased TEER and decreased glucose flux. Similar effects on bacterial growth and TEER were observed with the AMP activated protein kinase agonist, 5-aminoimidazole-4-carboxamide ribonucleotide. Interestingly, metformin was able to prevent the P. aeruginosa-induced reduction in the abundance of tight junction proteins, claudin-1 and occludin. Our study highlights the potential of metformin to reduce hyperglycaemia-induced P. aeruginosa growth through airway epithelial tight junction modulation, and that claudin-1 and occludin could be important targets to regulate glucose permeability across airway epithelia and supress bacterial growth. Further investigation into the mechanisms regulating metformin and P. aeruginosa action on airway epithelial tight junctions could yield new therapeutic targets to prevent/suppress hyperglycaemia-induced respiratory infections, avoiding the use of antibiotics.

  12. Extra-cellular matrix proteins induce matrix metalloproteinase-1 (MMP-1 activity and increase airway smooth muscle contraction in asthma.

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    Natasha K Rogers

    Full Text Available Airway remodelling describes the histopathological changes leading to fixed airway obstruction in patients with asthma and includes extra-cellular matrix (ECM deposition. Matrix metalloproteinase-1 (MMP-1 is present in remodelled airways but its relationship with ECM proteins and the resulting functional consequences are unknown. We used airway smooth muscle cells (ASM and bronchial biopsies from control donors and patients with asthma to examine the regulation of MMP-1 by ECM in ASM cells and the effect of MMP-1 on ASM contraction. Collagen-I and tenascin-C induced MMP-1 protein expression, which for tenascin-C, was greater in asthma derived ASM cells. Tenascin-C induced MMP-1 expression was dependent on ERK1/2, JNK and p38 MAPK activation and attenuated by function blocking antibodies against the β1 and β3 integrin subunits. Tenascin-C and MMP-1 were not expressed in normal airways but co-localised in the ASM bundles and reticular basement membrane of patients with asthma. Further, ECM from asthma derived ASM cells stimulated MMP-1 expression to a greater degree than ECM from normal ASM. Bradykinin induced contraction of ASM cells seeded in 3D collagen gels was reduced by the MMP inhibitor ilomastat and by siRNA knockdown of MMP-1. In summary, the induction of MMP-1 in ASM cells by tenascin-C occurs in part via integrin mediated MAPK signalling. MMP-1 and tenascin-C are co-localised in the smooth muscle bundles of patients with asthma where this interaction may contribute to enhanced airway contraction. Our findings suggest that ECM changes in airway remodelling via MMP-1 could contribute to an environment promoting greater airway narrowing in response to broncho-constrictor stimuli and worsening asthma symptoms.

  13. Effects of pinacidil on proliferation of cultured rabbit airway smooth muscle cells induced by endothelin-1

    Institute of Scientific and Technical Information of China (English)

    WANG Hong; XIE Wei-ping; QI Xu; ZHANG Xi-long

    2005-01-01

    @@ It has been found that the potassium channel dysfunction of the membrane of airway smooth muscle cells (ASMCs) is closely associated with proliferation of ASMCs.1 Preliminary research has demonstrated that pinacidil, an ATP sensitive potassium channel (KATP) opener, could play a remarkable role in the prevention and treatment of antigen induced bronchial asthma in guinea pigs.2 This study was designed to investigate further the role and molecular mechanism of the proliferation of ASMCs: a chief pathological change of the nonacute phase of bronchial asthmatic episodes.

  14. Pituitary Adenylate Cyclase-Activating Polypeptide Reverses Ammonium Metavanadate-Induced Airway Hyperresponsiveness in Rats

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    Mounira Tlili

    2015-01-01

    Full Text Available The rate of atmospheric vanadium is constantly increasing due to fossil fuel combustion. This environmental pollution favours vanadium exposure in particular to its vanadate form, causing occupational bronchial asthma and bronchitis. Based on the well admitted bronchodilator properties of the pituitary adenylate cyclase-activating polypeptide (PACAP, we investigated the ability of this neuropeptide to reverse the vanadate-induced airway hyperresponsiveness in rats. Exposure to ammonium metavanadate aerosols (5 mg/m3/h for 15 minutes induced 4 hours later an array of pathophysiological events, including increase of bronchial resistance and histological alterations, activation of proinflammatory alveolar macrophages, and increased oxidative stress status. Powerfully, PACAP inhalation (0.1 mM for 10 minutes alleviated many of these deleterious effects as demonstrated by a decrease of bronchial resistance and histological restoration. PACAP reduced the level of expression of mRNA encoding inflammatory chemokines (MIP-1α, MIP-2, and KC and cytokines (IL-1α and TNF-α in alveolar macrophages and improved the antioxidant status. PACAP reverses the vanadate-induced airway hyperresponsiveness not only through its bronchodilator activity but also by counteracting the proinflammatory and prooxidative effects of the metal. Then, the development of stable analogs of PACAP could represent a promising therapeutic alternative for the treatment of inflammatory respiratory disorders.

  15. Effects of Angelicin on Ovalbumin (OVA)-Induced Airway Inflammation in a Mouse Model of Asthma.

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    Wei, Da-Zhen; Guo, Xian-Yang; Lin, Li-Na; Lin, Meng-Xiang; Gong, Yu-Qiang; Ying, Bin-Yu; Huang, Ming-Yuan

    2016-12-01

    Angelicin, a furocoumarin found in Psoralea corylifolia L. fruit, has been reported to have anti-inflammatory activity. The purpose of this study was to determine the protective effects of angelicin on allergic asthma induced by ovalbumin (OVA) in mice. Mice were sensitized to OVA (on days 0 and 14) and challenged with OVA three times (on days 21 to 23). Angelicin (2.5, 5, 10 mg/kg) was given intraperitoneally 1 h before OVA treatment after the initial OVA sensitization. The production of IL-4, IL-5, and IL-13 in BALF and IgE in the serum were measured by ELISA. Lung histological changes were detected by using hematoxylin and eosin (H&E) stain. The results showed that angelicin significantly inhibited inflammatory cells infiltration into the lungs. Histological studies showed that angelicin significantly attenuated OVA-induced lung injury. Meanwhile, treatment of angelicin dose-dependently inhibited OVA-induced the production of IL-4, IL-5, and IL-13 in BALF and IgE in the serum. Furthermore, angelicin was found to inhibit airway hyperresponsiveness and NF-kB activation. In conclusion, our results suggested that angelicin inhibited allergic airway inflammation and hyperresponsiveness by inhibiting NF-kB activation.

  16. Morin Attenuates Ovalbumin-Induced Airway Inflammation by Modulating Oxidative Stress-Responsive MAPK Signaling

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    Yuan Ma

    2016-01-01

    Full Text Available Asthma is one of the most common inflammatory diseases characterized by airway hyperresponsiveness, inflammation, and remodeling. Morin, an active ingredient obtained from Moraceae plants, has been demonstrated to have promising anti-inflammatory activities in a range of disorders. However, its impacts on pulmonary diseases, particularly on asthma, have not been clarified. This study was designed to investigate whether morin alleviates airway inflammation in chronic asthma with an emphasis on oxidative stress modulation. In vivo, ovalbumin- (OVA- sensitized mice were administered with morin or dexamethasone before challenge. Bronchoalveolar lavage fluid (BALF and lung tissues were obtained to perform cell counts, histological analysis, and enzyme-linked immunosorbent assay. In vitro, human bronchial epithelial cells (BECs were challenged by tumor necrosis factor alpha (TNF-α. The supernatant was collected for the detection of the proinflammatory proteins, and the cells were collected for reactive oxygen species (ROS/mitogen-activated protein kinase (MAPK evaluations. Severe inflammatory responses and remodeling were observed in the airways of the OVA-sensitized mice. Treatment with morin dramatically attenuated the extensive trafficking of inflammatory cells into the BALF and inhibited their infiltration around the respiratory tracts and vessels. Morin administration also significantly suppressed goblet cell hyperplasia and collagen deposition/fibrosis and dose-dependently inhibited the OVA-induced increases in IgE, TNF-α, interleukin- (IL- 4, IL-13, matrix metalloproteinase-9, and malondialdehyde. In human BECs challenged by TNF-α, the levels of proteins such as eotaxin-1, monocyte chemoattractant protein-1, IL-8 and intercellular adhesion molecule-1, were consistently significantly decreased by morin. Western blotting and the 2′,7′-dichlorofluorescein assay revealed that the increases in intracellular ROS and MAPK phosphorylation were

  17. Induced sputum is a reproducible method to assess airway inflammation in asthma

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    Elena Bacci

    2002-01-01

    Full Text Available To evaluate the reproducibility of induced sputum analysis, and to estimate the sample size required to obtained reliable results, sputum was induced by hypertonic saline inhalation in 29 asthmatic subjects on two different days. The whole sample method was used for analysis, and inflammatory cells were counted on cytospin slides. Reproducibility, expressed by intra-class correlation coefficients, was good for macrophages (+0.80, neutrophils (+0.85, and eosinophils (+0.87, but not for lymphocytes (+0.15. Detectable differences were 5.5% for macrophages, 0.6% for lymphocytes, 5.2% for neutrophils, and 3.0% for eosinophils. We conclude that analysis of induced sputum is a reproducible method to study airway inflammation in asthma. Sample sizes greater than ours give little improvement in the detectable difference of eosinophil percentages.

  18. Effect of Moringa oleifera Lam. seed extract on ovalbumin-induced airway inflammation in guinea pigs.

    Science.gov (United States)

    Mahajan, Shailaja G; Mehta, Anita A

    2008-08-01

    To determine the therapeutic potential of herbal medicine Moringa oleifera Lam. family: Moringaceae in the control of allergic diseases, the efficacy of the ethanolic extract of the seeds of the plant (MOEE) against ovalbumin (OVA)-induced airway inflammation in guinea pigs was examined. During the experimental period, the test drugs (MOEE or dexamethasone) were administered by oral route prior to challenge with aerosolized 0.5% OVA. Bronchoconstriction tests were performed and respiratory parameters (i.e., tidal volume and respiratory rate) were measured. At the end of experiment, blood was collected from each animal to perform total and differential counts and serum was used for assay of IL-4, IL-6, and TNFalpha. Lung lavage fluid (BAL) was collected for estimation of cellular content and cytokine levels. Lung tissue histamine assays were performed using the homogenate of one lobe from each animal; a separate lobe and the trachea were subjected to histopathology to measure the degree of any airway inflammation. The results suggest that in OVA-sensitized control animals that did not receive either drug, tidal volume (V(t)) was decreased, respiration rate (f) was increased, and both the total and differential cell counts in blood and BAL fluid were increased significantly. MOEE-treatment of sensitized hosts resulted in improvement in all parameters except BAL TNFalpha and IL-4. Moreover, MOEE-treatment also showed protection against acetylcholine-induced broncho-constriction and airway inflammation which was confirmed by histological observations. The results of these studies confirm the traditional claim for the usefulness of this herb in the treatment of allergic disorders like asthma.

  19. Up-Regulation of Endothelin Receptors Induced by Cigarette Smoke — Involvement of MAPK in Vascular and Airway Hyper-Reactivity

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    Yaping Zhang

    2010-01-01

    Full Text Available Cigarette smoke exposure is well known to cause cardiovascular and airway diseases, both of which are leading causes of death and disability in the world. However, the molecular mechanisms that link cigarette smoke to cardiovascular and airway diseases are not fully understood. Vascular and airway hyper-reactivity plays an important role in the pathogenesis of cardiovascular and airway diseases. Recent studies have demonstrated that endothelin receptor up-regulation mediates vascular and airway hyper-reactivity in response to endothelin-1 (ET-1, endothelin receptor agonist in cardiovascular and airway diseases. In the vasculature and airways, the main functional consequences of up-regulated endothelin receptors by cigarette smoke exposure are enhanced contraction and proliferation of the smooth muscle cells, which subsequently result in abnormal contraction (spasm and adverse proliferation (remodeling of the vasculature and airways. The structural alteration by adverse remodeling involves changes in cell growth, cell death, cell migration, and production or degradation of the extracellular matrix. This review focuses on cigarette smoke exposure that induces activation of intracellular mitogen-activated protein kinase (MAPK and subsequently results in the up-regulation of endothelin receptors in the vasculature and airways, which mediates vascular and airway hyper-reactivity, one of the important pathogenic characteristics of cardiovascular and airway diseases. Understanding the molecular mechanisms of how cigarette smoke causes up-regulation of endothelin receptors in the vasculature and airways may provide new strategies for the treatment of cigarette smoke—associated cardiovascular and lung diseases.

  20. [Desflurane anesthesia without muscle relaxant for a patient with myasthenia gravis undergoing laparoscopic high anterior resection: a case report].

    Science.gov (United States)

    Koda, Kenichiro; Kimura, Haruka; Uzawa, Masashi; Sambe, Norie; Sugano, Takayuki; Kitamura, Takayuki; Tagami, Megumi

    2014-10-01

    Myasthenia gravis (MG) is an autoimmune disease affecting neuromuscular junction, which is characterized by fluctuating muscle weakness and abnormal fatigability. The use of muscle relaxants is major concern in anesthetic management for patients with MG. Muscle relaxant is a practical tool to assure immobilization during surgery under general anesthesia Anesthetic management without muscle relaxants for patients with MG is challenging, because it is difficult to assure immobilization. However, pharmacological effects of muscle relaxants can be prolonged in patients with MG, resulting in the increased incidence of postoperative respiratory support. We, here, describe an anesthetic management of an 82-year-old man with MG undergoing laparoscopic surgery. Anesthesia was induced with propofol and remifentanil Desflurane was administered via a face mask, and the patient was manually ventilated for 10 min, and the trachea was intubated safely without muscle relaxants. Anesthesia was maintained with desflurane and remifentanil. We did not administer muscle relaxants to the patient during surgery. Throughout laparoscopic procedures, no movements of the patient were observed, and there were no problems concerning the laparoscopic view of the operation filed. The surgery was uneventful. The patient emerged from anesthesia smoothly, and was extubated safely. The postoperative course of the patient was also uneventful.

  1. Prostaglandin E2 induces expression of MAPK phosphatase 1 (MKP-1) in airway smooth muscle cells.

    Science.gov (United States)

    Rumzhum, Nowshin N; Ammit, Alaina J

    2016-07-05

    Prostaglandin E2 (PGE2) is a prostanoid with diverse actions in health and disease. In chronic respiratory diseases driven by inflammation, PGE2 has both positive and negative effects. An enhanced understanding of the receptor-mediated cellular signalling pathways induced by PGE2 may help us separate the beneficial properties from unwanted actions of this important prostaglandin. PGE2 is known to exert anti-inflammatory and bronchoprotective actions in human airways. To date however, whether PGE2 increases production of the anti-inflammatory protein MAPK phosphatase 1 (MKP-1) was unknown. We address this herein and use primary cultures of human airway smooth muscle (ASM) cells to show that PGE2 increases MKP-1 mRNA and protein upregulation in a concentration-dependent manner. We explore the signalling pathways responsible and show that PGE2-induces CREB phosphorylation, not p38 MAPK activation, in ASM cells. Moreover, we utilize selective antagonists of EP2 (PF-04418948) and EP4 receptors (GW 627368X) to begin to identify EP-mediated functional outcomes in ASM cells in vitro. Taken together with earlier studies, our data suggest that PGE2 increases production of the anti-inflammatory protein MKP-1 via cAMP/CREB-mediated cellular signalling in ASM cells and demonstrates that EP2 may, in part, be involved. Copyright © 2016 Elsevier B.V. All rights reserved.

  2. ExoU-induced procoagulant activity in Pseudomonas aeruginosa-infected airway cells.

    Science.gov (United States)

    Plotkowski, M C; Feliciano, L F P; Machado, G B S; Cunha, L G; Freitas, C; Saliba, A M; de Assis, M C

    2008-12-01

    The present study addressed the question whether ExoU, a Pseudomonas aeruginosa toxin with phospholipase A2 (PLA2) activity, may induce airway epithelial cells to overexpress tissue factor (TF) and exhibit a procoagulant phenotype. Cells from the human bronchial epithelial BEAS-2B line were infected with an ExoU-producing P. aeruginosa strain, pre-treated or not with the cytosolic PLA2 inhibitor methylarachidonyl fluorophosphate (MAFP), or with two ExoU-deficient mutants. Control noninfected and infected cells were assessed for the expression of: 1) TF mRNA by RT-PCR; 2) cell-associated TF by enzyme immunoassay and flow cytometry; 3) procoagulant activity by a colorimetric assay; and 4) microparticle-associated TF by flow cytometry. An enzyme immunoassay was also used to assess cell-associated TF in lung extracts from mice infected intratracheally with ExoU-producing and -deficient bacteria. Cells infected with the wild-type bacteria had higher levels of TF mRNA, cell-associated TF expression, procoagulant activity and released microparticle-associated TF than cells infected with the mutants. Bacterial treatment with MAFP significantly reduced the expression of TF by infected cells. Lung samples from mice infected with the wild-type bacteria exhibited higher levels of cell-associated TF and procoagulant activity. The present results demonstrate that ExoU may contribute to the pathogenesis of lung injury by inducing a tissue factor-dependent procoagulant activity in airway epithelial cells.

  3. Interaction of ozone exposure with airway hyperresponsiveness and inflammation induced by trimellitic anhydride in sensitized guinea pigs

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    Sun, Jian; Chung, K.Fan [National Heart & Lung Institute, London (United Kingdom)

    1997-09-01

    The effect of prior ozone (O{sub 3}) exposure on airway hyperresponsiveness and inflammation induced by trimellitic anhydride (TMA) has been investigated in TMA-sensitized guinea pigs. Airway responsiveness was measured as the concentration of acetylcholine needed to increase baseline lung resistance (RL) by 300% (PC300). Ozone (3 ppm, for 3 h) caused an increase in-log PC300 at 1 h after exposure, with return of -log PC300 to control levels at 8 h. Ozone also increased baseline RL at 8 h. TMA challenge increase -log PC300 in TMA-sensitized guinea pigs at 8 h after challenge from 3.85 {+-} 0.09 to 4.11 {+-} 0.09. Ozone exposure prior to TMA challenge prevented the induction of airway hyperresponsiveness with a mean -log PC300 of 3.51 {+-} 0.20, which was not different from that of control TMA-Sensitized group. Baseline RL was significantly higher in ozone-pretreated animals after TMA challenge when compared to those of either control or challenged with TMA alone. Ozone had no effect on TMA challenge-induced BAL eosinophilia and neutrophilia. We conclude that a single exposure to ozone inhibits the increase in airway responsiveness, but increases the bronchoconstrictor response induced by TMA in TMA-Sensitized guinea pigs; however, the inflammatory airway response to TMA is unchanged by preexposure to ozone. 29 refs., 2 figs., 1 tab.

  4. Effects of nebulized ketamine on allergen-induced airway hyperresponsiveness and inflammation in actively sensitized Brown-Norway rats

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    Qian Yan

    2007-05-01

    Full Text Available Abstract Since airway hyperresponsiveness (AHR and allergic inflammatory changes are regarded as the primary manifestations of asthma, the main goals of asthma treatment are to decrease inflammation and maximize bronchodilation. These goals can be achieved with aerosol therapy. Intravenous administration of the anesthetic, ketamine, has been shown to trigger bronchial smooth muscle relaxation. Furthermore, increasing evidence suggests that the anti-inflammatory properties of ketamine may protect against lung injury. However, ketamine inhalation might yield the same or better results at higher airway and lower ketamine plasma concentrations for the treatment of asthma. Here, we studied the effect of ketamine inhalation on bronchial hyperresponsiveness and airway inflammation in a Brown-Norway rat model of ovalbumin(OVA-induced allergic asthma. Animals were actively sensitized by subcutaneous injection of OVA and challenged by repeated intermittent (thrice weekly exposure to aerosolized OVA for two weeks. Before challenge, the sensitizened rats received inhalation of aerosol of phosphate-buffered saline (PBS or aerosol of ketamine or injection of ketamine respectivity. Airway reactivity to acetylcholine (Ach was measured in vivo, and various inflammatory markers, including Th2 cytokines in bronchoalveolar lavage fluid (BALF, as well as induciable nitric oxide synthase (iNOS and nitric oxide (NO in lungs were examined. Our results revealed that delivery of aerosolized ketamine using an ultrasonic nebulizer markedly suppressed allergen-mediated airway hyperreactivity, airway inflammation and airway inflammatory cell infiltration into the BALF, and significantly decreased the levels of interleukin-4 (IL-4 in the BALF and expression of iNOS and the concentration of NO in the inflamed airways from OVA-treated rats. These findings collectively indicate that nebulized ketamine attenuated many of the central components of inflammatory changes and AHR in

  5. Effects of combination therapy with montelukast and carbocysteine in allergen-induced airway hyperresponsiveness and airway inflammation.

    Science.gov (United States)

    Takeda, K; Shiraishi, Y; Matsubara, S; Miyahara, N; Matsuda, H; Okamoto, M; Joetham, A; Gelfand, E W

    2010-07-01

    Montelukast and S-carbocysteine have been used in asthmatic patients as an anti-inflammatory or mucolytic agent respectively. S-carbocysteine also exhibits anti-inflammatory properties. Ovalbumin (OVA) sensitized BALB/c mice were challenged with OVA for 3 days followed by single OVA re-challenge (secondary challenge) 2 weeks later. Forty-eight hours after secondary challenge, mice were assessed for airway hyperresponsiveness (AHR) and cell composition in bronchoalveolar lavage (BAL) fluid. Suboptimal doses of 10 mg.kg(-1) of S-carbocysteine by intraperitoneal injection (ip), 20 mg.kg(-1) of montelukast by gavage, the combination of S-carbocysteine and montelukast or 3 mg.kg(-1) of dexamethasone as a control were administered from 1 day before the secondary challenge to the last experimental day. Isolated lung cells were cultured with OVA and montelukast to determine the effects on cytokine production. Treatment with S-carbocysteine or montelukast reduced both AHR and the numbers of eosinophils in BAL fluid. Neutralizing IFN-gamma abolished the effects of S-carbocysteine on these airway responses. Combination of the two drugs showed further decreases in both AHR and eosinophils in the BAL fluid. Goblet cell metaplasia and Th2-type cytokines, interleukin (IL)-4, IL-5 and IL-13, in BAL fluid were decreased with montelukast treatment. Conversely, S-carbocysteine increased Th1-type cytokines, IFN-gamma and IL-12 in BAL fluid. The combination of two agents, montelukast and S-carbocysteine, demonstrated additive effects on AHR and airway inflammation in a secondary allergen model most likely through independent mechanisms of action.

  6. Persistence of enhanced aerosol deposition in the lung after recovery from carbachol-induced airway obstruction.

    Science.gov (United States)

    Kim, C S; Garcia, L; Eldridge, M A; Wanner, A

    1990-12-01

    Time course recovery from induced airway obstruction by carbachol infusion (CI; 0.2 microgram.kg-1.min-1 for 40 min), carbachol aerosol (CA; 10 breaths of 2% solution), and histamine aerosol (HA; 25-50 breaths of 5% solution) challenge was investigated in conscious sheep (n = 6 each). Total lung aerosol deposition and airway caliber as assessed by pulmonary airflow resistance (RL) were measured every 20-30 min up to 4 h after the challenges. Aerosol deposition was measured by monitoring aerosol concentration continuously with a laser aerosol photometer while the sheep rebreathed 1.0-micron-diam inert oil droplets delivered by a 0.25-liter bag-in-box system driven by a respiratory pump at a breathing frequency of 30 breaths/min. Total accumulated deposition at the fifth breath (AD5) as percentage of the initial aerosol concentration was determined and used as an aerosol deposition index. Percent changes in AD5 from baseline were compared with corresponding changes in RL. Both RL and AD5 increased after Cl, CA, and HA: 192-477% for RL and 23-44% for AD5 (P less than 0.05). Mean RL return to baseline values 1 h after CI and HA and 2 h after CA. Mean AD5 returned to baseline at 1 h post-HA. In contrast, mean AD5 remained elevated for 2-4 h after CI and CA (P less than 0.05), and the increased AD5 could not be reversed by a bronchodilator aerosol. The persistence of enhanced aerosol deposition long after the return of RL to baseline suggests that complete recovery of airway conditions after CI and CA takes much longer than predicted by RL.(ABSTRACT TRUNCATED AT 250 WORDS)

  7. Trimellitic anhydride (TMA) dust induces airway obstruction and eosinophilia in non-sensitized guinea pigs.

    Science.gov (United States)

    Larsen, Christen P; Regal, Jean F

    2002-09-02

    Trimellitic anhydride (TMA) causes asthma after a latency period of sensitization. In non-sensitized humans and animals, limited studies indicate that TMA exposure may also cause symptoms of asthma without a latency period. Our previous studies (J. Pharmacol. Exp. Ther. 296 (2001) 284) in a guinea pig model of TMA-induced asthma demonstrated that sensitization and the complement system were required for eosinophilia. TMA conjugated to guinea pig serum albumin (TMA-GPSA) was used to elicit the response. Since occupational exposure to TMA occurs by inhalation of dust, the present studies determined if exposure to TMA dust in a non-sensitized guinea pig elicited airway obstruction and inflammation, and whether a significantly greater response occurred after a latency period of sensitization. Guinea pigs were intradermally injected with either corn oil (non-sensitized animals) or 30% TMA (sensitized animals). Three weeks later they were challenged by intratracheal insufflation with 1 mg TMA dust or lactose dust (control) using a dry powder delivery device. Pulmonary resistance, dynamic lung compliance, mean arterial blood pressure and heart rate were monitored for 10 min. In non-sensitized guinea pigs, significant increases in pulmonary resistance and decreases in dynamic lung compliance and blood pressure occurred after TMA challenge. In sensitized animals, the same dose of TMA caused significantly greater effects compared to non-sensitized animals. In a separate experiment, cellular infiltration into the lung was determined 24 h after challenge with TMA dust or lactose dust. In both non-sensitized and sensitized animals, eosinophils in the lung tissue were increased after TMA dust challenge compared to controls. Thus, these studies suggest that the response in non-sensitized animals differs depending on whether TMA dust or TMA-GPSA is used to elicit the response. TMA dust elicits significant airway obstruction and eosinophilia in a non-sensitized animal, with even

  8. Cigarette smoke modulates expression of human rhinovirus-induced airway epithelial host defense genes.

    Directory of Open Access Journals (Sweden)

    David Proud

    Full Text Available Human rhinovirus (HRV infections trigger acute exacerbations of chronic obstructive pulmonary disease (COPD and asthma. The human airway epithelial cell is the primary site of HRV infection and responds to infection with altered expression of multiple genes, the products of which could regulate the outcome to infection. Cigarette smoking aggravates asthma symptoms, and is also the predominant risk factor for the development and progression of COPD. We, therefore, examined whether cigarette smoke extract (CSE modulates viral responses by altering HRV-induced epithelial gene expression. Primary cultures of human bronchial epithelial cells were exposed to medium alone, CSE alone, purified HRV-16 alone or to HRV-16+ CSE. After 24 h, supernatants were collected and total cellular RNA was isolated. Gene array analysis was performed to examine mRNA expression. Additional experiments, using real-time RT-PCR, ELISA and/or western blotting, validated altered expression of selected gene products. CSE and HRV-16 each induced groups of genes that were largely independent of each other. When compared to gene expression in response to CSE alone, cells treated with HRV+CSE showed no obvious differences in CSE-induced gene expression. By contrast, compared to gene induction in response to HRV-16 alone, cells exposed to HRV+CSE showed marked suppression of expression of a number of HRV-induced genes associated with various functions, including antiviral defenses, inflammation, viral signaling and airway remodeling. These changes were not associated with altered expression of type I or type III interferons. Thus, CSE alters epithelial responses to HRV infection in a manner that may negatively impact antiviral and host defense outcomes.

  9. Protein kinase C epsilon is important in modulating organic-dust-induced airway inflammation.

    Science.gov (United States)

    Poole, Jill A; Romberger, Debra J; Bauer, Chris; Gleason, Angela M; Sisson, Joseph H; Oldenburg, Peter J; West, William W; Wyatt, Todd A

    2012-10-01

    Organic dust samples from swine confinement facilities elicit pro-inflammatory cytokine/chemokine release from bronchial epithelial cells and monocytes, dependent, in part, upon dust-induced activation of the protein kinase C (PKC) isoform, PKCε. PKCε is also rapidly activated in murine tracheal epithelial cells following in vivo organic dust challenges, yet the functional role of PKCε in modulating dust-induced airway inflammatory outcomes is not defined. Utilizing an established intranasal inhalation animal model, experiments investigated the biologic and physiologic responses following organic dust extract (ODE) treatments in wild-type (WT) and PKCε knock-out (KO) mice. We found that neutrophil influx increased more than twofold in PKCε KO mice following both a one-time challenge and 3 weeks of daily challenges with ODE as compared with WT mice. Lung pathology revealed increased bronchiolar and alveolar inflammation, lymphoid aggregates, and T cell influx in ODE-treated PKCε KO mice. Airway hyperresponsiveness to methacholine increased in PKCε KO + ODE to a greater magnitude than WT + ODE animals. There were no significant differences in cytokine/chemokine release elicited by ODE treatment between groups. However, ODE-induced nitric oxide (NO) production differed in that ODE exposure increased nitrate levels in WT mice but not in PKCε KO mice. Moreover, ODE failed to upregulate NO from ex vivo stimulated PKCε KO lung macrophages. Collectively, these studies demonstrate that PKCε-deficient mice were hypersensitive to organic dust exposure and suggest that PKCε is important in the normative lung inflammatory response to ODE. Dampening of ODE-induced NO may contribute to these enhanced inflammatory findings.

  10. Inhibitory effects of l-theanine on airway inflammation in ovalbumin-induced allergic asthma.

    Science.gov (United States)

    Hwang, Yong Pil; Jin, Sun Woo; Choi, Jae Ho; Choi, Chul Yung; Kim, Hyung Gyun; Kim, Se Jong; Kim, Yongan; Lee, Kyung Jin; Chung, Young Chul; Jeong, Hye Gwang

    2017-01-01

    l-theanine, a water-soluble amino acid isolated from green tea (Camellia sinensis), has anti-inflammatory activity, antioxidative properties, and hepatoprotective effects. However, the anti-allergic effect of l-theanine and its underlying molecular mechanisms have not been elucidated. In this study, we investigated the protective effects of l-theanine on asthmatic responses, particularly airway inflammation and oxidative stress modulation in an ovalbumin (OVA)-induced murine model of asthma. Treatment with l-theanine dramatically attenuated the extensive trafficking of inflammatory cells into bronchoalveolar lavage fluid (BALF). Histological studies revealed that l-theanine significantly inhibited OVA-induced mucus production and inflammatory cell infiltration in the respiratory tract and blood vessels. l-theanine administration also significantly decreased the production of IgE, monocyte chemoattractant protein-1 (MCP-1), interleukin (IL)-4, IL-5, IL-13, tumor necrosis factor-alpha (TNF-α), and interferon-gamma in BALF. The lung weight decreased with l-theanine administration. l-theanine also markedly attenuated the OVA-induced generation of reactive oxygen species and the activation of nuclear factor kappa B (NF-κB) and matrix metalloprotease-9 in BALF. Moreover, l-theanine reduced the TNF-α-induced NF-κB activation in A549 cells. Together, these results suggest that l-theanine alleviates airway inflammation in asthma, which likely occurs via the oxidative stress-responsive NF-κB pathway, highlighting its potential as a useful therapeutic agent for asthma management.

  11. Specific allergen immunotherapy attenuates allergic airway inflammation in a rat model of Alstonia scholaris pollen induced airway allergy.

    Science.gov (United States)

    Datta, Ankur; Moitra, Saibal; Hazra, Iman; Mondal, Somnath; Das, Prasanta Kumar; Singh, Manoj Kumar; Chaudhuri, Suhnrita; Bhattacharya, Debanjan; Tripathi, Santanu Kumar; Chaudhuri, Swapna

    2016-01-01

    Pollen grains are well established to be an important cause of respiratory allergy. Current pharmacologic therapies for allergic asthma do not cure the disease. Allergen specific immunotherapy is the only treatment method which re-directs the immune system away from allergic response leading to a long lasting effect. The mechanism by which immunotherapy achieves this goal is an area of active research world-wide. The present experimental study was designed to develop an experimental model of allergic lung inflammation based on a relevant human allergen, Alstonia scholaris pollen, and to establish the immunological and cellular features of specific allergen immunotherapy using this same pollen extract. Our results revealed that Alstonia scholaris pollen sensitization and challenge causes eosinophilic airway inflammation with mucin hypersecretion. This is associated with increased total IgE, increased expression of FcɛRI on lung mast cells and increased levels of IL-4, IL-5 & IL-13 as confirmed by ELISA, in-situ immunofluorescence and FACS assay. Allergen specific immunotherapy reduced airway inflammation and also decreased total IgE level, FcɛRI expression, IL-4, IL-5 & IL-13 levels. It was further noted that the reduction of these levels was more by intra-nasal route than by intra-peritoneal route. Thus we present a novel animal model of Alstonia scholaris pollen allergic disease and specific allergen immunotherapy which will pave the way towards the development of better treatment modalities.

  12. Chlamydia pneumoniae infection induced allergic airway sensitization is controlled by regulatory T-cells and plasmacytoid dendritic cells.

    Directory of Open Access Journals (Sweden)

    Timothy R Crother

    Full Text Available Chlamydia pneumoniae (CP is associated with induction and exacerbation of asthma. CP infection can induce allergic airway sensitization in mice in a dose- and time-dependent manner. Allergen exposure 5 days after a low dose (mild-moderate, but not a high dose (severe CP infection induces antigen sensitization in mice. Innate immune signals play a critical role in controlling CP infection induced allergic airway sensitization, however these mechanisms have not been fully elucidated. Wild-type, TLR2-/-, and TLR4-/- mice were infected intranasally (i.n. with a low dose of CP, followed by i.n. exposure to human serum albumin (HSA and challenged with HSA 2 weeks later. Airway inflammation, immunoglobulins, eosinophils, and goblet cells were measured. Low dose CP infection induced allergic sensitization in TLR2-/- mice, but not in TLR4-/- mice, due to differential Treg responses in these genotypes. TLR2-/- mice had reduced numbers of Tregs in the lung during CP infection while TLR4-/- mice had increased numbers. High dose CP infection resulted in an increase in Tregs and pDCs in lungs, which prevented antigen sensitization in WT mice. Depletion of Tregs or pDCs resulted in allergic airway sensitization. We conclude that Tregs and pDCs are critical determinants regulating CP infection-induced allergic sensitization. Furthermore, TLR2 and TLR4 signaling during CP infection may play a regulatory role through the modulation of Tregs.

  13. Chlamydia pneumoniae infection induced allergic airway sensitization is controlled by regulatory T-cells and plasmacytoid dendritic cells.

    Science.gov (United States)

    Crother, Timothy R; Schröder, Nicolas W J; Karlin, Justin; Chen, Shuang; Shimada, Kenichi; Slepenkin, Anatoly; Alsabeh, Randa; Peterson, Ellena; Arditi, Moshe

    2011-01-01

    Chlamydia pneumoniae (CP) is associated with induction and exacerbation of asthma. CP infection can induce allergic airway sensitization in mice in a dose- and time-dependent manner. Allergen exposure 5 days after a low dose (mild-moderate), but not a high dose (severe) CP infection induces antigen sensitization in mice. Innate immune signals play a critical role in controlling CP infection induced allergic airway sensitization, however these mechanisms have not been fully elucidated. Wild-type, TLR2-/-, and TLR4-/- mice were infected intranasally (i.n.) with a low dose of CP, followed by i.n. exposure to human serum albumin (HSA) and challenged with HSA 2 weeks later. Airway inflammation, immunoglobulins, eosinophils, and goblet cells were measured. Low dose CP infection induced allergic sensitization in TLR2-/- mice, but not in TLR4-/- mice, due to differential Treg responses in these genotypes. TLR2-/- mice had reduced numbers of Tregs in the lung during CP infection while TLR4-/- mice had increased numbers. High dose CP infection resulted in an increase in Tregs and pDCs in lungs, which prevented antigen sensitization in WT mice. Depletion of Tregs or pDCs resulted in allergic airway sensitization. We conclude that Tregs and pDCs are critical determinants regulating CP infection-induced allergic sensitization. Furthermore, TLR2 and TLR4 signaling during CP infection may play a regulatory role through the modulation of Tregs.

  14. Mouse models of rhinovirus-induced disease and exacerbation of allergic airway inflammation.

    Science.gov (United States)

    Bartlett, Nathan W; Walton, Ross P; Edwards, Michael R; Aniscenko, Juliya; Caramori, Gaetano; Zhu, Jie; Glanville, Nicholas; Choy, Katherine J; Jourdan, Patrick; Burnet, Jerome; Tuthill, Tobias J; Pedrick, Michael S; Hurle, Michael J; Plumpton, Chris; Sharp, Nigel A; Bussell, James N; Swallow, Dallas M; Schwarze, Jurgen; Guy, Bruno; Almond, Jeffrey W; Jeffery, Peter K; Lloyd, Clare M; Papi, Alberto; Killington, Richard A; Rowlands, David J; Blair, Edward D; Clarke, Neil J; Johnston, Sebastian L

    2008-02-01

    Rhinoviruses cause serious morbidity and mortality as the major etiological agents of asthma exacerbations and the common cold. A major obstacle to understanding disease pathogenesis and to the development of effective therapies has been the lack of a small-animal model for rhinovirus infection. Of the 100 known rhinovirus serotypes, 90% (the major group) use human intercellular adhesion molecule-1 (ICAM-1) as their cellular receptor and do not bind mouse ICAM-1; the remaining 10% (the minor group) use a member of the low-density lipoprotein receptor family and can bind the mouse counterpart. Here we describe three novel mouse models of rhinovirus infection: minor-group rhinovirus infection of BALB/c mice, major-group rhinovirus infection of transgenic BALB/c mice expressing a mouse-human ICAM-1 chimera and rhinovirus-induced exacerbation of allergic airway inflammation. These models have features similar to those observed in rhinovirus infection in humans, including augmentation of allergic airway inflammation, and will be useful in the development of future therapies for colds and asthma exacerbations.

  15. The role of toll-like receptor 4 in airway inflammation induced by diesel exhaust particles

    Energy Technology Data Exchange (ETDEWEB)

    Inoue, Ken-ichiro; Yanagisawa, Rie; Hirano, Seishiro [National Institute for Environmental Studies, Environmental Health Sciences Division, Tsukuba (Japan); Takano, Hirohisa; Yoshikawa, Toshikazu [Kyoto Prefectural University of Medicine, Inflammation and Immunology, Graduate School of Medical Science, Kyoto (Japan); Ichinose, Takamichi [Oita University of Nursing and Health Science, Department of Health Science, Oita (Japan); Shimada, Akinori [Tottori University, Department of Veterinary Pathology, Faculty of Agriculture, Tottori (Japan)

    2006-05-15

    Although several studies have demonstrated that airway exposure to diesel exhaust particles (DEP) induces lung inflammation, the signaling pathways involved in the pathogenesis remain unclear. Toll-like receptors (TLRs) are generally accepted to be pathogen recognition receptors in mammalians. In the present study, we investigated the role of TLR-4 in DEP-induced lung inflammation and cytokine expression in the lung in TLR-4 point mutant (C3H/HeJ) mice and corresponding control (C3H/HeN) mice. Both the types of mice were randomized into four experimental groups that received vehicle or DEP (12 mg/kg body weight) by intratracheal instillation (n=8-10 in each group). Cellular profile of bronchoalveolar lavage (BAL) fluid, expressions of cytokines and chemokines in the lung, and circulatory fibrinogen levels were evaluated 24 h after the instillation.DEP challenge revealed a significant increase in the numbers of total cells and neutrophils in the BAL fluid as compared to vehicle challenge, however, the numbers were less in C3H/HeJ mice than in C3H/HeN mice. DEP exposure significantly induced the lung expression of interleukin (IL)-1{beta}, keratinocyte chemoattractant (KC), and macrophage inflammatory protein (MIP)-1{alpha} when compared to vehicle challenge in both genotypes of mice. In the presence of DEP, the level of MIP-1{alpha} was significantly lower in C3H/HeJ mice than in C3H/HeN mice, however, the levels of IL-1{beta}, KC, and fibrinogen showed opposite findings. These results suggest that TLR-4 is one of recognition receptors against DEP in the airways. (orig.)

  16. Ambient urban Baltimore particulate-induced airway hyperresponsiveness and inflammation in mice

    Energy Technology Data Exchange (ETDEWEB)

    Walters, D.M.; Breysse, P.N.; Wills-Karp, M. [Childrens Hospital, Cincinnati, OH (United States). Medical Centre, Division of Immunobiology

    2001-10-15

    Airborne particulate matter (PM) is hypothesized to play a role in increases in asthma prevalence, although a causal relationship has yet to be established. To investigate the effects of real-world PM exposure on airway reactivity (AHR) and bronchoalveolar lavage (BAL) cellularity, mice were exposed to a single dose (0.5 mg/ mouse) of ambient PM, coal fly ash, or diesel PM. It was found that ambient PM exposure induced increases in AHR and BAL cellularity, whereas diesel PM induced significant increases in BAL cellularity, but not AHR. On the other hand, coal fly ash exposure did not elicit significant changes in either of these parameters. Ambient PM-induced temporal changes in AHR, BAL cells, and lung cytakine levels over a 2-wk period were then examined. Ambient PM-induced AHR was sustained over 7 d. The increase in AHR was preceded by dramatic increases in BAL eosinophils, whereas a decline in AHR was associated with increases in macrophages. It is concluded that ambient PM can induce asthmalike parameters in mice, suggesting that PM exposure may be an important factor in increases in asthma prevalence.

  17. Der p, IL-4, and TGF-beta cooperatively induce EGFR-dependent TARC expression in airway epithelium

    NARCIS (Netherlands)

    Heijink, Irene; Kies, P. Marcel; van Oosterhout, Antoon J. M.; Postma, Dirkje S.; Kauffman, Henk F.; Vellenga, Edo

    Thymus and Activation-Regulated Chemokine (TARC) may be critical in Th2 cell recruitment in allergic inflammation; however, the mechanisms of allergen-induced TARC release are unclear. Since airway epithelium is the first line of defense to inhaled allergens, we questioned whether house dust mite

  18. beta-Catenin signaling is required for TGF-beta(1)-induced extracellular matrix production by airway smooth muscle cells

    NARCIS (Netherlands)

    Baarsma, Hoeke A.; Menzen, Mark H.; Halayko, Andrew J.; Meurs, Herman; Kerstjens, Huib A. M.; Gosens, Reinoud

    2011-01-01

    Baarsma HA, Menzen MH, Halayko AJ, Meurs H, Kerstjens HA, Gosens R. beta-Catenin signaling is required for TGF-beta(1)-induced extracellular matrix production by airway smooth muscle cells. Am J Physiol Lung Cell Mol Physiol 301: L956-L965, 2011. First published September 9, 2011; doi: 10.1152/ajplu

  19. Schistosoma mansoni Tegument (Smteg Induces IL-10 and Modulates Experimental Airway Inflammation.

    Directory of Open Access Journals (Sweden)

    Fábio Vitarelli Marinho

    Full Text Available Previous studies have demonstrated that S. mansoni infection and inoculation of the parasite eggs and antigens are able to modulate airways inflammation induced by OVA in mice. This modulation was associated to an enhanced production of interleukin-10 and to an increased number of regulatory T cells. The S. mansoni schistosomulum is the first stage to come into contact with the host immune system and its tegument represents the host-parasite interface. The schistosomula tegument (Smteg has never been studied in the context of modulation of inflammatory disorders, although immune evasion mechanisms take place in this phase of infection to guarantee the persistence of the parasite in the host.The aim of this study was to evaluate the Smteg ability to modulate inflammation in an experimental airway inflammation model induced by OVA and to characterize the immune factors involved in this modulation. To achieve the objective, BALB/c mice were sensitized with ovalbumin (OVA and then challenged with OVA aerosol after Smteg intraperitoneal inoculation. Protein extravasation and inflammatory cells were assessed in bronchoalveolar lavage and IgE levels were measured in serum. Additionally, lungs were excised for histopathological analyses, cytokine measurement and characterization of the cell populations. Inoculation with Smteg led to a reduction in the protein levels in bronchoalveolar lavage (BAL and eosinophils in both BAL and lung tissue. In the lung tissue there was a reduction in inflammatory cells and collagen deposition as well as in IL-5, IL-13, IL-25 and CCL11 levels. Additionally, a decrease in specific anti-OVA IgE levels was observed. The reduction observed in these inflammatory parameters was associated with increased levels of IL-10 in lung tissues. Furthermore, Smteg/asthma mice showed high percentage of CD11b+F4/80+IL-10+ and CD11c+CD11b+IL-10+ cells in lungs.Taken together, these findings demonstrate that S. mansoni schistosomula

  20. Schistosoma mansoni Tegument (Smteg) Induces IL-10 and Modulates Experimental Airway Inflammation

    Science.gov (United States)

    2016-01-01

    Background Previous studies have demonstrated that S. mansoni infection and inoculation of the parasite eggs and antigens are able to modulate airways inflammation induced by OVA in mice. This modulation was associated to an enhanced production of interleukin-10 and to an increased number of regulatory T cells. The S. mansoni schistosomulum is the first stage to come into contact with the host immune system and its tegument represents the host-parasite interface. The schistosomula tegument (Smteg) has never been studied in the context of modulation of inflammatory disorders, although immune evasion mechanisms take place in this phase of infection to guarantee the persistence of the parasite in the host. Methodology and Principal Findings The aim of this study was to evaluate the Smteg ability to modulate inflammation in an experimental airway inflammation model induced by OVA and to characterize the immune factors involved in this modulation. To achieve the objective, BALB/c mice were sensitized with ovalbumin (OVA) and then challenged with OVA aerosol after Smteg intraperitoneal inoculation. Protein extravasation and inflammatory cells were assessed in bronchoalveolar lavage and IgE levels were measured in serum. Additionally, lungs were excised for histopathological analyses, cytokine measurement and characterization of the cell populations. Inoculation with Smteg led to a reduction in the protein levels in bronchoalveolar lavage (BAL) and eosinophils in both BAL and lung tissue. In the lung tissue there was a reduction in inflammatory cells and collagen deposition as well as in IL-5, IL-13, IL-25 and CCL11 levels. Additionally, a decrease in specific anti-OVA IgE levels was observed. The reduction observed in these inflammatory parameters was associated with increased levels of IL-10 in lung tissues. Furthermore, Smteg/asthma mice showed high percentage of CD11b+F4/80+IL-10+ and CD11c+CD11b+IL-10+ cells in lungs. Conclusion Taken together, these findings

  1. Role of neutrophilic inflammation in ozone-induced epithelial alterations in the nasal airways of rats

    Science.gov (United States)

    Cho, Hye Youn

    Ozone is a principal oxidant air pollutant in photochemical smog. Epithelial cells lining the centriacinar region of lung and the proximal aspects of nasal passage are primary target sites for ozone-induced injury in laboratory animals. Acute exposure of rats to high ambient concentrations of ozone (e.g., 0.5 ppm) results in neutrophilic inflammation, epithelial hyperplasia and mucous cell metaplasia (MCM) in the nasal transitional epithelium (NTE) lining the proximal nasal airways. The principal purpose of the present study was to investigate the role of pre-metaplastic cellular responses, especially neutrophilic inflammation, in the pathogenesis of ozone-induced MCM in rat NTE. For this purpose, three specific hypotheses-based whole-animal inhalation studies were conducted. Male F344/N rats were exposed in whole-body inhalation chambers to 0 (filtered air) or 0.5 ppm ozone for 1-3 days (8 h/day). Histochemical, immunochemical, molecular and morphometric techniques were used to investigate the ozone-induced cellular and molecular events in the NTE. Two in vitro studies were also conducted to examine the effects of ozone-inducible cytokines (i.e., tumor necrosis factor-alpha; TNF- a, and interleukin-6; IL-6) on mucin gene (rMuc-5AC) expression. Ozone induced a rapid increase of rMuc-5AC mRNA in nasal tissues within hours after the start of exposure. It preceded the appearance of MCM, and persisted with MCM. Ozone-induced neutrophilic inflammation accompanied the mucin gene upregulation, but was resolved when MCM first appeared in the NTE. Antibody-mediated depletion of circulating neutrophils attenuated ozone-induced MCM, although it did not affect the ozone-induced epithelial hyperplasia and mucin mRNA upregulation. In another study, it was found that preexisting neutrophilic rhinitis induced by endotoxin augmented the ozone-induced MCM. However, pre-existing rhinitis did not alter the severity of ozone-induced epithelial hyperplasia and mucin gene upregulation

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

    Science.gov (United States)

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

    2015-01-01

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

  3. Real-time imaging of ATP release induced by mechanical stretch in human airway smooth muscle cells.

    Science.gov (United States)

    Takahara, Norihiro; Ito, Satoru; Furuya, Kishio; Naruse, Keiji; Aso, Hiromichi; Kondo, Masashi; Sokabe, Masahiro; Hasegawa, Yoshinori

    2014-12-01

    Airway smooth muscle (ASM) cells within the airway walls are continually exposed to mechanical stimuli, and exhibit various functions in response to these mechanical stresses. ATP acts as an extracellular mediator in the airway. Moreover, extracellular ATP is considered to play an important role in the pathophysiology of asthma and chronic obstructive pulmonary disease. However, it is not known whether ASM cells are cellular sources of ATP secretion in the airway. We therefore investigated whether mechanical stretch induces ATP release from ASM cells. Mechanical stretch was applied to primary human ASM cells cultured on a silicone chamber coated with type I collagen using a stretching apparatus. Concentrations of ATP in cell culture supernatants measured by luciferin-luciferase bioluminescence were significantly elevated by cyclic stretch (12 and 20% strain). We further visualized the stretch-induced ATP release from the cells in real time using a luminescence imaging system, while acquiring differential interference contrast cell images with infrared optics. Immediately after a single uniaxial stretch for 1 second, strong ATP signals were produced by a certain population of cells and spread to surrounding spaces. The cyclic stretch-induced ATP release was significantly reduced by inhibitors of Ca(2+)-dependent vesicular exocytosis, 1,2-bis(o-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid tetraacetoxymethyl ester, monensin, N-ethylmaleimide, and bafilomycin. In contrast, the stretch-induced ATP release was not inhibited by a hemichannel blocker, carbenoxolone, or blockade of transient receptor potential vanilloid 4 by short interfering RNA transfection or ruthenium red. These findings reveal a novel property of ASM cells: mechanically induced ATP release may be a cellular source of ATP in the airway.

  4. Mast cells contribute to double-stranded RNA-induced augmentation of airway eosinophilia in a murine model of asthma.

    Science.gov (United States)

    Kan-o, Keiko; Matsunaga, Yuko; Fukuyama, Satoru; Moriwaki, Atsushi; Hirai-Kitajima, Hiroko; Yokomizo, Takehiko; Aritake, Kosuke; Urade, Yoshihiro; Nakanishi, Yoichi; Inoue, Hiromasa; Matsumoto, Koichiro

    2013-03-04

    Clinical studies showed the contribution of viral infection to the development of asthma. Although mast cells have multiple roles in the pathogenesis of allergic asthma, their role of in the virus-associated pathogenesis of asthma remains unknown. Most respiratory viruses generate double-stranded (ds) RNA during their replication. dsRNA provokes innate immune responses. We recently showed that an administration of polyinocinic polycytidilic acid (poly IC), a mimetic of viral dsRNA, during allergen sensitization augments airway eosinophilia and hyperresponsiveness in mice via enhanced production of IL-13. The effect of poly IC on allergen-induced airway eosinophilia was investigated for mast cell-conserved Kit+/+ mice and -deficient KitW/KitW-v mice. The outcome of mast cell reconstitution was further investigated. Airway eosinophilia and IL-13 production were augmented by poly IC in Kit+/+ mice but not in KitW/KitW-v mice. When KitW/KitW-v mice were reconstituted with bone marrow-derived mast cells (BMMCs), the augmentation was restored. The augmentation was not induced in the mice systemically deficient for TIR domain-containing adaptor-inducing IFN-β (TRIF) or interferon regulatory factor (IRF)-3, both mediate dsRNA-triggered innate immune responses. The augmentation was, however, restored in KitW/KitW-v mice reconstituted with TRIF-deficient or IRF-3-deficient BMMCs. Although leukotriene B4 and prostaglandin D2 are major lipid mediators released from activated mast cells, no their contribution was shown to the dsRNA-induced augmentation of airway eosinophilia. We conclude that mast cells contribute to dsRNA-induced augmentation of allergic airway inflammation without requiring direct activation of mast cells with dsRNA or involvement of leukotriene B4 or prostaglandin D2.

  5. The signal transduction pathway in the proliferation of airway smooth muscle cells induced by urotensin Ⅱ

    Institute of Scientific and Technical Information of China (English)

    陈亚红; 赵鸣武; 姚婉贞; 庞永政; 唐朝枢

    2004-01-01

    Background Human urotensin Ⅱ (UⅡ) is the most potent mammalian vasoconstrictor identified so far. Our previous study showed that UⅡ is a potent mitogen of airway smooth muscle cells (ASMC) inducing ASMC proliferation in a dose-dependent manner. The signal transduction pathway of UⅡ mitogenic effect remains to be clarified. This study was conducted to investigate the signal transduction pathway in the proliferation of ASMC induced by UⅡ.Methods In primary cultures of rat ASMCs, activities of protein kinase C (PKC), mitogen-activated protein kinase (MAPK) and calcineurin (CaN) induced by UⅡ were measured. The effect of CaN on PKC and MAPK was studied by adding cyclosporin A (CsA), a specific inhibitor of CaN. Using H7 and PD98059, inhibitors of PKC and MAPK, respectively, to study the effect of PKC and MAPK on CaN. The cytosolic free calcium concentration induced by UⅡ was measured using Fura-2/AM. Results UⅡ 10-7 mol/L stimulated ASMC PKC and MAPK activities by 44% and 24% (P0.05). CsA 10-6 mol/L inhibited UⅡ-stimulated PKC activity by 14% (P0.05).Conclusions UⅡ increases cytosolic free calcium concentration and activates PKC, MAPK and CaN. The signal transduction pathway between PKC and CaN has cross-talk.

  6. Role of 5-hydroxytryptamine in mediating adenosine-induced airway contraction.

    Science.gov (United States)

    Matera, M G; De Santis, D; D'Agostino, B; Pallotta, M; Vacca, C; Cazzola, M; Rossi, F

    1995-02-01

    We have investigated the role of 5-hydroxytryptamine (5-HT) on adenosine-induced guinea-pig trachea contraction. R-N6-phenylisopropyladenosine (R-PIA), an A1 receptor subtype agonist, induced a concentration-dependent contraction of tracheal rings. The pD2 values were 7.43 +/- 0.26. A 30-min pretreatment with 1,3-dipropyl-8-amino-4-clorophenylxantine (PACPX), a selective A1 receptor antagonist, shifted to the right the R-PIA concentration effect curves. Ketanserin (1 microM), a 5-HT2 receptor antagonist, also caused a rightward shift of the R-PIA concentration-effect curves. The changes for the pD2 values comparing the controls and the tissues incubated with ketanserin were statistically significant (P diphenydramine (1 microM), nor indomethacin (5 microM) showed any effects. The challenge of R-PIA (1 microM) with said substances induced a release of 5-HT (4.8 +/- 0.20 fmol/ml) from guinea-pig trachea in presence or in absence of epithelium; in the same experimental conditions, this effect did not occur in the controls. Our data support the hypothesis that 5-HT plays a role in adenosine-induced airway contraction.

  7. Cyclic mechanical strain-induced proliferation and migration of human airway smooth muscle cells: role of EMMPRIN and MMPs.

    Science.gov (United States)

    Hasaneen, Nadia A; Zucker, Stanley; Cao, Jian; Chiarelli, Christian; Panettieri, Reynold A; Foda, Hussein D

    2005-09-01

    Airway smooth muscle (ASM) proliferation and migration are major components of airway remodeling in asthma. Asthmatic airways are exposed to mechanical strain, which contributes to their remodeling. Matrix metalloproteinase (MMP) plays an important role in remodeling. In the present study, we examined if the mechanical strain of human ASM (HASM) cells contributes to their proliferation and migration and the role of MMPs in this process. HASM were exposed to mechanical strain using the FlexCell system. HASM cell proliferation, migration and MMP release, activation, and expression were assessed. Our results show that cyclic strain increased the proliferation and migration of HASM; cyclic strain increased release and activation of MMP-1, -2, and -3 and membrane type 1-MMP; MMP release was preceded by an increase in extracellular MMP inducer; Prinomastat [a MMP inhibitor (MMPI)] significantly decreased cyclic strain-induced proliferation and migration of HASM; and the strain-induced increase in the release of MMPs was accompanied by an increase in tenascin-C release. In conclusion, cyclic mechanical strain plays an important role in HASM cell proliferation and migration. This increase in proliferation and migration is through an increase in MMP release and activation. Pharmacological MMPIs should be considered in the pursuit of therapeutic options for airway remodeling in asthma.

  8. Up-regulation of endothelin receptors induced by cigarette smoke--involvement of MAPK in vascular and airway hyper-reactivity

    DEFF Research Database (Denmark)

    Zhang, Yaping; Edvinsson, Lars; Xu, Cang-Bao

    2010-01-01

    and airway diseases. In the vasculature and airways, the main functional consequences of up-regulated endothelin receptors by cigarette smoke exposure are enhanced contraction and proliferation of the smooth muscle cells, which subsequently result in abnormal contraction (spasm) and adverse proliferation......Cigarette smoke exposure is well known to cause cardiovascular and airway diseases, both of which are leading causes of death and disability in the world. However, the molecular mechanisms that link cigarette smoke to cardiovascular and airway diseases are not fully understood. Vascular and airway...... (remodeling) of the vasculature and airways. The structural alteration by adverse remodeling involves changes in cell growth, cell death, cell migration, and production or degradation of the extracellular matrix. This review focuses on cigarette smoke exposure that induces activation of intracellular mitogen...

  9. Protective Roles for RGS2 in a Mouse Model of House Dust Mite-Induced Airway Inflammation

    Science.gov (United States)

    George, Tresa; Bell, Matthew; Chakraborty, Mainak; Siderovski, David P.; Giembycz, Mark A.

    2017-01-01

    The GTPase-accelerating protein, regulator of G-protein signalling 2 (RGS2) reduces signalling from G-protein-coupled receptors (GPCRs) that signal via Gαq. In humans, RGS2 expression is up-regulated by inhaled corticosteroids (ICSs) and long-acting β2-adrenoceptor agonists (LABAs) such that synergy is produced in combination. This may contribute to the superior clinical efficacy of ICS/LABA therapy in asthma relative to ICS alone. In a murine model of house dust mite (HDM)-induced airways inflammation, three weeks of intranasal HDM (25 μg, 3×/week) reduced lung function and induced granulocytic airways inflammation. Compared to wild type animals, Rgs2-/- mice showed airways hyperresponsiveness (increased airways resistance and reduced compliance). While HDM increased pulmonary inflammation observed on hematoxylin and eosin-stained sections, there was no difference between wild type and Rgs2-/- animals. HDM-induced mucus hypersecretion was also unaffected by RGS2 deficiency. However, inflammatory cell counts in the bronchoalveolar lavage fluid of Rgs2-/- animals were significantly increased (57%) compared to wild type animals and this correlated with increased granulocyte (neutrophil and eosinophil) numbers. Likewise, cytokine and chemokine (IL4, IL17, IL5, LIF, IL6, CSF3, CXCLl, CXCL10 and CXCL11) release was increased by HDM exposure. Compared to wild type, Rgs2-/- animals showed a trend towards increased expression for many cytokines/chemokines, with CCL3, CCL11, CXCL9 and CXCL10 being significantly enhanced. As RGS2 expression was unaffected by HDM exposure, these data indicate that RGS2 exerts tonic bronchoprotection in HDM-induced airways inflammation. Modest anti-inflammatory and anti-remodelling roles for RGS2 are also suggested. If translatable to humans, therapies that maximize RGS2 expression may prove advantageous. PMID:28107494

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

    OpenAIRE

    2010-01-01

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

  11. Hydrogen sulfide inhalation ameliorates allergen induced airway hypereactivity by modulating mast cell activation.

    Science.gov (United States)

    Roviezzo, Fiorentina; Bertolino, Antonio; Sorrentino, Rosalinda; Terlizzi, Michela; Matteis, Maria; Calderone, Vincenzo; Mattera, Valentina; Martelli, Alma; Spaziano, Giuseppe; Pinto, Aldo; D'Agostino, Bruno; Cirino, Giuseppe

    2015-10-01

    Compelling evidence suggests that hydrogen sulfide represents an important gaseous transmitter in the mammalian respiratory system. In the present study, we have evaluated the role of mast cells in hydrogen sulfide-induced effects on airways in a mouse model of asthma. Mice were sensitized to ovalbumin and received aerosol of a hydrogen sulfide donor (NaHS; 100 ppm) starting at day 7 after ovalbumin challenge. Exposure to hydrogen sulfide abrogated ovalbumin-induced bronchial hypereactivity as well as the increase in lung resistance. Concomitantly, hydrogen sulfide prevented mast cell activity as well as FGF-2 and IL-13 upregulation. Conversely, pulmonary inflammation and the increase in plasmatic IgE levels were not affected by hydrogen sulfide. A lack of hydrogen sulfide effects in mast cell deficient mice occurred. Primary fibroblasts harvested from ovalbumin-sensitized mice showed an increased proliferation rate that was inhibited by hydrogen sulfide aerosol. Furthermore, ovalbumin-induced transdifferentiation of pulmonary fibroblasts into myofibroblasts was reversed. Finally, hydrogen sulfide did abrogate in vitro the degranulation of the mast cell-like RBL-2H3 cell line. Similarly to the in vivo experiments the inhibitory effect was present only when the cells were activated by antigen exposure. In conclusion, inhaled hydrogen sulfide improves lung function and inhibits bronchial hyper-reactivity by modulating mast cells and in turn fibroblast activation.

  12. Airway epithelial inflammation-induced endoplasmic reticulum Ca2+ store expansion is mediated by X-box binding protein-1.

    Science.gov (United States)

    Martino, Mary E B; Olsen, John C; Fulcher, Nanette B; Wolfgang, Matthew C; O'Neal, Wanda K; Ribeiro, Carla M P

    2009-05-29

    Inflamed cystic fibrosis (CF) human bronchial epithelia (HBE), or normal HBE exposed to supernatant from mucopurulent material (SMM) from CF airways, exhibit endoplasmic reticulum (ER)/Ca(2+) store expansion and amplified Ca(2+)-mediated inflammation. HBE inflammation triggers an unfolded protein response (UPR) coupled to mRNA splicing of X-box binding protein-1 (XBP-1). Because spliced XBP-1 (XBP-1s) promotes ER expansion in other cellular models, we hypothesized that XBP-1s is responsible for the ER/Ca(2+) store expansion in inflamed HBE. XBP-1s was increased in freshly isolated infected/inflamed CF in comparison with normal HBE. The link between airway epithelial inflammation, XBP-1s, and ER/Ca(2+) store expansion was then addressed in murine airways challenged with phosphate-buffered saline or Pseudomonas aeruginosa. P. aeruginosa-challenged mice exhibited airway epithelial ER/Ca(2+) store expansion, which correlated with airway inflammation. P. aeruginosa-induced airway inflammation triggered XBP-1s in ER stress-activated indicator (ERAI) mice. To evaluate the functional role of XBP-1s in airway inflammation linked to ER/Ca(2+) store expansion, control, XBP-1s, or dominant negative XBP-1 (DN-XBP-1) stably expressing 16HBE14o(-) cell lines were used. Studies with cells transfected with an unfolded protein response element (UPRE) luciferase reporter plasmid confirmed that the UPRE was activated or inhibited by expression of XBP-1s or DN-XBP-1, respectively. Expression of XBP-1s induced ER/Ca(2+) store expansion and potentiated bradykinin-increased interleukin (IL)-8 secretion, whereas expression of DN-XBP-1 inhibited bradykinin-dependent IL-8 secretion. In addition, expression of DN-XBP-1 blunted SMM-induced ER/Ca(2+) store expansion and SMM-induced IL-8 secretion. These findings suggest that, in inflamed HBE, XBP-1s is responsible for the ER/Ca(2+) store expansion that confers amplification of Ca(2+)-dependent inflammatory responses.

  13. Programmed Death Ligand 1 Promotes Early-Life Chlamydia Respiratory Infection-Induced Severe Allergic Airway Disease.

    Science.gov (United States)

    Starkey, Malcolm R; Nguyen, Duc H; Brown, Alexandra C; Essilfie, Ama-Tawiah; Kim, Richard Y; Yagita, Hideo; Horvat, Jay C; Hansbro, Philip M

    2016-04-01

    Chlamydia infections are frequent causes of respiratory illness, particularly pneumonia in infants, and are linked to permanent reductions in lung function and the induction of asthma. However, the immune responses that protect against early-life infection and the mechanisms that lead to chronic lung disease are incompletely understood. In the current study, we investigated the role of programmed death (PD)-1 and its ligands PD-L1 and PD-L2 in promoting early-life Chlamydia respiratory infection, and infection-induced airway hyperresponsiveness (AHR) and severe allergic airway disease in later life. Infection increased PD-1 and PD-L1, but not PD-L2, mRNA expression in the lung. Flow cytometric analysis of whole lung homogenates identified monocytes, dendritic cells, CD4(+), and CD8(+) T cells as major sources of PD-1 and PD-L1. Inhibition of PD-1 and PD-L1, but not PD-L2, during infection ablated infection-induced AHR in later life. Given that PD-L1 was the most highly up-regulated and its targeting prevented infection-induced AHR, subsequent analyses focused on this ligand. Inhibition of PD-L1 had no effect on Chlamydia load but suppressed infection-induced pulmonary inflammation. Infection decreased the levels of the IL-13 decoy receptor in the lung, which were restored to baseline levels by inhibition of PD-L1. Finally, inhibition of PD-L1 during infection prevented subsequent infection-induced severe allergic airways disease in later life by decreasing IL-13 levels, Gob-5 expression, mucus production, and AHR. Thus, early-life Chlamydia respiratory infection-induced PD-L1 promotes severe inflammation during infection, permanent reductions in lung function, and the development of more severe allergic airway disease in later life.

  14. DMF inhibits PDGF-BB induced airway smooth muscle cell proliferation through induction of heme-oxygenase-1

    Directory of Open Access Journals (Sweden)

    Tamm Michael

    2010-10-01

    Full Text Available Abstract Background Airway wall remodelling is an important pathology of asthma. Growth factor induced airway smooth muscle cell (ASMC proliferation is thought to be the major cause of airway wall thickening in asthma. Earlier we reported that Dimethylfumarate (DMF inhibits platelet-derived growth factor (PDGF-BB induced mitogen and stress activated kinase (MSK-1 and CREB activity as well as IL-6 secretion by ASMC. In addition, DMF altered intracellular glutathione levels and thereby reduced proliferation of other cell types. Methods We investigated the effect of DMF on PDGF-BB induced ASMC proliferation, on mitogen activated protein kinase (MAPK activation; and on heme oxygenase (HO-1 expression. ASMC were pre-incubated for 1 hour with DMF and/or glutathione ethylester (GSH-OEt, SB203580, hemin, cobalt-protoporphyrin (CoPP, or siRNA specific to HO-1 before stimulation with PDGF-BB (10 ng/ml. Results PDGF-BB induced ASMC proliferation was inhibited in a dose-dependant manner by DMF. PDGF-BB induced the phosphorylation of ERK1/2 and p38 MAPK, but not of JNK. DMF enhanced the PDGF-BB induced phosphorylation of p38 MAPK and there by up-regulated the expression of HO-1. HO-1 induction inhibited the proliferative effect of PDGF-BB. HO-1 expression was reversed by GSH-OEt, or p38 MAPK inhibition, or HO-1 siRNA, which all reversed the anti-proliferative effect of DMF. Conclusion Our data indicate that DMF inhibits ASMC proliferation by reducing the intracellular GSH level with subsequent activation of p38 MAPK and induction of HO-1. Thus, DMF might reduce ASMC and airway remodelling processes in asthma.

  15. Short-term smoke exposure attenuates ovalbumin-induced airway inflammation in allergic mice

    NARCIS (Netherlands)

    Melgert, BN; Postma, DS; Geerlings, M; Luinge, MA; Klok, PA; van der Strate, BWA; Kerstjens, HAM; Timens, W; Hylkema, MN

    Little is known about effects of smoking on airway inflammation in asthma. We tested the hypothesis that smoking enhances established airway inflammation in a mouse model of allergic asthma. C57Bl/6j mice were sensitized to ovalbumin (OVA) and challenged with OVA (OVA-mice) or sham-sensitized to

  16. Insulin-Induced Laminin Expression Promotes a Hypercontractile Airway Smooth Muscle Phenotype

    NARCIS (Netherlands)

    Dekkers, Bart G. J.; Schaafsma, Dedmer; Tran, Thai; Zaagsma, Johan; Meurs, Herman

    2009-01-01

    Airway smooth muscle (ASM) plays a key role in the development of airway hyperresponsiveness and remodeling in asthma, which may involve maturation of ASM cells to a hypercontractile phenotype. In vitro studies have indicated that long-term exposure of bovine tracheal smooth muscle (BTSM) to insulin

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

    Directory of Open Access Journals (Sweden)

    J. R. Lapa e Silva

    1999-01-01

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

  18. PPARγ ligand ciglitazone inhibits TNFα-induced ICAM-1 in human airway smooth muscle cells

    Directory of Open Access Journals (Sweden)

    Chien-Da Huang

    2014-08-01

    Full Text Available Background: Modification of human airway smooth muscle (ASM function by proinflammatory cytokines has been regarded as a potential mechanism underlying bronchial hyperresponsiveness in asthma. Human ASM cells express intercellular adhesion molecule (ICAM-1 in response to cytokines. Synthetic ligands for peroxisome proliferator-activated receptor (PPARγ reportedly possess anti-inflammatory and immunomodulatory properties. In this study, we examined whether ciglitazone, a synthetic PPARγ ligand, can modulate the basal and tumor necrosis factor (TNFα-induced ICAM1 gene expression in human ASM cells. Methods: Human ASM cells were treated with TNFα. ICAM-1 expression was assessed by flow cytometry and reverse transcriptase-polymerase chain reaction (RT-PCR analysis. PPARγ activity was inhibited by target-specific small interfering (si RNA targeting PPARγ and GW9662, a PPARγ antagonist. Activity of nuclear factor (NF-κB was assessed by using immunoblot analysis, immune-confocal images, and electrophoretic mobility shift assay (EMSA. Results: By flow cytometry, ciglitazone alone had no effect on ICAM-1 expression in ASM cells, but inhibited ICAM-1 expression in response to TNFα (10 ng/ml in a dose-dependent manner (1-10 μM. It also inhibited TNFα-induced ICAM1 gene expression by RT-PCR analysis. Knockdown of PPARγ gene by target-specific siRNA targeting PPARγ enhanced ICAM-1 expression and the inhibitory effect of ciglitazone on TNFα-induced ICAM-1 expression was reversed by PPARγ siRNA and GW9662. SN-50 (10 μg/ml, an inhibitor for nuclear translocation of NF-κB, inhibited TNFα-induced ICAM-1 expression. Ciglitazone did not prevent TNFα-induced degradation of the cytosolic inhibitor of NF-κB (IκB, but inhibited the nuclear translocation of p65 induced by TNFα and suppressed the NF-κB/DNA binding activity. Conclusion: These findings suggest that ciglitazone inhibits TNFα-induced ICAM1 gene expression in human ASM cells through

  19. Intranasal organic dust exposure-induced airway adaptation response marked by persistent lung inflammation and pathology in mice

    OpenAIRE

    Poole, Jill A.; Wyatt, Todd A; Oldenburg, Peter J.; Elliott, Margaret K.; West, William W.; Sisson, Joseph H.; Von Essen, Susanna G.; Romberger, Debra J.

    2009-01-01

    Organic dust exposure in agricultural environments results in an inflammatory response that attenuates over time, but repetitive exposures can result in chronic respiratory disease. Animal models to study these mechanisms are limited. This study investigated the effects of single vs. repetitive dust-induced airway inflammation in mice by intranasal exposure method. Mice were exposed to swine facility dust extract (DE) or saline once and once daily for 1 and 2 wk. Dust exposure resulted in inc...

  20. Glyphosate–rich air samples induce IL–33, TSLP and generate IL–13 dependent airway inflammation

    Science.gov (United States)

    Kumar, Sudhir; Khodoun, Marat; Kettleson, Eric M.; McKnight, Christopher; Reponen, Tiina; Grinshpun, Sergey A.; Adhikari, Atin

    2014-01-01

    Several low weight molecules have often been implicated in the induction of occupational asthma. Glyphosate, a small molecule herbicide, is widely used in the world. There is a controversy regarding a role of glyphosate in developing asthma and rhinitis among farmers, the mechanism of which is unexplored. The aim of this study was to explore the mechanisms of glyphosate induced pulmonary pathology by utilizing murine models and real environmental samples. C57BL/6, TLR4−/−, and IL-13−/− mice inhaled extracts of glyphosate-rich air samples collected on farms during spraying of herbicides or inhaled different doses of glyphosate and ovalbumin. The cellular response, humoral response, and lung function of exposed mice were evaluated. Exposure to glyphosate-rich air samples as well as glyphosate alone to the lungs increased: eosinophil and neutrophil counts, mast cell degranulation, and production of IL-33, TSLP, IL-13, and IL-5. In contrast, in vivo systemic IL-4 production was not increased. Co-administration of ovalbumin with glyphosate did not substantially change the inflammatory immune response. However, IL-13-deficiency resulted in diminished inflammatory response but did not have a significant effect on airway resistance upon methacholine challenge after 7 or 21 days of glyphosate exposure. Glyphosate-rich farm air samples as well as glyphosate alone were found to induce pulmonary IL-13-dependent inflammation and promote Th2 type cytokines, but not IL-4 for glyphosate alone. This study, for the first time, provides evidence for the mechanism of glyphosate-induced occupational lung disease. PMID:25172162

  1. Glyphosate-rich air samples induce IL-33, TSLP and generate IL-13 dependent airway inflammation.

    Science.gov (United States)

    Kumar, Sudhir; Khodoun, Marat; Kettleson, Eric M; McKnight, Christopher; Reponen, Tiina; Grinshpun, Sergey A; Adhikari, Atin

    2014-11-01

    Several low weight molecules have often been implicated in the induction of occupational asthma. Glyphosate, a small molecule herbicide, is widely used in the world. There is a controversy regarding a role of glyphosate in developing asthma and rhinitis among farmers, the mechanism of which is unexplored. The aim of this study was to explore the mechanisms of glyphosate induced pulmonary pathology by utilizing murine models and real environmental samples. C57BL/6, TLR4-/-, and IL-13-/- mice inhaled extracts of glyphosate-rich air samples collected on farms during spraying of herbicides or inhaled different doses of glyphosate and ovalbumin. The cellular response, humoral response, and lung function of exposed mice were evaluated. Exposure to glyphosate-rich air samples as well as glyphosate alone to the lungs increased: eosinophil and neutrophil counts, mast cell degranulation, and production of IL-33, TSLP, IL-13, and IL-5. In contrast, in vivo systemic IL-4 production was not increased. Co-administration of ovalbumin with glyphosate did not substantially change the inflammatory immune response. However, IL-13-deficiency resulted in diminished inflammatory response but did not have a significant effect on airway resistance upon methacholine challenge after 7 or 21 days of glyphosate exposure. Glyphosate-rich farm air samples as well as glyphosate alone were found to induce pulmonary IL-13-dependent inflammation and promote Th2 type cytokines, but not IL-4 for glyphosate alone. This study, for the first time, provides evidence for the mechanism of glyphosate-induced occupational lung disease.

  2. Reciprocal immunomodulatory effects of gamma interferon and interleukin-4 on filaria-induced airway hyperresponsiveness.

    Science.gov (United States)

    Mehlotra, R K; Hall, L R; Haxhiu, M A; Pearlman, E

    2001-03-01

    Tropical pulmonary eosinophilia (TPE) is a severe asthmatic syndrome of lymphatic filariasis, in which an allergic response is induced to microfilariae (Mf) in the lungs. Previously, in a murine model for TPE, we have demonstrated that recombinant interleukin-12 (IL-12) suppresses pulmonary eosinophilia and airway hyperresponsiveness (AHR) by modulating the T helper (Th) response in the lungs from Th2- to Th1-like, with elevated gamma-interferon (IFN-gamma) production and decreased IL-4 and IL-5 production. The present study examined the immunomodulatory roles of IL-4 and IFN-gamma in filaria-induced AHR and pulmonary inflammation using mice genetically deficient in these cytokines. C57BL/6, IL-4 gene knockout (IL-4(-/-)), and IFN-gamma(-/-) mice were first immunized with soluble Brugia malayi antigens and then inoculated intravenously with 200,000 live Mf. Compared with C57BL/6 mice, IL-4(-/-) mice exhibited significantly reduced AHR, whereas IFN-gamma(-/-) mice had increased AHR. Histopathologically, each mouse strain showed increased cellular infiltration into the lung parenchyma and bronchoalveolar space compared with naïve animals. However, consistent with changes in AHR, IL-4(-/-) mice had less inflammation than C57BL/6 mice, whereas IFN-gamma(-/-) mice had exacerbated pulmonary inflammation with the loss of pulmonary architecture. Systemically, IL-4(-/-) mice produced significantly higher IFN-gamma levels compared with C57BL/6 mice, whereas IFN-gamma(-/-) mice produced significantly higher IL-4 levels. These data indicate that IL-4 is required for the induction of filaria-induced AHR, whereas IFN-gamma suppresses AHR.

  3. Comparative evaluation of incidence of emergence agitation and post-operative recovery profile in paediatric patients after isoflurane, sevoflurane and desflurane anaesthesia

    Directory of Open Access Journals (Sweden)

    Rahil Singh

    2012-01-01

    Full Text Available Background: Emergence agitation (EA, although well documented in the clinical literature, still has uncertainties and confusion abound on this subject because of the absence of a clear definition and lack of reliable and valid assessment tools. Aim: To compare the incidence and severity of EA and recovery characteristics in paediatric patients under isoflurane, sevoflurane or desflurane anaesthesia and evaluate the effect of age and duration of anaesthesia on the incidence of EA. Settings and Design: Randomized prospective double-blinded study. Methods: Seventy-five American Society of Anaesthesiologists I and II patients, aged between 4 months and 7 years, were included in the study. Patients were induced with sevoflurane and oxygen. Anaesthesia was maintained with O 2 + N 2 O and isoflurane, sevoflurane or desflurane according to randomization. Caudal block and paracetamol suppository was administered before the surgical incision. In the Post-Anesthesia Care Unit (PACU, degree of agitation was assessed using the Paediatric Anaesthesia Emergence Delirium Scale. Aldrette score, Face, Legs, Activity, Cry, Consolability score and any adverse events were noted. Statistical Analysis: Chi-square/Fischer exact test was applied for categorical variables; for continuous variables, the analysis of variance/non-parametric Kruskall-Wallis test was applied. Two-sample t-test/non-parametric Wisconsin Mann-Whitney test was applied between the two groups. Statistical significance was determined at P<0.05. Results: Incidence and intensity of EA were comparable in all three groups. Age and duration of anaesthesia do not appear to have any bearing on the incidence of EA. Rapid emergence with sevoflurane and desflurane did not translate into early discharge from PACU. Conclusions: EA is a multifactorial syndrome. More well-conducted studies using validated scales and standardized protocols should be carried out to better understand this phenomenon.

  4. A comparison of the effects of desflurane versus propofol on transcranial motor-evoked potentials in pediatric patients.

    Science.gov (United States)

    Holdefer, Robert N; Anderson, Corrie; Furman, Michele; Sangare, Yoro; Slimp, Jefferson C

    2014-12-01

    The aim was to compare the effects of propofol and desflurane anesthesia on transcranial motor evoked potentials (MEPs) from pediatric patients undergoing surgery for spinal deformities. Desflurane and propofol cohorts (25 patients each) were obtained retrospectively and matched for patient characteristics and surgical approach. MEPs from the thenar eminence and abductor hallucis were compared during maintenance anesthesia on desflurane (0.6-0.8 MAC) or propofol infusion (150-300 μg/kg/min). MEP amplitudes and durations were obtained for successive 30-min intervals for 150 min, beginning 60 min after maintenance anesthesia. Mean peak to peak amplitudes of MEPs under desflurane anesthesia from the thenar eminence (419 μV) and abductor hallucis (386 μv) were not significantly different from those under propofol (608 μV, 343 μV, thenar, and abductor hallucis, respectively). Stimulation was greater by 42 V and 136 mA, and trains were slightly longer in the desflurane compared to the propofol group (p propofol cohorts remained the same or increased (71 % of cases) when those after 150 min were compared to those in the first 30-min interval. MEPs with good amplitudes were obtained under desflurane only anesthesia that were comparable to propofol only anesthesia in pediatric patients during surgery for spinal deformities. There was no evidence for anesthetic fade over the time period examined. When used by itself, desflurane can be considered a viable alternative to propofol anesthesia.

  5. A single dose of esmolol blunts the increase in bispectral index to tracheal intubation during sevoflurane but not desflurane anesthesia.

    Science.gov (United States)

    Choi, Seung Ho; Kim, Chang Seok; Kim, Jong Hoon; Kim, Bum Su; Kim, Eun Mi; Min, Kyeong Tae

    2009-07-01

    Activation of the peripheral nerve system by endotracheal intubation is accompanied by an increase in bispectral index (BIS). Esmolol produces a dose-dependent attenuation of the adrenergic response to endotracheal intubation. Desflurane increases sympathetic nerve activity and plasma norepinephrine relative to sevoflurane. The authors hypothesized that esmolol might blunt the BIS response to endotracheal intubation more during sevoflurane anesthesia than desflurane anesthesia. In this double blind, randomized study, after the induction of anesthesia, patients were mask-ventilated with either sevoflurane or desflurane (end-tidal 1 minimum alveolar concentration) and received normal saline or esmolol (0.5 mg/kg) 1 minute before intubation (sevoflurane-control, sevoflurane-esmolol, desflurane-control, and desflurane-esmolol groups, n=20/group). BIS, mean arterial pressure, and heart rate were measured before the induction of anesthesia (awake), before esmolol injection (time point -1), immediately before intubation (time point 0), and every minute for 5 minutes after tracheal intubation (time point 1 to 5). Compared with preintubation, esmolol attenuated the increase in BIS at 1 minute after intubation during sevoflurane anesthesia (5.1% for esmolol and 31.7% for control) but not during desflurane anesthesia (28.6% for esmolol and 30.8% for control). Mean arterial pressure and heart rate increased after intubation in all groups but the changes were greater in the control groups than the esmolol groups. In conclusion, a single dose of esmolol blunted the increase in BIS to tracheal intubation during sevoflurane but not desflurane anesthesia.

  6. Environmentally persistent free radicals induce airway hyperresponsiveness in neonatal rat lungs

    Directory of Open Access Journals (Sweden)

    Lominiki Slawo

    2011-03-01

    Full Text Available Abstract Background Increased asthma risk/exacerbation in children and infants is associated with exposure to elevated levels of ultrafine particulate matter (PM. The presence of a newly realized class of pollutants, environmentally persistent free radicals (EPFRs, in PM from combustion sources suggests a potentially unrecognized risk factor for the development and/or exacerbation of asthma. Methods Neonatal rats (7-days of age were exposed to EPFR-containing combustion generated ultrafine particles (CGUFP, non-EPFR containing CGUFP, or air for 20 minutes per day for one week. Pulmonary function was assessed in exposed rats and age matched controls. Lavage fluid was isolated and assayed for cellularity and cytokines and in vivo indicators of oxidative stress. Pulmonary histopathology and characterization of differential protein expression in lung homogenates was also performed. Results Neonates exposed to EPFR-containing CGUFP developed significant pulmonary inflammation, and airway hyperreactivity. This correlated with increased levels of oxidative stress in the lungs. Using differential two-dimensional electrophoresis, we identified 16 differentially expressed proteins between control and CGUFP exposed groups. In the rats exposed to EPFR-containing CGUFP; peroxiredoxin-6, cofilin1, and annexin A8 were upregulated. Conclusions Exposure of neonates to EPFR-containing CGUFP induced pulmonary oxidative stress and lung dysfunction. This correlated with alterations in the expression of various proteins associated with the response to oxidative stress and the regulation of glucocorticoid receptor translocation in T lymphocytes.

  7. Mometasone Furoate Suppresses PMA-Induced MUC-5AC and MUC-2 Production in Human Airway Epithelial Cells

    Science.gov (United States)

    Koontongkaew, Sittichai; Monthanapisut, Paopanga; Pattanacharoenchai, Napaporn

    2017-01-01

    Background Mucus hypersecretion from airway epithelium is a characteristic feature of airway inflammatory diseases. Tumor necrosis factor α (TNF-α) regulates mucin synthesis. Glucocorticoids including mometasone fuorate (MF) have been used to attenuate airway inflammation. However, effects of MF on mucin production have not been reported. Methods Effects of MF and budesonide (BUD) on the phorbol-12-myristate-13-acetate (PMA)–induction of mucin and TNF-α in human airway epithelial cells (NCI-H292) were investigated in the present study. Confluent NCI-H292 cells were pretreated with PMA (200 nM) for 2 hours. Subsequently, the cells were stimulated with MF (1–500 ng/mL) or BUD (21.5 ng/mL) for 8 hours. Dexamethasone (1 µg/mL) was used as the positive control. Real-time polymerase chain reaction was used to determine MUC2 and MUC5AC mRNA levels. The level of total mucin, MUC2, MUC5AC, and TNF-α in culture supernatants were measured using enzyme-linked immunosorbent assay. Results MF and BUD significantly suppressed MUC2 and MUC5AC gene expression in PMA-stimulated NCI-H292 cells. The inhibitory effects of the two steroid drugs were also observed in the production of total mucin, MUC2 and MUC5AC proteins, and TNF-α. Conclusion Our findings demonstrated that MF and BUD attenuated mucin and TNF-α production in PMA-induced human airway epithelial cells.

  8. ATP induced MUC5AC release from human airways in vitro

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    Patricia Roger

    2000-01-01

    Full Text Available Background: Chronic airway diseases are often associated with marked mucus production, however, little is known about the regulation of secretory activity by locally released endogenous mediators.

  9. IL-13–induced airway mucus production is attenuated by MAPK13 inhibition

    Science.gov (United States)

    Alevy, Yael G.; Patel, Anand C.; Romero, Arthur G.; Patel, Dhara A.; Tucker, Jennifer; Roswit, William T.; Miller, Chantel A.; Heier, Richard F.; Byers, Derek E.; Brett, Tom J.; Holtzman, Michael J.

    2012-01-01

    Increased mucus production is a common cause of morbidity and mortality in inflammatory airway diseases, including asthma, chronic obstructive pulmonary disease (COPD), and cystic fibrosis. However, the precise molecular mechanisms for pathogenic mucus production are largely undetermined. Accordingly, there are no specific and effective anti-mucus therapeutics. Here, we define a signaling pathway from chloride channel calcium-activated 1 (CLCA1) to MAPK13 that is responsible for IL-13–driven mucus production in human airway epithelial cells. The same pathway was also highly activated in the lungs of humans with excess mucus production due to COPD. We further validated the pathway by using structure-based drug design to develop a series of novel MAPK13 inhibitors with nanomolar potency that effectively reduced mucus production in human airway epithelial cells. These results uncover and validate a new pathway for regulating mucus production as well as a corresponding therapeutic approach to mucus overproduction in inflammatory airway diseases. PMID:23187130

  10. A novel thiol compound, N-acetylcysteine amide, attenuates allergic airway disease by regulating activation of NF-kappaB and hypoxia-inducible factor-1alpha.

    Science.gov (United States)

    Lee, Kyung Sun; Kim, So Ri; Park, Hee Sun; Park, Seoung Ju; Min, Kyung Hoon; Lee, Ka Young; Choe, Yeong Hun; Hong, Sang Hyun; Han, Hyo Jin; Lee, Young Rae; Kim, Jong Suk; Atlas, Daphne; Lee, Yong Chul

    2007-12-31

    Reactive oxygen species (ROS) play an important role in the pathogenesis of airway inflammation and hyperresponsiveness. Recent studies have demonstrated that antioxidants are able to reduce airway inflammation and hyperreactivity in animal models of allergic airway disease. A newly developed antioxidant, small molecular weight thiol compound, N-acetylcysteine amide (AD4) has been shown to increase cellular levels of glutathione and to attenuate oxidative stress related disorders such as Alzheimer's disease, Parkinson's disease, and multiple sclerosis. However, the effects of AD4 on allergic airway disease such as asthma are unknown. We used ovalbumin (OVA)-inhaled mice to evaluate the role of AD4 in allergic airway disease. In this study with OVA-inhaled mice, the increased ROS generation, the increased levels of Th2 cytokines and VEGF, the increased vascular permeability, the increased mucus production, and the increased airway resistance in the lungs were significantly reduced by the administration of AD4. We also found that the administration of AD4 decreased the increases of the NF-kappaB and hypoxia-inducible factor-1alpha (HIF-1alpha) levels in nuclear protein extracts of lung tissues after OVA inhalation. These results suggest that AD4 attenuates airway inflammation and hyperresponsiveness by regulating activation of NF-kappaB and HIF-1alpha as well as reducing ROS generation in allergic airway disease.

  11. Pharmacoeconomics of desflurane based minimal flow anesthesia for different durations of surgery

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    Habib M. R. Karim

    2016-12-01

    Conclusions: Desflurane consumption and cost do not depend on sex but on age, flow and time. It becomes more cost-effective for relatively longer duration of minimal flow anesthesia. [Int J Basic Clin Pharmacol 2016; 5(6.000: 2528-2533

  12. Effects of Sevoflurane and Desflurane Anesthesia on Recovery and Agitation in Children Undergoing Strabismus Surgery

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    Meziyet Sarac Ahrazoglu

    2012-08-01

    Full Text Available Purpose: We aimed to compared the effects of sevoflurane and desflurane anesthesia on recovery and early agitation in children undergoing strabismus surgery in our study. Method: Totally 42 patients undergoing elective strabismus surgery who between the ages of 2-10, ASA I-II were included this study. The patients were classified into two groups randomly. Induction of anesthesia was provided with 50% nitrous oxide, 50% oxygen and 6-8% sevoflurane in both groups. Maintenance of anesthesia was provided with sevoflurane 1-2% in Group I and desflurane 4-6% in Group II. The operation time, extubation, eye opening, obeying the verbal commands and orientation times and nausea-vomiting, laryngospasm and other adverse affects were recorded. Postoperative recovery (Modified Aldrete Emergence Score and agitation (Pediatric Anesthesia Delirium Scale and Watcha Behaviour Scale situation were recorded. Results: Patient’s demographic data and hemodynamic parameters were similar between the groups. Extubation, eye opening, obeying the verbal commands, orientation times were shorter in desflurane group than sevoflurane group(p< 0.05. Postoperative recovery and agitation scores were similar in two groups. Conclusion: In children, it was concluded that desflurane anesthesia may be preferred to sevoflurane because of shorter extubation, eye-opening, obeying the verbal commands and orientation times, but it did not reduce postoperative agitation. [Cukurova Med J 2012; 37(4.000: 186-192

  13. Neutralization of TSLP inhibits airway remodeling in a murine model of allergic asthma induced by chronic exposure to house dust mite.

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    Zhuang-Gui Chen

    Full Text Available Chronic allergic asthma is characterized by Th2-typed inflammation, and contributes to airway remodeling and the deterioration of lung function. However, the initiating factor that links airway inflammation to remodeling is unknown. Thymic stromal lymphopoietin (TSLP, an epithelium-derived cytokine, can strongly activate lung dendritic cells (DCs through the TSLP-TSLPR and OX40L-OX40 signaling pathways to promote Th2 differentiation. To determine whether TSLP is the underlying trigger of airway remodeling in chronic allergen-induced asthma, we induced allergic airway inflammation in mice by intranasal administration of house dust mite (HDM extracts for up to 5 consecutive weeks. We showed that repeated respiratory exposure to HDM caused significant airway eosinophilic inflammation, peribronchial collagen deposition, goblet cell hyperplasia, and airway hyperreactivity (AHR to methacholine. These effects were accompanied with a salient Th2 response that was characterized by the upregulation of Th2-typed cytokines, such as IL-4 and IL-13, as well as the transcription factor GATA-3. Moreover, the levels of TSLP and transforming growth factor beta 1 (TGF-β1 were also increased in the airway. We further demonstrated, using the chronic HDM-induced asthma model, that the inhibition of Th2 responses via neutralization of TSLP with an anti-TSLP mAb reversed airway inflammation, prevented structural alterations, and decreased AHR to methacholine and TGF-β1 level. These results suggest that TSLP plays a pivotal role in the initiation and persistence of airway inflammation and remodeling in the context of chronic allergic asthma.

  14. Inhibition of NF-κB Expression and Allergen-induced Airway Inflammation in a Mouse Allergic Asthma Model by Andrographolide

    Institute of Scientific and Technical Information of China (English)

    Jing Li; Li Luo; Xiaoyun Wang; Bin Liao; Guoping Li

    2009-01-01

    Andrographolide from traditional Chinese herbal medicines previously showed it possesses a strong anti-inflammatory activity. In present study, we investigated whether Andrographolide could inhibit allergen-induced airway inflammation and airways hyper-responsiveness and explored the mechanism of Andrographolide on allergen-induced airway inflammation and airways hyper-responsiveness. After sensitized and challenged by ovalbumin, the BALB/c mice were administered intraperitoneally with Andrographolide. Hyper-responsiveness was recorded. The lung tissues were assessed by histological examinations. NF-κB in lung was determined by immunofluorescence staining and Western blotting. Treatment of mice with Androqrapholide displayed lower Penh in response to asthma group mice. After treatment with Andrographolide, the extent of inflammation and cellular infltrafion in the airway were reduced. Andrographolide interrupted NF-κB to express in cell nucleus. The level of NF-κB expression was inhibited by Andrographolide. The data indicate that Andrographolide from traditional Chinese herbal medicines could inhibit extensive infiltration of inflammatory cells in lung and decrease airway hyperreactivity. Andrographolide could inhibit NF-κB expression in lung and suppress NF-κB expressed in the nucleus of airway epithelial cells. Cellular & Molecular Immunology. 2009;6(5):381-385.

  15. Synthesized OVA323-339MAP octamers mitigate OVA-induced airway inflammation by regulating Foxp3 T regulatory cells

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    Su Wen

    2012-07-01

    Full Text Available Abstract Background Antigen-specific immunotherapy (SIT has been widely practiced in treating allergic diseases such as asthma. However, this therapy may induce a series of allergic adverse events during treatment. Peptide immunotherapy (PIT was explored to overcome these disadvantages. We confirmed that multiple antigen peptides (MAPs do not cause autoimmune responses, which led to the presumption that MAPs intervention could alleviate allergic airway inflammation without inducing adverse effects. Results In this study, synthesized OVA323-339MAP octamers were subcutaneously injected into ovalbumin (OVA-sensitized and -challenged Balb/c mice to observe its effect on allergic airway inflammation, Th2 immune response, and immune regulating function. It was confirmed that OVA sensitization and challenge led to significant peritracheal inflammatory, cell infiltration, and intensive Th2 response. Treatment of OVA323-339MAP octomers in the airway inflammation mice model increased CD4+CD25+Foxp3+ T regulatory (Treg cells and their regulatory function in peripheral blood, mediastinal draining lymph nodes, and the spleen. Furthermore, OVA323-339MAP increased IL-10 levels in bronchial alveolar lavage fluid (BALF; up-regulated the expression of IL-10, membrane-bound TGF-β1, as well as Foxp3 in lung tissues; and up-regulated programmed death-1 (PD-1 and cytotoxic T lymphocyte associated antigen 4 (CTLA-4 on the surface of Treg cells. These results were further correlated with the decreased OVA specific immunoglobulin E (sIgE level and the infiltration of inflammatory cells such as eosinophils and lymphocytes in BALF. However, OVA323-339 peptide monomers did not show any of the mentioned effects in the same animal model. Conclusions Our study indicates that OVA323-339MAP had significant therapeutic effects on mice allergic airway inflammation by regulating the balance of Th1/Th2 response through Treg cells in vivo.

  16. Infection of Mice with Mycobacterium bovis–Bacillus Calmette-Guérin (BCG) Suppresses Allergen-induced Airway Eosinophilia

    Science.gov (United States)

    Erb, Klaus Josef; Holloway, John W.; Sobeck, Alexandra; Moll, Heidrun; Le Gros, Graham

    1998-01-01

    It has been proposed that the increase in prevalence and severity of atopic disorders inversely correlates with exposure to infectious diseases such as tuberculosis. We have investigated this issue by combining an intranasal Mycobacterium bovis–Bacillus Calmette-Guérin (BCG) infection with a murine model of allergen, (ovalbumin [OVA]) induced airway eosinophilia. BCG infection either 4 or 12 wk before allergen airway challenge resulted in a 90–95 and 60–70% reduction in eosinophilia within the lungs, respectively, compared to uninfected controls. The inhibition of airway eosinophilia correlated with a reduced level of IL-5 production by T cells from the lymph node draining the site of OVA challenge. Interestingly, BCG infection of the lung had no effect on IgG1 and IgE OVA-specific serum immunoglobulin or blood eosinophil levels. Furthermore, BCG-induced inhibition of airway eosinophilia was strongly reduced in interferon (IFN)-γ receptor–deficient mice and could be partially reversed by intranasal IL-5 application. Intranasal BCG infections could also reduce the degree of lung eosinophilia and IL-5 produced by T cells after Nippostrongylus brasiliensis infection. Taken together, our data suggest that IFN-γ produced during the T helper cell (Th)1 immune response against BCG suppresses the development of local inflammatory Th2 responses in the lung. Most importantly, this inhibition did not extend to the systemic immunoglobulin response against OVA. Our data support the view that mycobacterial infections have the potential to suppress the development of atopic disorders in humans. PMID:9463406

  17. Role of neutralizing anti-murine interleukin-17A monoclonal antibody on chronic ozone-induced airway inflammation in mice.

    Science.gov (United States)

    Zhang, Min; Fei, Xia; Zhang, Guo-Qing; Zhang, Peng-Yu; Li, Feng; Bao, Wu-Ping; Zhang, Ying-Ying; Zhou, Xin

    2016-10-01

    Exposure to ozone has led to airway inflammation and airway hyperresponsiveness, which potential mechanisms relate to ozone-induced oxidative stress. IL-17 is a growing target for autoimmune and inflammatory diseases. The aim of the study was to examine the inhibitory effects of anti-murine interleukin-17A monoclonal antibody (IL-17mAb) on adverse effects of ozone which are noted above. After C57/BL6 mice were exposed to ozone (2.5ppm; 3h) for 12 times over 6 weeks, IL-17mAb, PBS was intraperitoneally injected into mice 1h after ozone or air exposure for 6 weeks and mice were studied 24h after final exposure, monitoring bronchial responsiveness, airway inflammatory cells, lung histology, levels of neutrophil-related chemokine and proinflammatory cytokines in bronchoalveolar lavage (BAL) fluid and serum, the expression of IL-17A mRNA and protein, glucocorticoid receptors (GR), and the phosphorylation of p38MAPK in lung tissues. The administration of IL-17mAb reduced the ozone-induced increases in total cells, especially neutrophils; decreased levels of cytokines, including IL-8 in BAL fluid, IL-8 and IL-17A in serum; mitigated the severity of airway hyperresponsiveness; attenuated lung inflammation scores and histologic analysis confirmed the suppression of lung inflammation, compared with the administration of a control PBS. Exposure to ozone results in increases in IL-17A production rate, mRNA and protein levels of IL-17A and the protein level of GR. These effects were halted and reversed by IL-17mAb treatment. Furthermore, IL-17mAb also reduced the phosphorylation of p38MAPK. Therefore, we conclude that IL-17mAb may be a useful therapy in ozone-related diseases, including COPD.

  18. Inhibition of pan neurotrophin receptor p75 attenuates diesel particulate-induced enhancement of allergic airway responses in C57/B16J mice.

    Science.gov (United States)

    Farraj, Aimen K; Haykal-Coates, Najwa; Ledbetter, Allen D; Evansky, Paul A; Gavett, Stephen H

    2006-06-01

    Recent investigations have linked neurotrophins, including nerve growth factor (NGF), neurotrophin-3 (NT-3), and brain-derived neurotrophic factor (BDNF), to allergic airways diseases. Antibody blockade of NGF attenuates airway resistance in allergic mice. Diesel exhaust particle (DEP) exposure has been linked to asthma exacerbation in many cities with vehicular traffic congestion. We tested the hypothesis that DEP-induced enhancement of the hallmark features of allergic airway disease in a murine model is dependent on the function of the pan neurotrophin receptor p75. Ovalbumin (OVA)-sensitized C57B1/6J mice were intranasally instilled with an antibody against the p75 receptor or saline alone 1 h before OVA challenge. The mice were then exposed nose-only to the PM2.5 fraction of SRM2975 DEP or air alone for 5 h beginning 1 h after OVA challenge. Two days later, air-exposed OVA-allergic mice developed a small but insignificant increase in methacholine-induced airflow obstruction relative to air-exposed, vehicle-sensitized mice. DEP-exposed OVA-allergic mice had a significantly greater degree of airway obstruction than all other groups. Instillation of anti-p75 significantly attenuated the DEP-induced increase in airway obstruction in OVA-allergic mice to levels similar to non-sensitized mice. The DEP-induced exacerbation of allergic airway responses may, in part, be mediated by neurotrophins.

  19. Protective effects of anisodamine on cigarette smoke extract-induced airway smooth muscle cell proliferation and tracheal contractility

    Energy Technology Data Exchange (ETDEWEB)

    Xu, Guang-Ni; Yang, Kai; Xu, Zu-Peng; Zhu, Liang; Hou, Li-Na; Qi, Hong; Chen, Hong-Zhuan, E-mail: hongzhuan_chen@hotmail.com; Cui, Yong-Yao, E-mail: yongyaocui@yahoo.com.cn

    2012-07-01

    Anisodamine, an antagonist of muscarinic acetylcholine receptors (mAChRs), has been used therapeutically to improve smooth muscle function, including microvascular, intestinal and airway spasms. Our previous studies have revealed that airway hyper-reactivity could be prevented by anisodamine. However, whether anisodamine prevents smoking-induced airway smooth muscle (ASM) cell proliferation remained unclear. In this study, a primary culture of rat ASM cells was used to evaluate an ASM phenotype through the ability of the cells to proliferate and express contractile proteins in response to cigarette smoke extract (CSE) and intervention of anisodamine. Our results showed that CSE resulted in an increase in cyclin D1 expression concomitant with the G0/G1-to-S phase transition, and high expression of M2 and M3. Functional studies showed that tracheal hyper-contractility accompanied contractile marker α-SMA high-expression. These changes, which occur only after CSE stimulation, were prevented and reversed by anisodamine, and CSE-induced cyclin D1 expression was significantly inhibited by anisodamine and the specific inhibitor U0126, BAY11-7082 and LY294002. Thus, we concluded that the protective and reversal effects and mechanism of anisodamine on CSE-induced events might involve, at least partially, the ERK, Akt and NF-κB signaling pathways associated with cyclin D1 via mAChRs. Our study validated that anisodamine intervention on ASM cells may contribute to anti-remodeling properties other than bronchodilation. -- Highlights: ► CSE induces tracheal cell proliferation, hyper-contractility and α-SMA expression. ► Anisodamine reverses CSE-induced tracheal hyper-contractility and cell proliferation. ► ERK, PI3K, and NF-κB pathways and cyclin D1 contribute to the reversal effect.

  20. Concentrations of desflurane and propofol that suppress response to command in humans.

    Science.gov (United States)

    Chortkoff, B S; Eger, E I; Crankshaw, D P; Gonsowski, C T; Dutton, R C; Ionescu, P

    1995-10-01

    The anesthetic concentration just suppressing appropriate response to command (minimum alveolar anesthetic concentration awake [MAC-awake] for volatile anesthetics or plasma concentration to prevent a response in 50% of patients [Cp50]-awake for intravenous anesthetics) provides three important measures. First, along with pharmacokinetics, the ratio of the awakening concentration to the anesthetizing concentration (MAC-awake/MAC or Cp50-awake/Cp50) determines time to awakening. Second, a correlation between MAC-awake and the anesthetic concentration sufficient to prevent learning suggests MAC-awake provides a surrogate measure of amnestic potency. Third, population values for MAC-awake provide evidence for or against commonality in anesthetic mechanisms. We studied 22 male volunteers twice to determine both MAC-awake for desflurane (2.60% +/- 0.46%) and Cp50-awake for propofol (2.69 +/- 0.56 microgram/mL). Awakening with desflurane occurs at a concentration closer to its anesthetizing concentration (36% of MAC) than propofol (18% of Cp50); that is, 1) desflurane requires less of a decrement in anesthetic concentration at the effect site for arousal; and 2) if MAC-awake (Cp50-awake) values reflect the concentrations providing amnesia, propofol is a more potent amnestic. Of interest, the dose response curves of desflurane and propofol were equivalently steep, a finding consistent with a common mechanism of action. In contrast, sensitivity of each volunteer to desflurane did not correlate with sensitivity to propofol (r2 < 0.01, P = 0.98) arguing against a common mechanism.

  1. Effects of desflurane and isoflurane on hepatic and renal functions and coagulation profile during donor hepatectomy.

    Science.gov (United States)

    Toprak, H I; Şahin, T; Aslan, S; Karahan, K; Şanli, M; Ersoy, M Ö

    2012-01-01

    We compared the effect of two inhalation anesthetics desflurane and isoflurane on postoperative hepatic and renal functions as well as coagulation profiles in living donors undergoing right hepatectomy. This study was performed on 80 patients who were randomly allocated to group D (desflurane, n = 40) or group I (isoflurane, n = 40) after Faculty Ethics Committee approval. After induction, isoflurane or desflurane was used with air/oxygen for anesthetic maintenance. The isoflurane or desflurane concentration was set at one minimum alveolar concentration (MAC). Remifentanil was infused for analgesia as well as cisatracurium. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), international normalized ratio (INR), albumin, total bilirubin, blood urea nitrogen, creatinine, platelet count, and hemoglobin levels were analyzed preoperatively at end of the operation, and on postoperative days (PODs) 1, 2, 3, 5, 7, and 30. Both AST and ALT differed significantly and continually except on POD 30. AST showed significant elevations from the end of the operation to POD 2 and ALT, from the end of the operation to POD 5 in group I compared with group D. INR was significantly higher from the end of the operation to POD 3 in group I and to POD 2 in group D. At the end of the operation as well as on POD 1 and POD 2, INR was significantly increased in group I compared with group D. Albumin level was significantly lower at the end of the operation in both groups, but it was not different. No patient developed hepatic or renal failure. Our study showed better postoperative hepatic tests and INR using desflurane than isoflurane at equivalent doses of 1 MAC in living donors undergoing right hepatectomy.

  2. Tracheobronchoscopic Assessment of Exercise-Induced Pulmonary Hemorrhage and Airway Inflammation in Barrel Racing Horses.

    Science.gov (United States)

    Léguillette, R; Steinmann, M; Bond, S L; Stanton, B

    2016-07-01

    Poor performance is often suspected to be associated with EIPH in barrel racing horses; however, there are no published reports of EIPH for this discipline. The prevalence of EIPH in barrel racing horses is also unknown. This study was performed to determine the prevalence of EIPH and signs of airway inflammation in barrel racing horses under normal racing conditions in Alberta. About 170 barrel racing horses. Observational cross-sectional study. Tracheobronchoscopic examinations were performed at least 30 minutes postrace. Video recordings were scored off-site independently by two observers for EIPH and tracheal mucus accumulation (TMA). Horses with an EIPH score ≥2 were not assessed for TMA. Interobserver agreement was calculated by weighted κ statistics. Run times, environmental variables, and clinical information were also recorded for analysis. 77/170 (45.3%) of horses examined showed evidence of EIPH (grade ≥ 1). Interobserver agreement was 0.94. 140/141 (99.3%) of horses assessed for TMA showed evidence of tracheal mucus accumulation (grade ≥ 1) with 104/141 (73.8%) having a TMA score ≥ 2. Interobserver agreement was 0.73. A weak positive association was found between EIPH scores and average run speed, the presence of cough at rest reported by the riders, increased recovery time, exercise intolerance, and outdoor pattern. The high prevalence of EIPH observed in the sampled population indicates that barrel racing induces substantial stress on the lungs. The presence of EIPH did not impact negatively on performance. Factors such as environmental dust and frequent traveling might have contributed to the high prevalence of TMA observed. Copyright © 2016 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1992-02-01

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

  4. Pro-inflammatory Cytokines Impair Vitamin D-induced Host Defense in Cultured Airway Epithelial Cells.

    Science.gov (United States)

    Schrumpf, Jasmijn A; Amatngalim, Gimano D; Veldkamp, Joris B; Verhoosel, Renate M; Ninaber, Dennis K; Ordonez, Soledad R; van der Does, Anne M; Haagsman, Henk P; Hiemstra, Pieter S

    2017-02-23

    Vitamin D is a regulator of host defense against infections and induces expression of the antimicrobial peptide hCAP18/LL-37. Vitamin D deficiency is associated with chronic inflammatory lung diseases and respiratory infections. However, it is incompletely understood if and how (chronic) airway inflammation affects vitamin D metabolism and action. We hypothesized that long-term exposure of primary bronchial epithelial cells (PBEC) to pro-inflammatory cytokines alters their vitamin D metabolism, antibacterial activity and expression of hCAP18/LL-37. To investigate this, PBEC were differentiated at the air-liquid interphase for 14 days in presence of the pro-inflammatory cytokines TNF-α and IL-1β (TNF-α/IL-1β), and subsequently exposed to vitamin D (inactive 25(OH)D3 and active 1,25(OH)2D3). Expression of hCAP18/LL-37, vitamin D receptor (VDR) and enzymes involved in vitamin D metabolism (CYP24A1 and CYP27B1) was determined using qPCR, Western blot and immunofluorescence staining. Furthermore, vitamin D-mediated antibacterial activity was assessed using non-typeable Haemophilus influenzae (NTHi). We found that TNF-α/IL-1β treatment reduced vitamin D-induced expression of hCAP18/LL-37 and killing of NTHi. In addition, CYP24A1 (a vitamin D-degrading enzyme) was increased by TNF-α/IL-1β, whereas CYP27B1 (that converts 25(OH)D3 to its active form) and VDR expression remained unaffected. Furthermore, we demonstrated that the TNF-α/IL-1β-mediated induction of CYP24A1 was at least in part mediated by the transcription factor specific protein 1 (Sp1) and the EGFR-MAPK-pathway. These findings indicate that TNF-α/IL-1β decreases vitamin D-mediated antibacterial activity and hCAP18/LL-37 expression via induction of CYP24A1, and suggests that chronic inflammation impairs protective responses induced by vitamin D.

  5. Inhibitory effects of Pycnogenol® (French maritime pine bark extract) on airway inflammation in ovalbumin-induced allergic asthma.

    Science.gov (United States)

    Shin, In-Sik; Shin, Na-Rae; Jeon, Chan-Mi; Hong, Ju-Mi; Kwon, Ok-Kyoung; Kim, Jong-Choon; Oh, Sei-Ryang; Hahn, Kyu-Woung; Ahn, Kyung-Seop

    2013-12-01

    Pycnogenol® (PYC) is a standardized extracts from the bark of the French maritime pine (Pinus maritime) and used as a herbal remedy for various diseases. In this study, we evaluated the effects of PYC on airway inflammation using a model of ovalbumin (OVA)-induced allergic asthma and RAW264.7 cells. PYC decreased nitric oxide production and reduced the interleukine (IL)-1β and IL-6 levels in LPS-stimulated RAW264.7 cells. PYC also reduced the expression of inducible nitric oxide synthase (iNOS) and matrix metalloproteinase (MMP)-9 and enhanced the expression of hemeoxygenase (HO)-1. In the in vivo experiment, PYC decreased the inflammatory cell count and the levels of IL-4, IL-5, IL-13, and immunoglobulin (Ig) E in BALF or serum. These results are consistent with the histological analysis findings, which showed that PYC attenuated the airway inflammation and mucus hypersecretion induced by OVA challenge. In addition, PYC enhanced the expression of HO-1. In contrast, PYC inhibited the elevated expression of iNOS and MMP-9 proteins induced by OVA challenge. In conclusion, PYC exhibits protective effects against OVA-induced asthma and LPS-stimulated RAW264.7 cells. These results suggest that PYC has potential as a therapeutic agent for the treatment of allergic asthma.

  6. Alternaria-Induced Release of IL-18 from Damaged Airway Epithelial Cells: n NF-kB Dependent Mechanism of Th2 Differentiation?

    OpenAIRE

    2012-01-01

    BACKGROUND: A series of epidemiologic studies have identified the fungus Alternaria as a major risk factor for asthma. The airway epithelium plays a critical role in the pathogenesis of allergic asthma. These reports suggest that activated airway epithelial cells can produce cytokines such as IL-25, TSLP and IL-33 that induce Th2 phenotype. However the epithelium-derived products that mediate the pro-asthma effects of Alternaria are not well characterized. We hypothesized that exposure of the...

  7. Myeloid differentiation factor 88-dependent signaling is critical for acute organic dust-induced airway inflammation in mice.

    Science.gov (United States)

    Bauer, Christopher; Kielian, Tammy; Wyatt, Todd A; Romberger, Debra J; West, William W; Gleason, Angela M; Poole, Jill A

    2013-06-01

    Organic dust exposure within agricultural environments results in airway diseases. Toll-like receptor 2 (TLR2) and TLR4 only partly account for the innate response to these complex dust exposures. To determine the central pathway in mediating complex organic dust-induced airway inflammation, this study targeted the common adaptor protein, myeloid differentiation factor 88 (MyD88), and investigated the relative contributions of receptors upstream from this adaptor. Wild-type, MyD88, TLR9, TLR4, IL-1 receptor I (RI), and IL-18R knockout (KO) mice were challenged intranasally with organic dust extract (ODE) or saline, according to an established protocol. Airway hyperresponsiveness (AHR) was assessed by invasive pulmonary measurements. Bronchoalveolar lavage fluid was collected to quantitate leukocyte influx and cytokine/chemokine (TNF-α, IL-6, chemokine [C-X-C motif] ligands [CXCL1 and CXCL2]) concentrations. Lung tissue was collected for histopathology. Lung cell apoptosis was determined by a terminal deoxynucleotidyl transferase dUTP nick-end labeling assay, and lymphocyte influx and intercellular adhesion molecule-1 (ICAM-1) expression were assessed by immunohistochemistry. ODE-induced AHR was significantly attenuated in MyD88 KO mice, and neutrophil influx and cytokine/chemokine production were nearly absent in MyD88 KO animals after ODE challenges. Despite a near-absent airspace inflammatory response, lung parenchymal inflammation was increased in MyD88 KO mice after repeated ODE exposures. ODE-induced epithelial-cell ICAM-1 expression was diminished in MyD88 KO mice. No difference was evident in the small degree of ODE-induced lung-cell apoptosis. Mice deficient in TLR9, TLR4, and IL-18R, but not IL-1IR, demonstrated partial protection against ODE-induced neutrophil influx and cytokine/chemokine production. Collectively, the acute organic dust-induced airway inflammatory response is highly dependent on MyD88 signaling, and is dictated, in part, by important

  8. Protective effects of the polyphenol sesamin on allergen-induced T(H2 responses and airway inflammation in mice.

    Directory of Open Access Journals (Sweden)

    Ching-Huei Lin

    Full Text Available Allergic asthma is a lifelong airway condition that affects people of all ages. In recent decades, asthma prevalence continues to increase globally, with an estimated number of 250,000 annual deaths attributed to the disease. Although inhaled corticosteroids and β-adrenergic receptor agonists are the primary therapeutic avenues that effectively reduce asthma symptoms, profound side effects may occur in patients with long-term treatments. Therefore, development of new therapeutic strategies is needed as alternative or supplement to current asthma treatments. Sesamin is a natural polyphenolic compound with strong anti-oxidative effects. Several studies have reported that sesamin is effective in preventing hypertension, thrombotic tendency, and neuroinflammation. However, it is still unknown whether sesamin can reduce asthma-induced allergic inflammation and airway hyperresponsiveness (AHR. Our study has revealed that sesamin exhibited significant anti-inflammatory effects in ovalbumin (OVA-induced murine asthma model. We found that treatments with sesamin after OVA sensitization and challenge significantly decreased expression levels of interleukin-4 (IL-4, IL-5, IL-13, and serum IgE. The numbers of total inflammatory cells and eosinophils in BALF were also reduced in the sesamin-treated animals. Histological results demonstrated that sesamin attenuated OVA-induced eosinophil infiltration, airway goblet cell hyperplasia, mucus occlusion, and MUC5AC expression in the lung tissue. Mice administered with sesamin showed limited increases in AHR compared with mice receiving vehicle after OVA challenge. OVA increased phosphorylation levels of IκB-α and nuclear expression levels of NF-κB, both of which were reversed by sesamin treatments. These data indicate that sesamin is effective in treating allergic asthma responses induced by OVA in mice.

  9. Protective effects of the polyphenol sesamin on allergen-induced T(H)2 responses and airway inflammation in mice.

    Science.gov (United States)

    Lin, Ching-Huei; Shen, Mei-Lin; Zhou, Ning; Lee, Chen-Chen; Kao, Shung-Te; Wu, Dong Chuan

    2014-01-01

    Allergic asthma is a lifelong airway condition that affects people of all ages. In recent decades, asthma prevalence continues to increase globally, with an estimated number of 250,000 annual deaths attributed to the disease. Although inhaled corticosteroids and β-adrenergic receptor agonists are the primary therapeutic avenues that effectively reduce asthma symptoms, profound side effects may occur in patients with long-term treatments. Therefore, development of new therapeutic strategies is needed as alternative or supplement to current asthma treatments. Sesamin is a natural polyphenolic compound with strong anti-oxidative effects. Several studies have reported that sesamin is effective in preventing hypertension, thrombotic tendency, and neuroinflammation. However, it is still unknown whether sesamin can reduce asthma-induced allergic inflammation and airway hyperresponsiveness (AHR). Our study has revealed that sesamin exhibited significant anti-inflammatory effects in ovalbumin (OVA)-induced murine asthma model. We found that treatments with sesamin after OVA sensitization and challenge significantly decreased expression levels of interleukin-4 (IL-4), IL-5, IL-13, and serum IgE. The numbers of total inflammatory cells and eosinophils in BALF were also reduced in the sesamin-treated animals. Histological results demonstrated that sesamin attenuated OVA-induced eosinophil infiltration, airway goblet cell hyperplasia, mucus occlusion, and MUC5AC expression in the lung tissue. Mice administered with sesamin showed limited increases in AHR compared with mice receiving vehicle after OVA challenge. OVA increased phosphorylation levels of IκB-α and nuclear expression levels of NF-κB, both of which were reversed by sesamin treatments. These data indicate that sesamin is effective in treating allergic asthma responses induced by OVA in mice.

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

    Science.gov (United States)

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

    2015-01-01

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

  11. Oxidative stress–induced mitochondrial dysfunction drives inflammation and airway smooth muscle remodeling in patients with chronic obstructive pulmonary disease

    Science.gov (United States)

    Wiegman, Coen H.; Michaeloudes, Charalambos; Haji, Gulammehdi; Narang, Priyanka; Clarke, Colin J.; Russell, Kirsty E.; Bao, Wuping; Pavlidis, Stelios; Barnes, Peter J.; Kanerva, Justin; Bittner, Anton; Rao, Navin; Murphy, Michael P.; Kirkham, Paul A.; Chung, Kian Fan; Adcock, Ian M.; Brightling, Christopher E.; Davies, Donna E.; Finch, Donna K.; Fisher, Andrew J.; Gaw, Alasdair; Knox, Alan J.; Mayer, Ruth J.; Polkey, Michael; Salmon, Michael; Singh, David

    2015-01-01

    Background Inflammation and oxidative stress play critical roles in patients with chronic obstructive pulmonary disease (COPD). Mitochondrial oxidative stress might be involved in driving the oxidative stress–induced pathology. Objective We sought to determine the effects of oxidative stress on mitochondrial function in the pathophysiology of airway inflammation in ozone-exposed mice and human airway smooth muscle (ASM) cells. Methods Mice were exposed to ozone, and lung inflammation, airway hyperresponsiveness (AHR), and mitochondrial function were determined. Human ASM cells were isolated from bronchial biopsy specimens from healthy subjects, smokers, and patients with COPD. Inflammation and mitochondrial function in mice and human ASM cells were measured with and without the presence of the mitochondria-targeted antioxidant MitoQ. Results Mice exposed to ozone, a source of oxidative stress, had lung inflammation and AHR associated with mitochondrial dysfunction and reflected by decreased mitochondrial membrane potential (ΔΨm), increased mitochondrial oxidative stress, and reduced mitochondrial complex I, III, and V expression. Reversal of mitochondrial dysfunction by the mitochondria-targeted antioxidant MitoQ reduced inflammation and AHR. ASM cells from patients with COPD have reduced ΔΨm, adenosine triphosphate content, complex expression, basal and maximum respiration levels, and respiratory reserve capacity compared with those from healthy control subjects, whereas mitochondrial reactive oxygen species (ROS) levels were increased. Healthy smokers were intermediate between healthy nonsmokers and patients with COPD. Hydrogen peroxide induced mitochondrial dysfunction in ASM cells from healthy subjects. MitoQ and Tiron inhibited TGF-β–induced ASM cell proliferation and CXCL8 release. Conclusions Mitochondrial dysfunction in patients with COPD is associated with excessive mitochondrial ROS levels, which contribute to enhanced inflammation and cell

  12. Amelioration of ovalbumin-induced allergic airway disease following Der p 1 peptide immunotherapy is not associated with induction of IL-35.

    Science.gov (United States)

    Moldaver, D M; Bharhani, M S; Wattie, J N; Ellis, R; Neighbour, H; Lloyd, C M; Inman, M D; Larché, M

    2014-03-01

    In the present study, we show therapeutic amelioration of established ovalbumin (OVA)-induced allergic airway disease following house dust mite (HDM) peptide therapy. Mice were sensitized and challenged with OVA and HDM protein extract (Dermatophagoides species) to induce dual allergen sensitization and allergic airway disease. Treatment of allergic mice with peptides derived from the major allergen Der p 1 suppressed OVA-induced airway hyperresponsiveness, tissue eosinophilia, and goblet cell hyperplasia upon rechallenge with allergen. Peptide treatment also suppressed OVA-specific T-cell proliferation. Resolution of airway pathophysiology was associated with a reduction in recruitment, proliferation, and effector function of T(H)2 cells and decreased interleukin (IL)-17⁺ T cells. Furthermore, peptide immunotherapy induced the regulatory cytokine IL-10 and increased the proportion of Fox p3⁺ cells among those expressing IL-10. Tolerance to OVA was not associated with increased IL-35. In conclusion, our results provide in vivo evidence for the creation of a tolerogenic environment following HDM peptide immunotherapy, leading to the therapeutic amelioration of established OVA-induced allergic airway disease.

  13. Human apolipoprotein E genotypes differentially modify house dust mite-induced airway disease in mice

    DEFF Research Database (Denmark)

    Yao, Xianglan; Dai, Cuilian; Fredriksson, Karin

    2012-01-01

    with reductions in lung mRNA levels of Th2 and Th17 cytokines, as well as chemokines (CCL7, CCL11, CCL24). huApoE4 mice had an intermediate phenotype, with attenuated AHR and IgE production, compared with muApoE mice, whereas airway inflammation and mucous cell metaplasia were not reduced. In contrast, HDM...

  14. Tiotropium attenuates IL-13-induced goblet cell metaplasia of human airway epithelial cells

    NARCIS (Netherlands)

    Kistemaker, Loes E. M.; Hiemstra, Pieter S.; Bos, I. Sophie T.; Bouwman, Susanne; van den Berge, Maarten; Hylkema, Machteld N.; Meurs, Herman; Kerstjens, Huib A. M.; Gosens, Reinoud

    2015-01-01

    BACKGROUND: It has been shown that acetylcholine is both a neurotransmitter and acts as a local mediator, produced by airway cells including epithelial cells. In vivo studies have demonstrated an indirect role for acetylcholine in epithelial cell differentiation. Here, we aimed to investigate direct

  15. Cigarette smoke-induced necroptosis and DAMP release trigger neutrophilic airway inflammation in mice

    NARCIS (Netherlands)

    Pouwels, Simon D; van der Toorn, Marco; Hesse, Laura; Gras, Renee; Ten Hacken, Nick H T; Krysko, Dmitri V; Vandenabeele, Peter; de Vries, Maaike; van Oosterhout, Antoon J M; Heijink, Irene H; Nawijn, Martijn C

    2015-01-01

    Recent data indicate a role for airway epithelial necroptosis, a regulated form of necrosis, and the associated release of damage associated molecular patterns (DAMPs) in the development of COPD. DAMPs can activate pattern recognition receptors (PRRs), triggering innate immune responses. We hypothes

  16. Connective tissue growth factor induces extracellular matrix in asthmatic airway smooth muscle

    NARCIS (Netherlands)

    Johnson, Peter R A; Burgess, Janette K; Ge, Qi; Poniris, Maree; Boustany, Sarah; Twigg, Stephen M; Black, Judith L

    2006-01-01

    Transforming growth factor (TGF)-beta and connective tissue growth factor may be implicated in extracellular matrix protein deposition in asthma. We have recently reported that TGF-beta increased connective tissue growth factor expression in airway smooth muscle cells isolated from patients with ast

  17. Rhinovirus infection induces extracellular matrix protein deposition in asthmatic and nonasthmatic airway smooth muscle cells

    NARCIS (Netherlands)

    Kuo, Curtis; Lim, Sam; King, Nicholas J C; Johnston, Sebastian L; Burgess, Janette K; Black, Judith L; Oliver, Brian G

    2011-01-01

    Airway remodeling, which includes increases in the extracellular matrix (ECM), is a characteristic feature of asthma and is correlated to disease severity. Rhinovirus (RV) infections are associated with increased risk of asthma development in young children and are the most common cause of asthma ex

  18. Chlamydophila pneumoniae induces a sustained airway hyperresponsiveness and inflammation in mice

    NARCIS (Netherlands)

    F. Blasi (Francesco); S. Aliberti (Stefano); L. Allegra (Luigi); G. Piatti (Gioia); P. Tarsia (Paolo); J.M. Ossewaarde (Jacobus); V. Verweij (Vivienne); F.P. Nijkamp (Frans); G. Folkerts (Gert)

    2007-01-01

    textabstractBackground: It has been reported that Chlamydophila (C.) pneumoniae is involved in the initiation and promotion of asthma and chronic obstructive pulmonary diseases (COPD). Surprisingly, the effect of C. pneumoniae on airway function has never been investigated.Methods: In this study, mi

  19. TCDD-Induced Activation of Aryl Hydrocarbon Receptor Inhibits Th17 Polarization and Regulates Non-Eosinophilic Airway Inflammation in Asthma.

    Directory of Open Access Journals (Sweden)

    Xiao-ming Li

    Full Text Available The aryl hydrocarbon receptor (AhR, a transcription factor of the bHLH/PAS family, has recently been demonstrated to regulate T cell differentiation. Whether AhR activation participates in allergic airway inflammation remains unknown. In the current study, using a non-eosinophilic asthma model, we demonstrate that 2, 3, 7, 8-tetrachlorodibenzo-P-dioxin (TCDD, a potent AhR ligand, reduced the airway infiltration of neutrophils, airway hyperresponsiveness and Th17 cytokine expression. Furthermore, stimulation with TCDD promoted Treg differentiation and inhibited Th17 differentiation. However, the maturation of dendritic cells may not be inhibited by AhR activation. This study thus indicates a critical role of TCDD-induced AhR activation in the regulation of non-eosinophilic airway inflammation.

  20. Justicia procumbens Extract (DW2008) Selectively Suppresses Th2 Cytokines in Splenocytes and Ameliorates Ovalbumin-Induced Airway Inflammation in a Mouse Model of Asthma.

    Science.gov (United States)

    Youm, Jihyun; Lee, Hyunyong; Chang, Hwan Bong; Jeon, Jihyun; Yoon, Mi Hee; Woo, Ji Young; Choi, Min-Soo; Hwang, Yunha; Seong, Seungkyoo; Na, Kyuheum; Yoon, Joobyoung

    2017-01-01

    DW2008 is an anhydrous ethanol extract of Justicia procumbens produced by Dong-Wha Pharmaceutical, Inc., Co. as a candidate anti-asthmatic drug. In this study, DW2008 selectively reduced T helper 2 (Th2) cytokines in mouse splenocytes and ameliorated ovalbumin-induced airway inflammation by downregulating pulmonary infiltration of differential inflammatory cells and Th2 cytokines more than a decoction or ethanol extract of J. procumbens did in a mouse asthma model. DW2008 also significantly inhibited airway hyperresponsiveness and reduced the thickness of the airway epithelium. HPLC analysis showed that the major peaks (justicidin A and B) of DW2008 were higher than those of the other extracts. Justicidin A and B significantly suppressed Th2 cytokine levels in mouse spleen cells and exhibited a protective effect in ovalbumin-induced airway inflammation. Our findings indicate that DW2008 effectively inhibits allergic airway inflammatory reactions and airway hyperresponsiveness in a mouse model of asthma, suggesting its potential as an anti-asthmatic agent.

  1. Deficiency of RAMP1 attenuates antigen-induced airway hyperresponsiveness in mice.

    Directory of Open Access Journals (Sweden)

    Manyu Li

    Full Text Available Asthma is a chronic inflammatory disease affecting the lung, characterized by breathing difficulty during an attack following exposure to an environmental trigger. Calcitonin gene-related peptide (CGRP is a neuropeptide that may have a pathological role in asthma. The CGRP receptor is comprised of two components, which include the G-protein coupled receptor, calcitonin receptor-like receptor (CLR, and receptor activity-modifying protein 1 (RAMP1. RAMPs, including RAMP1, mediate ligand specificity in addition to aiding in the localization of receptors to the cell surface. Since there has been some controversy regarding the effect of CGRP on asthma, we sought to determine the effect of CGRP signaling ablation in an animal model of asthma. Using gene-targeting techniques, we generated mice deficient for RAMP1 by excising exon 3. After determining that these mice are viable and overtly normal, we sensitized the animals to ovalbumin prior to assessing airway resistance and inflammation after methacholine challenge. We found that mice lacking RAMP1 had reduced airway resistance and inflammation compared to wildtype animals. Additionally, we found that a 50% reduction of CLR, the G-protein receptor component of the CGRP receptor, also ameliorated airway resistance and inflammation in this model of allergic asthma. Interestingly, the loss of CLR from the smooth muscle cells did not alter the airway resistance, indicating that CGRP does not act directly on the smooth muscle cells to drive airway hyperresponsiveness. Together, these data indicate that signaling through RAMP1 and CLR plays a role in mediating asthma pathology. Since RAMP1 and CLR interact to form a receptor for CGRP, our data indicate that aberrant CGRP signaling, perhaps on lung endothelial and inflammatory cells, contributes to asthma pathophysiology. Finally, since RAMP-receptor interfaces are pharmacologically tractable, it may be possible to develop compounds targeting the RAMP1/CLR

  2. Inhibition of airway epithelial-to-mesenchymal transition and fibrosis by kaempferol in endotoxin-induced epithelial cells and ovalbumin-sensitized mice.

    Science.gov (United States)

    Gong, Ju-Hyun; Cho, In-Hee; Shin, Daekeun; Han, Seon-Young; Park, Sin-Hye; Kang, Young-Hee

    2014-03-01

    Chronic airway remodeling is characterized by structural changes within the airway wall, including smooth muscle hypertrophy, submucosal fibrosis and epithelial shedding. Epithelial-to-mesenchymal transition (EMT) is a fundamental mechanism of organ fibrosis, which can be induced by TGF-β. In the in vitro study, we investigated whether 1-20 μM kaempferol inhibited lipopolysaccharide (LPS)-induced bronchial EMT in BEAS-2B cells. The in vivo study explored demoting effects of 10-20 mg/kg kaempferol on airway fibrosis in BALB/c mice sensitized with ovalbumin (OVA). LPS induced airway epithelial TGF-β1 signaling that promoted EMT with concurrent loss of E-cadherin and induction of α-smooth muscle actin (α-SMA). Nontoxic kaempferol significantly inhibited TGF-β-induced EMT process through reversing E-cadherin expression and retarding the induction of N-cadherin and α-SMA. Consistently, OVA inhalation resulted in a striking loss of epithelial morphology by displaying myofibroblast appearance, which led to bronchial fibrosis with submucosal accumulation of collagen fibers. Oral administration of kaempferol suppressed collagen deposition, epithelial excrescency and goblet hyperplasia observed in the lung of OVA-challenged mice. The specific inhibition of TGF-β entailed epithelial protease-activated receptor-1 (PAR-1) as with 20 μM kaempferol. The epithelial PAR-1 inhibition by SCH-79797 restored E-cadherin induction and deterred α-SMA induction, indicating that epithelial PAR-1 localization was responsible for resulting in airway EMT. These results demonstrate that dietary kaempferol alleviated fibrotic airway remodeling via bronchial EMT by modulating PAR1 activation. Therefore, kaempferol may be a potential therapeutic agent targeting asthmatic airway constriction.

  3. Extracellular acidification induces connective tissue growth factor production through proton-sensing receptor OGR1 in human airway smooth muscle cells

    Energy Technology Data Exchange (ETDEWEB)

    Matsuzaki, Shinichi [Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, Maebashi 371-8511 (Japan); Ishizuka, Tamotsu, E-mail: tamotsui@showa.gunma-u.ac.jp [Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, Maebashi 371-8511 (Japan); Yamada, Hidenori; Kamide, Yosuke; Hisada, Takeshi; Ichimonji, Isao; Aoki, Haruka; Yatomi, Masakiyo [Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, Maebashi 371-8511 (Japan); Komachi, Mayumi [Laboratory of Signal Transduction, Institute for Molecular and Cellular Regulation, Gunma University, Maebashi 371-8512 (Japan); Tsurumaki, Hiroaki; Ono, Akihiro; Koga, Yasuhiko [Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, Maebashi 371-8511 (Japan); Dobashi, Kunio [Gunma University Graduate School of Health Sciences, Maebashi 371-8511 (Japan); Mogi, Chihiro; Sato, Koichi; Tomura, Hideaki [Laboratory of Signal Transduction, Institute for Molecular and Cellular Regulation, Gunma University, Maebashi 371-8512 (Japan); Mori, Masatomo [Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, Maebashi 371-8511 (Japan); Okajima, Fumikazu [Laboratory of Signal Transduction, Institute for Molecular and Cellular Regulation, Gunma University, Maebashi 371-8512 (Japan)

    2011-10-07

    Highlights: {yields} The involvement of extracellular acidification in airway remodeling was investigated. {yields} Extracellular acidification alone induced CTGF production in human ASMCs. {yields} Extracellular acidification enhanced TGF-{beta}-induced CTGF production in human ASMCs. {yields} Proton-sensing receptor OGR1 was involved in acidic pH-stimulated CTGF production. {yields} OGR1 may play an important role in airway remodeling in asthma. -- Abstract: Asthma is characterized by airway inflammation, hyper-responsiveness and remodeling. Extracellular acidification is known to be associated with severe asthma; however, the role of extracellular acidification in airway remodeling remains elusive. In the present study, the effects of acidification on the expression of connective tissue growth factor (CTGF), a critical factor involved in the formation of extracellular matrix proteins and hence airway remodeling, were examined in human airway smooth muscle cells (ASMCs). Acidic pH alone induced a substantial production of CTGF, and enhanced transforming growth factor (TGF)-{beta}-induced CTGF mRNA and protein expression. The extracellular acidic pH-induced effects were inhibited by knockdown of a proton-sensing ovarian cancer G-protein-coupled receptor (OGR1) with its specific small interfering RNA and by addition of the G{sub q/11} protein-specific inhibitor, YM-254890, or the inositol-1,4,5-trisphosphate (IP{sub 3}) receptor antagonist, 2-APB. In conclusion, extracellular acidification induces CTGF production through the OGR1/G{sub q/11} protein and inositol-1,4,5-trisphosphate-induced Ca{sup 2+} mobilization in human ASMCs.

  4. Dust mite allergen, glutathione S-transferase, induces T cell immunoglobulin mucin domain-4 in dendritic cells to facilitate initiation of airway allergy.

    Science.gov (United States)

    Mo, L-H; Yang, L-T; Zeng, L; Xu, L-Z; Zhang, H-P; Li, L-J; Liu, J-Q; Xiao, X-J; Zheng, P-Y; Liu, Z-G; Yang, P-C

    2017-02-01

    Allergens from dust mites play a critical role in the pathogenesis of airway allergy. The mechanism by which dust mite allergens induce allergic diseases is not fully understood yet. This study tests a hypothesis that the eighth subtypes of Dermatophagoides farina allergen (Derf8) play an important role in the induction of airway allergy. The protein of Derf8 was synthesized via molecular cloning approach. Dendritic cells (DC) were stimulated with Derf8 in the culture, and then, the expression of T cell immunoglobulin mucin domain 4 (TIM4) in dendritic cells (DC) was analysed. The role of Derf8 in the induction of airway allergy was evaluated with a mouse model. Exposure to Derf8 markedly induced the TIM4 expression in DCs by modulating the chromatin at the TIM4 promoter locus. Derf8 played a critical role in the expansion of the T helper 2 response in the mouse airway via inducing DCs to produce TIM4. Administration with Derf8-depleted dust mite extracts (DME) inhibited the allergic inflammation and induced regulatory T cells in mice with airway allergy. Derf8 plays an important role in the initiation of dust mite allergy. Vaccination with Derf8-deficient DME is more efficient to inhibit the dust mite allergic inflammation than using wild DME. © 2016 John Wiley & Sons Ltd.

  5. An extract of Crataegus pinnatifida fruit attenuates airway inflammation by modulation of matrix metalloproteinase-9 in ovalbumin induced asthma.

    Directory of Open Access Journals (Sweden)

    In Sik Shin

    Full Text Available BACKGROUND: Crataegus pinnatifida (Chinese hawthorn has long been used as a herbal medicine in Asia and Europe. It has been used for the treatment of various cardiovascular diseases such as myocardial weakness, tachycardia, hypertension and arteriosclerosis. In this study, we investigated the anti-inflammatory effects of Crataegus pinnatifida ethanolic extracts (CPEE on Th2-type cytokines, eosinophil infiltration, expression of matrix metalloproteinase (MMP-9, and other factors, using an ovalbumin (OVA-induced murine asthma model. METHODS/PRINCIPAL FINDING: Airways of OVA-sensitized mice exposed to OVA challenge developed eosinophilia, mucus hypersecretion and increased cytokine levels. CPEE was applied 1 h prior to OVA challenge. Mice were administered CPEE orally at doses of 100 and 200 mg/kg once daily on days 18-23. Bronchoalveolar lavage fluid (BALF was collected 48 h after the final OVA challenge. Levels of interleukin (IL-4 and IL-5 in BALF were measured using enzyme-linked immunosorbent (ELISA assays. Lung tissue sections 4 µm in thickness were stained with Mayer's hematoxylin and eosin for assessment of cell infiltration and mucus production with PAS staining, in conjunction with ELISA, and Western blot analyses for the expression of MMP-9, intercellular adhesion molecule (ICAM-1 and vascular cell adhesion molecule (VCAM-1 protein expression. CPEE significantly decreased the Th2 cytokines including IL-4 and IL-5 levels, reduced the number of inflammatory cells in BALF and airway hyperresponsiveness, suppressed the infiltration of eosinophil-rich inflammatory cells and mucus hypersecretion and reduced the expression of ICAM-1, VCAM-1 and MMP-9 and the activity of MMP-9 in lung tissue of OVA-challenged mice. CONCLUSIONS: These results showed that CPEE can protect against allergic airway inflammation and can act as an MMP-9 modulator to induce a reduction in ICAM-1 and VCAM-1 expression. In conclusion, we strongly suggest the feasibility

  6. Anti-inflammatory effects of levalbuterol-induced 11β-hydroxysteroid dehydrogenase type 1 activity in airway epithelial cells

    Directory of Open Access Journals (Sweden)

    Matthew J Randall

    2015-01-01

    Full Text Available Airway epithelial NF-kB activation is observed in asthmatic subjects and is a cause of airway inflammation in mouse models of allergic asthma. Combination therapy with inhaled short-acting b2-agonists and corticosteroids significantly improves lung function and reduces inflammation in asthmatic subjects. Corticosteroids operate through a number of mechanisms to potently inhibit NF-kB activity. Since b-agonists can induce expression of 11b-HSD1, which converts inactive 11-keto corticosteroids into active 11-hydroxy corticosteroids, thereby potentiating the effects of endogenous glucocorticoids, we examined whether this mechanism is involved in the inhibition of NF-kB activation induced by the b-agonist albuterol in airway epithelial cells. Treatment of transformed murine Club cells (MTCC with (R-albuterol (levalbuterol, but not with (S- or a mixture of (R+S- (racemic albuterol, augmented mRNA expression of 11b-HSD1. MTCC were stably transfected with luciferase (luc reporter constructs under transcriptional regulation by NF-kB (NF-kB/luc or glucocorticoid response element (GRE/luc consensus motifs. Stimulation of NF-kB/luc MTCC with lipopolysaccharide (LPS or tumor necrosis factor-α (TNFα induced luciferase activity, which was inhibited by pretreatment with (R-, but not (S- or racemic albuterol. Furthermore, pretreatment of GRE/luc MTCC with (R-albuterol augmented 11-keto corticosteroid (cortisone induced luciferase activity, which was diminished by the 11β-HSD inhibitor glycyrrhetinic acid (18β-GA. LPS- and TNFα-induced NF-kB/luc activity was diminished in MTCC cells treated with a combination of cortisone and (R-albuterol, an effect that was inhibited by 18β-GA. Finally, pretreatment of MTCC cells with the combination of cortisone and (R-albuterol diminished LPS- and TNFα-induced pro-inflammatory cytokine production. These results demonstrate that levalbuterol augments conversion of inactive 11-keto corticosteroids into the active 11

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

    Directory of Open Access Journals (Sweden)

    Gustavo Nino

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

  8. Ozone-Induced Type 2 Immunity in Nasal Airways. Development and Lymphoid Cell Dependence in Mice.

    Science.gov (United States)

    Ong, Chee Bing; Kumagai, Kazuyoshi; Brooks, Phillip T; Brandenberger, Christina; Lewandowski, Ryan P; Jackson-Humbles, Daven N; Nault, Rance; Zacharewski, Timothy R; Wagner, James G; Harkema, Jack R

    2016-03-01

    Inhalation exposures to ozone commonly encountered in photochemical smog cause airway injury and inflammation. Elevated ambient ozone concentrations have been epidemiologically associated with nasal airway activation of neutrophils and eosinophils. In the present study, we elucidated the temporal onset and lymphoid cell dependency of eosinophilic rhinitis and associated epithelial changes in mice repeatedly exposed to ozone. Lymphoid cell-sufficient C57BL/6 mice were exposed to 0 or 0.5 parts per million (ppm) ozone for 1, 2, 4, or 9 consecutive weekdays (4 h/d). Lymphoid cell-deficient, Rag2(-/-)Il2rg(-/-) mice were similarly exposed for 9 weekdays. Nasal tissues were taken at 2 or 24 hours after exposure for morphometric and gene expression analyses. C57BL/6 mice exposed to ozone for 1 day had acute neutrophilic rhinitis, with airway epithelial necrosis and overexpression of mucosal Ccl2 (MCP-1), Ccl11 (eotaxin), Cxcl1 (KC), Cxcl2 (MIP-2), Hmox1, Il1b, Il5, Il6, Il13, and Tnf mRNA. In contrast, 9-day ozone exposure elicited type 2 immune responses in C57BL/6 mice, with mucosal mRNA overexpression of Arg1, Ccl8 (MCP-2), Ccl11, Chil4 (Ym2), Clca1 (Gob5), Il5, Il10, and Il13; increased density of mucosal eosinophils; and nasal epithelial remodeling (e.g., hyperplasia/hypertrophy, mucous cell metaplasia, hyalinosis, and increased YM1/YM2 proteins). Rag2(-/-)Il2rg(-/-) mice exposed to ozone for 9 days, however, had no nasal pathology or overexpression of transcripts related to type 2 immunity. These results provide a plausible paradigm for the activation of eosinophilic inflammation and type 2 immunity found in the nasal airways of nonatopic individuals subjected to episodic exposures to high ambient ozone.

  9. Comparison of Propofol and Desflurane Anesthesia Combined with Remifentanyl in Breast Surgery

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    Ertan Piri

    2014-03-01

    Full Text Available Aim: In this study, we aimed to compare the effects of propofol and desfluran anesthesia combined with remifentanil anesthesia on the various systems in short-term breast surgery. Material and Method: A prospective, randomized, controlled study design established for the short-term breast surgery planned, 40, ASA I- II patients aged 18-60 year-old. Group P (n=20 was named for the patients administered remifentanil and propofol and Group D (n=20 was named for the patients administered remifentanil and desflurane. For induction therapy, remifentanil of 1µg/kg dosage and Propofol of 2mg/kg dosage was adjusted for Group P and remifentanil of 1µg/kg dosage and % 3 end expiratory desflurane was adjusted for Group D. LMA applied for all of the patients. Maintenance treatment of remifentanil infusion with the dose of 0,25 µg/kg/min were used for both groups and Group P was also administered to 90 µg/kg/min infusion of Propofol. Tenoksikam with the dose of 20mg was used intravenously for all the patients 10min before the surgery finalized. Data of operation time, total anesthesia time, LMA extubation time, eye opening time, the time achievement of Aldrete score of 9 in postoperative period, VAS results and total remifentanil consumption were recorded. Blood samples were collected for ACTH and Cortizol levels 10min. before induction, 15 min after initial surgical incision and at 15th min of recovery period. Results: Hemodynamic stability maintained for both groups and no hemodynamic response occurred after surgical incisions. Wake-up time and recovery time were decreased in group D. We detected that ACTH and Cortizol levels were decreased in both groups although surgical stress was increased. Discussion: We suggest that desflurane-remifentanil drug combination can be used successfully as an alternative to TIVA for outpatient surgery.

  10. Desflurane reinforces the efficacy of propofol target-controlled infusion in patients undergoing laparoscopic cholecystectomy.

    Science.gov (United States)

    Chen, Po-Nien; Lu, I-Cheng; Chen, Hui-Ming; Cheng, Kuang-I; Tseng, Kuang-Yi; Lee, King-Teh

    2016-01-01

    Whether low-concentration desflurane reinforces propofol-based intravenous anesthesia on maintenance of anesthesia for patients undergoing laparoscopic cholecystectomy is to be determined. The aim of this study was to investigate whether propofol-based anesthesia adding low-concentration desflurane is feasible for laparoscopic cholecystectomy. Fifty-two patients undergoing laparoscopic cholecystectomy were enrolled in the prospective, randomized, clinical trial. Induction of anesthesia was achieved in all patients with fentanyl 2 μg/kg, lidocaine 1 mg/kg, propofol 2 mg/kg, and rocuronium 0.8 mg/kg to facilitate tracheal intubation and to initiate propofol target-controlled infusion (TCI) to effect site concentration (Ce: 4 μg/mL with infusion rate 400 mL/h). The patients were then allocated into either propofol TCI based (group P) or propofol TCI adding low-concentration desflurane (group PD) for maintenance of anesthesia. The peri-anesthesia hemodynamic responses to stimuli were measured. The perioperative psychomotor test included p-deletion test, minus calculation, orientation, and alert/sedation scales. Group PD showed stable hemodynamic responses at CO2 inflation, initial 15 minutes of operation, and recovery from general anesthesia as compared with group P. There is no significant difference between the groups in operation time and anesthesia time, perioperative psychomotor functional tests, postoperative vomiting, and pain score. Based on our findings, the anesthetic technique combination propofol and desflurane for the maintenance of general anesthesia for laparoscopic cholecystectomy provided more stable hemodynamic responses than propofol alone. The combined regimen is recommended for patients undergoing laparoscopic cholecystectomy.

  11. Desflurane increases intracranial pressure more and sevoflurane less than isoflurane in pigs subjected to intracranial hypertension.

    Science.gov (United States)

    Holmström, Anders; Akeson, J

    2004-04-01

    Desflurane and sevoflurane may have advantages over isoflurane in neuroanesthesia, but this is still under debate. A porcine model with experimental intracranial hypertension was used for paired comparison of desflurane, sevoflurane, and isoflurane with respect to the effects on cerebral blood flow (CBF), cerebrovascular resistance (CVR), and intracranial pressure (ICP). The agents, given in sequence to each of six pigs, were compared at 0.5 and 1.0 minimal alveolar concentrations (MAC) and three mean arterial blood pressure (MAP) levels (50, 70, and 90 mm Hg) at normocapnia and one MAP level (70 mm Hg) at hypocapnia. MAC for each agent had been previously determined in a standardized manner for comparison reliability. CBF was measured with Xe. MAP was lowered by inflation of a balloon catheter in the inferior caval vein and raised by inflation of a balloon catheter in the descending aorta. ICP was measured intraparenchymally. Two Fogarty catheters positioned extradurally were inflated to a baseline ICP of 20 to 22 mm Hg at 0.2 MAC of each agent. CBF and ICP with the three agents at normocapnia and MAP 70 and 90 mm Hg at both 0.5 and 1.0 MAC were as follows (P isoflurane > sevoflurane. None of the agents abolished CO2 reactivity. High-dose desflurane resulted in a higher CBF at hypocapnia than corresponding doses of sevoflurane or isoflurane, but there were no significant differences between the agents in ICP at hypocapnia. The present study showed that desflurane increased ICP more and sevoflurane less than isoflurane during normoventilation, but the differences disappeared with hyperventilation.

  12. Desflurane reinforces the efficacy of propofol target-controlled infusion in patients undergoing laparoscopic cholecystectomy

    Directory of Open Access Journals (Sweden)

    Po-Nien Chen

    2016-01-01

    Full Text Available Whether low-concentration desflurane reinforces propofol-based intravenous anesthesia on maintenance of anesthesia for patients undergoing laparoscopic cholecystectomy is to be determined. The aim of this study was to investigate whether propofol-based anesthesia adding low-concentration desflurane is feasible for laparoscopic cholecystectomy. Fifty-two patients undergoing laparoscopic cholecystectomy were enrolled in the prospective, randomized, clinical trial. Induction of anesthesia was achieved in all patients with fentanyl 2 μg/kg, lidocaine 1 mg/kg, propofol 2 mg/kg, and rocuronium 0.8 mg/kg to facilitate tracheal intubation and to initiate propofol target-controlled infusion (TCI to effect site concentration (Ce: 4 μg/mL with infusion rate 400 mL/h. The patients were then allocated into either propofol TCI based (group P or propofol TCI adding low-concentration desflurane (group PD for maintenance of anesthesia. The peri-anesthesia hemodynamic responses to stimuli were measured. The perioperative psychomotor test included p-deletion test, minus calculation, orientation, and alert/sedation scales. Group PD showed stable hemodynamic responses at CO2 inflation, initial 15 minutes of operation, and recovery from general anesthesia as compared with group P. There is no significant difference between the groups in operation time and anesthesia time, perioperative psychomotor functional tests, postoperative vomiting, and pain score. Based on our findings, the anesthetic technique combination propofol and desflurane for the maintenance of general anesthesia for laparoscopic cholecystectomy provided more stable hemodynamic responses than propofol alone. The combined regimen is recommended for patients undergoing laparoscopic cholecystectomy.

  13. Desflurane Allows for a Faster Emergence when Compared to Sevoflurane Without Affecting the Baseline Cognitive Recovery Time.

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    Joseph G. Werner

    2015-10-01

    Full Text Available Aims, We compared the effect of desflurane and sevoflurane on anesthesia recovery time in patients undergoing urological cystoscopic surgery. The Short Orientation Memory Concentration Test (SOMCT measured and compared cognitive impairment between groups and coughing was assessed throughout the anesthetic.Methods and Materials, This investigation included 75 ambulatory patients. Patients were randomized to receive either desflurane or sevoflurane. Inhalational anesthetics were discontinued after removal of the cystoscope and once repositioning of the patient was final. Coughing assessment and awakening time from anesthesia were assessed by a blinded observer.Statistical analysis used: Statistical analysis was performed by using t-test for parametric variables and Mann-Whitney U test for nonparametric variables. Results, The primary endpoint, mean time to eye-opening, was 5.0±2.5 minutes for desflurane, and 7.9±4.1 minutes for sevoflurane (p <0.001. There were no significant differences in time to SOMCT recovery (p=0.109, overall time spent in the post anesthesia care unit (p=0.924 or time to discharge (p=0.363. Median time until readiness for discharge was nine minutes in the desflurane group, while the sevoflurane group had a median time of 20 minutes (p=0.020. The overall incidence of coughing during the perioperative period was significantly higher in the desflurane (p=0.030. Conclusions, We re-confirmed that patients receiving desflurane had a faster emergence and met the criteria to be discharged from the post anesthesia care unit earlier. No difference was found in time to return to baseline cognition between desflurane and sevoflurane.

  14. Mycoplasma ovipneumoniae induces inflammatory response in sheep airway epithelial cells via a MyD88-dependent TLR signaling pathway.

    Science.gov (United States)

    Xue, Di; Ma, Yan; Li, Min; Li, Yanan; Luo, Haixia; Liu, Xiaoming; Wang, Yujiong

    2015-01-15

    Mycoplasma ovipneumoniae (M. ovipneumoniae) is a bacterium that specifically infects sheep and goat and causes ovine infectious pleuropneumonia. In an effort to understand the pathogen-host interaction between the M. ovipneumoniae and airway epithelial cells, we investigated the host inflammatory response using a primary air-liquid interface (ALI) epithelial culture model generated from bronchial epithelial cells of Ningxia Tan sheep (Ovis aries). The ALI culture of sheep bronchial epithelial cells showed a fully differentiated epithelium comprising distinct epithelial types, including the basal, ciliated and goblet cells. Exposure of ALI cultures to M. ovipneumoniae led to increased expression of Toll-like receptors (TLRs), and components of the myeloid differentiation factor 88 (MyD88)-dependent TLR signaling pathway, including the MyD88, TNF receptor-associated factor 6 (TRAF6), IL-1 receptor-associated kinases (IRAKs) and nuclear factor-kappa B (NF-κB), as well as subsequent pro-inflammatory cytokines in the epithelial cells. Of interest, infection with M. ovipneumoniae failed to induce the expression of TANK-binding kinase 1 (TBK1), TRAF3 and interferon regulatory factor 3 (IRF3), key components of the MyD88-independent signaling pathway. These results suggest that the MyD88-dependent TLR pathway may play a crucial role in sheep airway epithelial cells in response to M. ovipneumoniae infection, which also indicate that the ALI culture system may be a reliable model for investigating pathogen-host interactions between M. ovipneumoniae and airway epithelial cells.

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

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    Guoqing Wang

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

  16. Relaxation of soman-induced contracture of airway smooth muscle in vitro. (Reannouncement with new availability information)

    Energy Technology Data Exchange (ETDEWEB)

    Filbert, M.G.; Moore, D.H.; Adler, M.

    1992-12-31

    A possible role for beta-adrenergic agonists in the management of bronchoconstriction resulting from exposure to anticholinesterase compounds was investigated in vitro in canine tracheal smooth muscle. Norepinephrine, salbutamol and isoproterenol produced partial relaxation of soman-induced contractures. However, the relaxation induced was not sustained; muscle tensions returned to pretreatment levels within minutes despite the continued presence of beta-agonists. Increasing cAMP levels with the non beta-agonist bronchodilators such as thoophylline, a phosphodiesterase inhibitor, or forskolin, a specific stimulator of adenylate cyclase, resulted in more complete and longer lasting relaxation, suggesting that beta-adrenoceptor desensitization may contribute to the failure by beta-agonists to produce sustained relaxation. Nerve agents, Soman, Toxicity, Airway smooth muscle, In vitro, Physiology, Effects.

  17. Nasal administration of interleukin-33 induces airways angiogenesis and expression of multiple angiogenic factors in a murine asthma surrogate.

    Science.gov (United States)

    Shan, Shan; Li, Yan; Wang, Jingjing; Lv, Zhe; Yi, Dawei; Huang, Qiong; Corrigan, Chris J; Wang, Wei; Quangeng, Zhang; Ying, Sun

    2016-05-01

    The T-helper cell type 2-promoting cytokine interleukin-33 (IL-33) has been implicated in asthma pathogenesis. Angiogenesis is a feature of airways remodelling in asthma. We hypothesized that IL-33 induces airways angiogenesis and expression of angiogenic factors in an established murine surrogate of asthma. In the present study, BALB/c mice were subjected to serial intranasal challenge with IL-33 alone for up to 70 days. In parallel, ovalbumin (OVA) -sensitized mice were subjected to serial intranasal challenge with OVA or normal saline to serve as positive and negative controls, respectively. Immunohistochemical analysis of expression of von Willebrand factor and erythroblast transformation-specific-related gene, both blood vessel markers, and angiogenic factors angiogenin, insulin-like growth factor-1, endothelin-1, epidermal growth factor and amphiregulin was performed in lung sections ex vivo. An established in-house assay was used to test whether IL-33 was able to induce microvessel formation by human vascular endothelial cells. Results showed that serial intranasal challenge of mice with IL-33 or OVA resulted in proliferation of peribronchial von Willebrand factor-positive blood vessels to a degree closely related to the total expression of the angiogenic factors amphiregulin, angiogenin, endothelin-1, epidermal growth factor and insulin-like growth factor-1. IL-33 also induced microvessel formation by human endothelial cells in a concentration-dependent fashion in vitro. Our data are consistent with the hypothesis that IL-33 has the capacity to induce angiogenesis at least partly by increasing local expression of multiple angiogenic factors in an allergen-independent murine asthma surrogate, and consequently that IL-33 or its receptor is a potential novel molecular target for asthma therapy.

  18. Inhibition of allergic airway inflammation by antisense-induced blockade of STAT6 expression

    Institute of Scientific and Technical Information of China (English)

    TIAN Xin-rui; TIAN Xin-li; BO Jian-ping; LI Shao-gang; LIU Zhuo-la; NIU Bo

    2011-01-01

    Background The signal transducer and activator of transcription 6 (STAT6) expression in lung epithelial cells plays a pivotal role in asthma pathogenesis. Activation of STAT6 expression results in T helper cell type 2 (Th2) cell differentiation leading to Th2-mediated IgE production, development of allergic airway inflammation and hyperreactivity. Therefore,antagonizing the expression and/or the function of STAT6 could be used as a mode of therapy for allergic airway inflammation.Methods In this study, we synthesized a 20-mer phosphorothioate antisense oligonucleotide (ASODN) overlapping the translation starting site of STAT6 and constructed STAT6 antisense RNA (pANTI-STAT6), then transfected them into murine spleen lymphocytes and analyzed the effects of antagonizing STAT6 function in vitro and in a murine model of asthma.Results In vitro, we showed suppression of STAT6 expression and interleukin (IL)-4 production of lymphocytes by STAT6 ASODN. This effect was more prominent when cells were cultured with pANTI-STAT6. In a murine model of asthma associated with allergic pulmonary inflammation in ovalbumin (OVA)-sensitized mice, local intranasal administration of fluorescein isothiocyanate (FITC)-labeled STAT6 ASODN to DNA uptake in lung cells was accompanied by a reduction of intracellular STAT6 expression. Such intrapulmonary blockade of STAT6 expression abrogated signs of lung inflammation, infiltration of eosinophils and Th2 cytokine production.Conclusion These data suggest a critical role of STAT6 in the pathogenesis of asthma and the use of local delivery of STAT6 ASODN as a novel approach for the treatment of allergic airway inflammation such as in asthma.

  19. Airway hyperresponsiveness induced by repeated esophageal infusion of HCl in guinea pigs.

    Science.gov (United States)

    Cheng, Yan-Mei; Cao, Ai-Li; Zheng, Jian-Pu; Wang, Hong-Wei; Sun, Yong-Shun; Liu, Chun-Fang; Zhang, Bei-Bei; Wang, Yi; Zhu, Sheng-Liang; Wu, Da-Zheng

    2014-11-01

    Gastroesophageal reflux is a common disorder closely related to chronic airway diseases, such as chronic cough, asthma, chronic bronchitis, and chronic obstructive disease. Indeed, gastroesophageal acid reflux into the respiratory tract causes bronchoconstriction, but the underlying mechanisms have still not been clarified. This study aimed to elucidate functional changes of bronchial smooth muscles (BSMs) isolated from guinea pigs in an animal model of gastroesophageal reflux. The marked airway inflammation, hyperresponsiveness and remodeling were observed after guinea pigs were exposed to intraesophageal HCl infusion for 14 days. In addition, contractile responses to acetylcholine (ACh), KCl, electrical field stimulation, and extracellular Ca(2+) were greater in guinea pigs infused with HCl compared with control groups. The L-type voltage-dependent Ca(2+) channels (L-VDCC) blocker, nicardipine, significantly inhibited ACh- and Ca(2+)-enhanced BSM contractions in guinea pigs infused with HCl. The Rho-kinase inhibitor, Y27632, attenuated ACh-enhanced BSM contractions in guinea pigs infused with HCl. Moreover, mRNA and protein expressions for muscarinic M2 and M3 receptors, RhoA, and L-VDCC in BSM were detected by real-time PCR and Western blot. Expressions of mRNA and protein for muscarinic M3 receptors, RhoA, and L-VDCC were greater than in BSM of HCl-infused guinea pigs, whereas levels of muscarinic M2 receptors were unchanged. We demonstrate that acid infusion to the lower esophagus and, subsequently, microaspiration into the respiratory tract in guinea pigs leads to airway hyperresponsiveness and overactive BSM. Functional and molecular results indicate that overactive BSM is the reason for enhancement of extracellular Ca(2+) influx via L-VDCC and Ca(2+) sensitization through Rho-kinase signaling.

  20. Old method, new drugs: comparison of the efficacy of sevoflurane, isoflurane, and desflurane in achieving controlled hypotension in spinal surgery.

    Science.gov (United States)

    Kurt, Filiz; Derbent, Abdurrahim; Demirag, Kubilay; Eris, Oguz; Uyar, Mehmet; Islekel, Sertac

    2005-01-01

    This study compared the efficacy of isoflurane, sevoflurane, and desflurane in achieving hemodynamic stability in spinal procedures using moderate levels of controlled hypotension. After obtaining ethics committee approval and written informed consent, 32 American Surgical Association I-II patients were randomly allocated to receive isoflurane (n=12), sevoflurane (n=10), or desflurane (n=10) in O2-N2O (1:1) for maintenance of anesthesia. The induction of anesthesia, fentanyl dosage, and initial and maintenance volume replacements were standardized. Blood pressure was invasively monitored and maintained within a target systolic blood pressure (SBP) range of 80 to 90 mm Hg during the study. SBP outside this range was recorded. Volatile anesthetic concentration was adjusted according to the same protocol for all 3 agents. SPB control was maintained better with sevoflurane and isoflurane than desflurane; median SBP was outside the target range during 32% (range, 15%-55%) of study time with isoflurane, 26% (12%-42%) with sevoflurane, and 44% (20%-80%) with desflurane. Total blood loss did not differ among the groups. Sevoflurane and isoflurane administered in 2 L/min fresh gas flow were more effective than desflurane in achieving controlled hypotension in spinal surgery.

  1. Effect of unilateral vagus blockade on antigen-induced airway obstruction.

    Science.gov (United States)

    Zimmermann, I; Islam, M S; Ulmer, W T

    1976-01-01

    Respiratory hypersensitivity and the effect of unilateral vagus blockade on the same, after the use of Ascaris extract aerosol, are studied in three boxer dogs with spontaneous reactivity to this aerosol. The dogs were exposed initially to Ascaris extract aerosol, and this exposure was repeated after unilateral vagus blockade and after its lavage. The principal parameters, deltaPoes (mm Hg)/100 ml TV, are given as a measurement of airway flow resistance and respiratory rates. The spontaneous respiratory distress observed in all the animals after exposure to the mentioned aerosol was avoided with unilateral blockade of the nervus vagus.

  2. Active components of ginger potentiate β-agonist-induced relaxation of airway smooth muscle by modulating cytoskeletal regulatory proteins.

    Science.gov (United States)

    Townsend, Elizabeth A; Zhang, Yi; Xu, Carrie; Wakita, Ryo; Emala, Charles W

    2014-01-01

    β-Agonists are the first-line therapy to alleviate asthma symptoms by acutely relaxing the airway. Purified components of ginger relax airway smooth muscle (ASM), but the mechanisms are unclear. By elucidating these mechanisms, we can explore the use of phytotherapeutics in combination with traditional asthma therapies. The objectives of this study were to: (1) determine if 6-gingerol, 8-gingerol, or 6-shogaol potentiate β-agonist-induced ASM relaxation; and (2) define the mechanism(s) of action responsible for this potentiation. Human ASM was contracted in organ baths. Tissues were relaxed dose dependently with β-agonist, isoproterenol, in the presence of vehicle, 6-gingerol, 8-gingerol, or 6-shogaol (100 μM). Primary human ASM cells were used for cellular experiments. Purified phosphodiesterase (PDE) 4D or phospholipase C β enzyme was used to assess inhibitory activity of ginger components using fluorescent assays. A G-LISA assay was used to determine the effects of ginger constituents on Ras homolog gene family member A activation. Significant potentiation of isoproterenol-induced relaxation was observed with each of the ginger constituents. 6-Shogaol showed the largest shift in isoproterenol half-maximal effective concentration. 6-Gingerol, 8-gingerol, or 6-shogaol significantly inhibited PDE4D, whereas 8-gingerol and 6-shogaol also inhibited phospholipase C β activity. 6-Shogaol alone inhibited Ras homolog gene family member A activation. In human ASM cells, these constituents decreased phosphorylation of 17-kD protein kinase C-potentiated inhibitory protein of type 1 protein phosphatase and 8-gingerol decreased myosin light chain phosphorylation. Isolated components of ginger potentiate β-agonist-induced relaxation in human ASM. This potentiation involves PDE4D inhibition and cytoskeletal regulatory proteins. Together with β-agonists, 6-gingerol, 8-gingerol, or 6-shogaol may augment existing asthma therapy, resulting in relief of symptoms through

  3. A low dose of droperidol decreases the desflurane concentration needed during breast cancer surgery: a randomized double-blinded study

    Science.gov (United States)

    Adachi, Yushi U; Makita, Koshi

    2017-01-01

    Background Droperidol (DHB) reportedly reduces the dose of propofol needed to achieve hypnosis when anesthesia is induced and decreases the bispectral index (BIS) in propofol-sedated patients during spinal anesthesia. We reported previously that supplemental DHB decreased the BIS after the administration of sevoflurane and remifentanil. This study investigated the effect of DHB on desflurane (DES) consumption in a clinical setting. Methods We conducted a prospective, randomized double-blinded study of 35 women with American Society of Anesthesiologist physical status I or II who underwent a mastectomy. Either DHB (20 µg/kg) or a saline placebo was administered to patients 30 min after the induction of anesthesia. A blinded anesthesiologist maintained a BIS value of 50 during anesthesia by modulating inhaled DES concentrations that changed 0.5% at 2.5 min intervals and maintained analgesia via the constant administration of remifentanil by referring to vital signs. The primary endpoint was the effect of DHB on DES consumption. The secondary endpoints included blood circulatory parameters, the time from the end of surgery to extubation, and discharge time between the groups. Results The characteristics of the patients did not differ between the groups. The DHB group used a mean of 27.2 ± 6.0 ml of DES compared with 41.4 ± 9.5 ml by the placebo group (P effects.

  4. Isoquercitrin from Argemone platyceras inhibits carbachol and leukotriene D4-induced contraction in guinea-pig airways.

    Science.gov (United States)

    Fernandez, Jacquelina; Reyes, Ricardo; Ponce, Hector; Oropeza, Martha; Vancalsteren, Marie-Rose; Jankowski, Christopher; Campos, Maria G

    2005-10-17

    Argemone platyceras is used in Mexico as a remedy for cough, bronchitis and pneumonia. The present study was performed to investigate the pharmacological anti-asthmatic properties of Argemone platyceras on airways and to identify its active principles. Methanol extracts of leaves and flowers, subsequent organic and aqueous extraction phases, and silica gel chromatography fractions were assayed on the carbachol-induced response, and/or on ovalbumin antigenic challenge, and on leukotriene D(4)-induced response of tracheae from sensitized and non-sensitized guinea-pigs. Methanol extracts, ethyl-acetate phase, and its fractions 6 and 7 inhibited the carbachol-induced contractile response. Isoquercitrin and rutin were the main compounds found in fractions 6 and 7 respectively. Isoquercitrin (fraction 6) abolished the response to ovalbumin, and decreased the contractile response to leukotriene D(4). Because of its effect on carbachol-induced contractile response, on the late-phase response to ovalbumin, and on leukotriene D(4)-induced contractile response, isoquercitrin might be highly useful in treatment of asthma.

  5. O3-induced airway hyperresponsiveness to noncholinergic system and other stimuli

    Energy Technology Data Exchange (ETDEWEB)

    Campos, M.G.; Segura, P.; Vargas, M.H.; Vanda, B.; Ponce-Monter, H.; Selman, M.; Montano, L.M. (Departamento de Fisiologia y Farmacologia, Facultad de Medicina Veterinaria y Zootecnia, Universidad Nacional Autonoma de Mexico, DF (Mexico))

    1992-07-01

    The effect of O3 exposure (3 ppm, 1 h) on the in vivo and in vitro airway responsiveness, as well as the changes in cell contents in bronchoalveolar lavage (BAL) fluid, were evaluated 16-18 h after O3 exposure in sensitized and nonsensitized male guinea pigs. The sensitization procedure was performed through repeated inhalation of ovalbumin for 3 wk. Increase in pulmonary insufflation pressure produced by the excitatory nonadrenergic noncholinergic (eNANC) system, histamine, and antigen were assessed in in vivo conditions, whereas airway responsiveness to histamine and substance P was evaluated in in vitro conditions by use of tracheal chains with or without epithelium and lung parenchymal strips. The authors found that O3 exposure (1) increased the neutrophil content in BAL fluids in both sensitized and nonsensitized guinea pigs, (2) caused hyperresponsiveness to eNANC stimulation in nonsensitized guinea pigs (although combination of sensitization and O3 exposure paradoxically abolished the hyperresponsiveness to eNANC stimulation), (3) increased the in vivo bronchoconstrictor responses to histamine and antigen, (4) caused hyperresponsiveness to substance P in nonsensitized tracheae with or without epithelium and in sensitized tracheae with epithelium, (5) did not modify the responsiveness to histamine in tracheae with or without epithelium (and in addition, epithelium removal caused hyperresponsiveness to histamine even in those tracheae exposed to O3), and (6) produced hyperresponsiveness to histamine in lung parenchymal strips either from sensitized or nonsensitized guinea pigs.

  6. Deficiency of nitric oxide in allergen-induced airway hyperreactivity to contractile agonists after the early asthmatic reaction : An ex vivo study

    NARCIS (Netherlands)

    deBoer, J; Meurs, H; Coers, W; Koopal, M; Bottone, AE; Visser, AC; Timens, W; Zaagsma, J

    1996-01-01

    1 Using a guinea-pig model of allergic asthma, we investigated the role of nitric oxide (NO) in allergen-induced airway hyperreactivity after the early asthmatic reaction, by examining the effects of the NO-synthase inhibitor N-omega-nitro-L-arginine methyl ester (L-NAME) on the responsiveness to me

  7. Role of L-arginine in the deficiency of nitric oxide and airway hyperreactivity after the allergen-induced early asthmatic reaction in guinea-pigs

    NARCIS (Netherlands)

    de Boer, J; Duyvendak, M; Schuurman, F.E; Pouw, F.M W; Zaagsma, Hans; Meurs, Herman

    1999-01-01

    1 Using a guinea-pig model of allergic asthma, we investigated the role of L-arginine limitation in the allergen-induced deficiency of nitric oxide (NO) and airway hyperreactivity (AHR) after the early asthmatic reaction, by examining the effects of various concentrations of the NO synthase (NOS) su

  8. Differential Roles of Hydrogen Peroxide in Adaptive and Inflammatory Gene Expression Induced by Exposure of Human Airway Epithelial Cells to Zn2+

    Science.gov (United States)

    Oxidant stress is believed to play an important role in particulate matter (PM)–mediated toxicity in the respiratory tract. Zinc (Zn2+) is a ubiquitous component of PM that has been shown to induce adverse responses such as inflammatory and adaptive gene expression in airway epit...

  9. Elastase-Induced Parenchymal Disruption and Airway Hyper Responsiveness in Mouse Precision Cut Lung Slices: Toward an Ex vivo COPD Model

    Science.gov (United States)

    Van Dijk, Eline M.; Culha, Sule; Menzen, Mark H.; Bidan, Cécile M.; Gosens, Reinoud

    2017-01-01

    Background: COPD is a progressive lung disease characterized by emphysema and enhanced bronchoconstriction. Current treatments focused on bronchodilation can delay disease progression to some extent, but recovery or normalization of loss of lung function is impossible. Therefore, novel therapeutic targets are needed. The importance of the parenchyma in airway narrowing is increasingly recognized. In COPD, the parenchyma and extracellular matrix are altered, possibly affecting airway mechanics and enhancing bronchoconstriction. Our aim was to set up a comprehensive ex vivo Precision Cut Lung Slice (PCLS) model with a pathophysiology resembling that of COPD and integrate multiple readouts in order to study the relationship between parenchyma, airway functionality, and lung repair processes. Methods: Lungs of C57Bl/6J mice were sliced and treated ex vivo with elastase (2.5 μg/ml) or H2O2 (200 μM) for 16 h. Following treatment, parenchymal structure, airway narrowing, and gene expression levels of alveolar Type I and II cell repair were assessed. Results: Following elastase, but not H2O2 treatment, slices showed a significant increase in mean linear intercept (Lmi), reflective of emphysema. Only elastase-treated slices showed disorganization of elastin and collagen fibers. In addition, elastase treatment lowered both alveolar Type I and II marker expression, whereas H2O2 stimulation lowered alveolar Type I marker expression only. Furthermore, elastase-treated slices showed enhanced methacholine-induced airway narrowing as reflected by increased pEC50 (5.87 at basal vs. 6.50 after elastase treatment) and Emax values (47.96 vs. 67.30%), and impaired chloroquine-induced airway opening. The increase in pEC50 correlated with an increase in mean Lmi. Conclusion: Using this model, we show that structural disruption of elastin fibers leads to impaired alveolar repair, disruption of the parenchymal compartment, and altered airway biomechanics, enhancing airway contraction

  10. Dietary Fiber Intake Regulates Intestinal Microflora and Inhibits Ovalbumin-Induced Allergic Airway Inflammation in a Mouse Model.

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    Zhang, Zhiyu; Shi, Lei; Pang, Wenhui; Liu, Wenwen; Li, Jianfeng; Wang, Haibo; Shi, Guanggang

    2016-01-01

    Recently, academic studies suggest that global growth of airway allergic disease has a close association with dietary changes including reduced consumption of fiber. Therefore, appropriate dietary fiber supplementation might be potential to prevent airway allergic disease (AAD). We investigated whether dietary fiber intake suppressed the induction of AAD and tried to elucidate the possible underlying mechanisms. The control mice and AAD model mice fed with 4% standard-fiber chow, while low-fiber group of mice fed with a 1.75% low-fiber chow. The two fiber-intervened groups including mice, apart from a standard-fiber diet, were also intragastric (i.g.) administrated daily with poorly fermentable cellulose or readily fermentable pectin (0.4% of daily body weight), respectively. All animals except normal mice were sensitized and challenged with ovalbumin (OVA) to induce airway allergic inflammation. Hallmarks of AAD were examined by histological analysis and ELISA. The variation in intestinal bacterial composition was assessed by qualitative analysis of 16S ribosomal DNA (rDNA) content in fecal samples using real-time PCR. Low-fiber diet aggravated inflammatory response in ovalbumin-induced allergic mice, whereas dietary fiber intake significantly suppressed the allergic responses, attenuated allergic symptoms of nasal rubbing and sneezing, decreased the pathology of eosinophil infiltration and goblet cell metaplasia in the nasal mucosa and lung, inhibited serum OVA-specific IgE levels, and lowered the levels of Th2 cytokines in NALF and BALF, but, increased Th1 (IFN-γ) cytokines. Additionally, dietary fiber intake also increased the proportion of Bacteroidetes and Actinobacteria, and decreased Firmicutes and Proteobacteria. Levels of probiotic bacteria, such as Lactobacillus and Bifidobacterium, were upgraded significantly. Long-term deficiency of dietary fiber intake increases the susceptibility to AAD, whereas proper fiber supplementation promotes effectively the

  11. Dietary Fiber Intake Regulates Intestinal Microflora and Inhibits Ovalbumin-Induced Allergic Airway Inflammation in a Mouse Model.

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    Zhiyu Zhang

    Full Text Available Recently, academic studies suggest that global growth of airway allergic disease has a close association with dietary changes including reduced consumption of fiber. Therefore, appropriate dietary fiber supplementation might be potential to prevent airway allergic disease (AAD.We investigated whether dietary fiber intake suppressed the induction of AAD and tried to elucidate the possible underlying mechanisms.The control mice and AAD model mice fed with 4% standard-fiber chow, while low-fiber group of mice fed with a 1.75% low-fiber chow. The two fiber-intervened groups including mice, apart from a standard-fiber diet, were also intragastric (i.g. administrated daily with poorly fermentable cellulose or readily fermentable pectin (0.4% of daily body weight, respectively. All animals except normal mice were sensitized and challenged with ovalbumin (OVA to induce airway allergic inflammation. Hallmarks of AAD were examined by histological analysis and ELISA. The variation in intestinal bacterial composition was assessed by qualitative analysis of 16S ribosomal DNA (rDNA content in fecal samples using real-time PCR.Low-fiber diet aggravated inflammatory response in ovalbumin-induced allergic mice, whereas dietary fiber intake significantly suppressed the allergic responses, attenuated allergic symptoms of nasal rubbing and sneezing, decreased the pathology of eosinophil infiltration and goblet cell metaplasia in the nasal mucosa and lung, inhibited serum OVA-specific IgE levels, and lowered the levels of Th2 cytokines in NALF and BALF, but, increased Th1 (IFN-γ cytokines. Additionally, dietary fiber intake also increased the proportion of Bacteroidetes and Actinobacteria, and decreased Firmicutes and Proteobacteria. Levels of probiotic bacteria, such as Lactobacillus and Bifidobacterium, were upgraded significantly.Long-term deficiency of dietary fiber intake increases the susceptibility to AAD, whereas proper fiber supplementation promotes

  12. Protective effect of high-dose montelukast on salbutamol-induced homologous desensitisation in airway smooth muscle.

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    Fogli, Stefano; Stefanelli, Fabio; Martelli, Alma; Daniele, Simona; Testai, Lara; Calderone, Vincenzo; Trincavelli, Maria Letizia; Martini, Claudia; Breschi, Maria Cristina

    2013-12-01

    Montelukast (MK) is a potent cysteinyl-leukotriene receptor antagonist that causes dose-related improvements in chronic asthma. We sought to determine whether MK was able to prevent salbutamol-induced tolerance in airway smooth muscle. Homologous β2-adrenoceptor desensitisation models were established in guinea-pigs and in human bronchial smooth muscle cells (BSMC) by chronic salbutamol administration. Characterisation tools included measurement of the response of tracheal smooth muscle tissues to salbutamol, analysis of gene expression and receptor trafficking, evaluation of intracellular cAMP levels and phosphodiesterase (PDE) activity in human bronchial smooth muscle cells. Salbutamol-induced β2-adrenoceptor desensitisation was characterised by β2-agonist hyporesponsiveness (-30%, p salbutamol. Prolonged salbutamol treatment significantly decreased cAMP synthesis, induced a complete removal of the β2-adrenoceptor from plasma membrane with a parallel increase in the cytosol and increased PDE4D5 gene transcription and PDE activity in human bronchial smooth muscle cells. In homologously desensitised BSMC, MK 30 μM for 24 h was able to prevent salbutamol subsensitivity and such an effect was associated with inhibition of salbutamol-induced PDE4 activity and restoration of membrane β2-adrenoceptor expression and function. These findings suggest the presence of a favourable interaction between MK and β2-adrenoceptor agonists that might improve the therapeutic index of bronchodilators in patients with chronic respiratory diseases.

  13. Antigen-induced airway obstruction and the influence of vagus blockade.

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    Zimmermann, I; Islam, M S; Lanser, K; Ulmer, W T

    1976-01-01

    Respiratory hypersensitivity to Ascaris antigens is carried out on 9 dogs. The participation of vagus reflex on this respiratory distress is studied in 4 of these dogs. The dogs were exposed initially to Ascaris aerosol, then to egg albumin and NaCl aerosol for control, and once more to Ascaris aerosol after bilateral vagi blockade and lavage, respectively. The principal parameters studied were deltaPoes (mm Hg)/100 ml TV as a measurement of flow resistance in the airways, and respiratory rates (Poes=changes of oesphagus pressure; TV=tidal volume). All the animals presented a significant respiratory distress with Ascaris aerosol, which could be clearly avoided with the central bilateral blockade of nervus vagus.

  14. Effect of a single dose of esmolol on the bispectral index to endotracheal intubation during desflurane anesthesia

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    Choi, Eun Mi; Min, Kyeong Tae; Lee, Jeong Rim; Lee, Tai Kyung; Choi, Seung Ho

    2013-01-01

    Background In this prospective, randomized, double-blind, placebo-controlled trial, we investigated the effect of a single dose of esmolol on the bispectral index (BIS) to endotracheal intubation during desflurane anesthesia. Methods After induction of anesthesia, 60 patients were mask-ventilated with desflurane (end-tidal 1 minimum alveolar concentration) for 5 min and then received either normal saline, esmolol 0.5 or 1 mg/kg, 1 min prior to intubation (control, esmolol-0.5 and esmolol-1 gr...

  15. PKA and Epac cooperate to augment bradykinin-induced interleukin-8 release from human airway smooth muscle cells

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    Halayko Andrew J

    2009-09-01

    Full Text Available Abstract Background Airway smooth muscle contributes to the pathogenesis of pulmonary diseases by secreting inflammatory mediators such as interleukin-8 (IL-8. IL-8 production is in part regulated via activation of Gq-and Gs-coupled receptors. Here we study the role of the cyclic AMP (cAMP effectors protein kinase A (PKA and exchange proteins directly activated by cAMP (Epac1 and Epac2 in the bradykinin-induced IL-8 release from a human airway smooth muscle cell line and the underlying molecular mechanisms of this response. Methods IL-8 release was assessed via ELISA under basal condition and after stimulation with bradykinin alone or in combination with fenoterol, the Epac activators 8-pCPT-2'-O-Me-cAMP and Sp-8-pCPT-2'-O-Me-cAMPS, the PKA activator 6-Bnz-cAMP and the cGMP analog 8-pCPT-2'-O-Me-cGMP. Where indicated, cells were pre-incubated with the pharmacological inhibitors Clostridium difficile toxin B-1470 (GTPases, U0126 (extracellular signal-regulated kinases ERK1/2 and Rp-8-CPT-cAMPS (PKA. The specificity of the cyclic nucleotide analogs was confirmed by measuring phosphorylation of the PKA substrate vasodilator-stimulated phosphoprotein. GTP-loading of Rap1 and Rap2 was evaluated via pull-down technique. Expression of Rap1, Rap2, Epac1 and Epac2 was assessed via western blot. Downregulation of Epac protein expression was achieved by siRNA. Unpaired or paired two-tailed Student's t test was used. Results The β2-agonist fenoterol augmented release of IL-8 by bradykinin. The PKA activator 6-Bnz-cAMP and the Epac activator 8-pCPT-2'-O-Me-cAMP significantly increased bradykinin-induced IL-8 release. The hydrolysis-resistant Epac activator Sp-8-pCPT-2'-O-Me-cAMPS mimicked the effects of 8-pCPT-2'-O-Me-cAMP, whereas the negative control 8-pCPT-2'-O-Me-cGMP did not. Fenoterol, forskolin and 6-Bnz-cAMP induced VASP phosphorylation, which was diminished by the PKA inhibitor Rp-8-CPT-cAMPS. 6-Bnz-cAMP and 8-pCPT-2'-O-Me-cAMP induced GTP

  16. IL-1ra Secreted by ATP-Induced P2Y2 Negatively Regulates MUC5AC Overproduction via PLCβ3 during Airway Inflammation.

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    Jeong, Jee-Yeong; Kim, Jiwook; Kim, Bokyoum; Kim, Joowon; Shin, Yusom; Kim, Judeok; Ryu, Siejeong; Yang, Yu-Mi; Song, Kyoung Seob

    2016-01-01

    Mucus secretion is often uncontrolled in many airway inflammatory diseases of humans. Identifying the regulatory pathway(s) of mucus gene expression, mucus overproduction, and hypersecretion is important to alleviate airway inflammation in these diseases. However, the regulatory signaling pathway controlling mucus overproduction has not been fully identified yet. In this study, we report that the ATP/P2Y2 complex secretes many cytokines and chemokines to regulate airway inflammation, among which IL-1 receptor antagonist (IL-1ra) downregulates MUC5AC gene expression via the inhibition of Gαq-induced Ca(2+) signaling. IL-1ra inhibited IL-1α protein expression and secretion, and vice versa. Interestingly, ATP/P2Y2-induced IL-1ra and IL-1α secretion were both mediated by PLCβ3. A dominant-negative mutation in the PDZ-binding domain of PLCβ3 inhibited ATP/P2Y2-induced IL-1ra and IL-1α secretion. IL-1α in the presence of the ATP/P2Y2 complex activated the ERK1/2 pathway in a greater degree and for a longer duration than the ATP/P2Y2 complex itself, which was dramatically inhibited by IL-1ra. These findings suggest that secreted IL-1ra exhibits a regulatory effect on ATP/P2Y2-induced MUC5AC gene expression, through inhibition of IL-1α secretion, to maintain the mucus homeostasis in the airway. Therefore, IL-1ra could be an excellent modality for regulating inflamed airway microenvironments in respiratory diseases.

  17. The laminin β1-competing peptide YIGSR induces a hypercontractile, hypoproliferative airway smooth muscle phenotype in an animal model of allergic asthma

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    Zaagsma Johan

    2010-12-01

    Full Text Available Abstract Background Fibroproliferative airway remodelling, including increased airway smooth muscle (ASM mass and contractility, contributes to airway hyperresponsiveness in asthma. In vitro studies have shown that maturation of ASM cells to a (hypercontractile phenotype is dependent on laminin, which can be inhibited by the laminin-competing peptide Tyr-Ile-Gly-Ser-Arg (YIGSR. The role of laminins in ASM remodelling in chronic asthma in vivo, however, has not yet been established. Methods Using an established guinea pig model of allergic asthma, we investigated the effects of topical treatment of the airways with YIGSR on features of airway remodelling induced by repeated allergen challenge, including ASM hyperplasia and hypercontractility, inflammation and fibrosis. Human ASM cells were used to investigate the direct effects of YIGSR on ASM proliferation in vitro. Results Topical administration of YIGSR attenuated allergen-induced ASM hyperplasia and pulmonary expression of the proliferative marker proliferating cell nuclear antigen (PCNA. Treatment with YIGSR also increased both the expression of sm-MHC and ASM contractility in saline- and allergen-challenged animals; this suggests that treatment with the laminin-competing peptide YIGSR mimics rather than inhibits laminin function in vivo. In addition, treatment with YIGSR increased allergen-induced fibrosis and submucosal eosinophilia. Immobilized YIGSR concentration-dependently reduced PDGF-induced proliferation of cultured ASM to a similar extent as laminin-coated culture plates. Notably, the effects of both immobilized YIGSR and laminin were antagonized by soluble YIGSR. Conclusion These results indicate that the laminin-competing peptide YIGSR promotes a contractile, hypoproliferative ASM phenotype in vivo, an effect that appears to be linked to the microenvironment in which the cells are exposed to the peptide.

  18. Reverse-phase phosphoproteome analysis of signaling pathways induced by Rift valley fever virus in human small airway epithelial cells.

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    Taissia G Popova

    Full Text Available Rift valley fever virus (RVFV infection is an emerging zoonotic disease endemic in many countries of sub-Saharan Africa and in Egypt. In this study we show that human small airway epithelial cells are highly susceptible to RVFV virulent strain ZH-501 and the attenuated strain MP-12. We used the reverse-phase protein arrays technology to identify phosphoprotein signaling pathways modulated during infection of cultured airway epithelium. ZH-501 infection induced activation of MAP kinases (p38, JNK and ERK and downstream transcriptional factors [STAT1 (Y701, ATF2 (T69/71, MSK1 (S360 and CREB (S133]. NF-κB phosphorylation was also increased. Activation of p53 (S15, S46 correlated with the increased levels of cleaved effector caspase-3, -6 and -7, indicating activation of the extrinsic apoptotic pathway. RVFV infection downregulated phosphorylation of a major anti-apoptotic regulator of survival pathways, AKT (S473, along with phosphorylation of FOX 01/03 (T24/31 which controls cell cycle arrest downstream from AKT. Consistent with this, the level of apoptosis inhibitor XIAP was decreased. However, the intrinsic apoptotic pathway marker, caspase-9, demonstrated only a marginal activation accompanied by an increased level of the inhibitor of apoptosome formation, HSP27. Concentration of the autophagy marker, LC3B, which often accompanies the pro-survival signaling, was decreased. Cumulatively, our analysis of RVFV infection in lung epithelium indicated a viral strategy directed toward the control of cell apoptosis through a number of transcriptional factors. Analyses of MP-12 titers in challenged cells in the presence of MAPK inhibitors indicated that activation of p38 represents a protective cell response while ERK activation controls viral replication.

  19. Upper airway collapse during drug induced sleep endoscopy: head rotation in supine position compared with lateral head and trunk position.

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    Safiruddin, Faiza; Koutsourelakis, Ioannis; de Vries, Nico

    2015-02-01

    Drug induced sedated sleep endoscopy (DISE) is often employed to determine the site, severity and pattern of obstruction in patients with sleep apnea. DISE is usually performed in supine position. We recently showed that the obstruction pattern is different when DISE is performed in lateral position. In this study, we compared the outcomes of DISE performed in supine position with head rotated, with the outcomes of DISE performed with head and trunk in lateral position. The Prospective study design was used in the present study. Sixty patients with OSA (44 male; mean apnea hypopnea index (AHI) 20.8 ± 17.5 events/h) underwent DISE under propofol sedation. Patients were placed in lateral position, and the upper airway collapse was evaluated. The patients were then placed in supine position with the head rotated to the right side. DISE outcomes were scored using the VOTE classification system. In lateral position, nine patients (15.0%) had a complete antero-posterior (A-P) collapse at the level of the velum, nine had a partial A-P collapse. During head rotation and trunk in supine position, at the level of the velum, four patients (6.7%) had a complete A-P collapse, while two patients (3.3%) had a partial A-P collapse. For all other sites, the patterns of collapse were not significantly different between head rotation and lateral position. During DISE, rotation of the head in supine position, and lateral head and trunk position present similar sites, severity and patterns of upper airway collapse, with the exception of collapse at the level of the velum. Here the severity of A-P collapse is less severe during head rotation than in lateral head and trunk position.

  20. Airway smooth muscle relaxation results from a reduction in the frequency of Ca2+ oscillations induced by a cAMP-mediated inhibition of the IP3 receptor

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    Sanderson Michael J

    2006-02-01

    Full Text Available Abstract Background It has been shown that the contractile state of airway smooth muscle cells (SMCs in response to agonists is determined by the frequency of Ca2+ oscillations occurring within the SMCs. Therefore, we hypothesized that the relaxation of airway SMCs induced by agents that increase cAMP results from the down-regulation or slowing of the frequency of the Ca2+ oscillations. Methods The effects of isoproterenol (ISO, forskolin (FSK and 8-bromo-cAMP on the relaxation and Ca2+ signaling of airway SMCs contracted with methacholine (MCh was investigated in murine lung slices with phase-contrast and laser scanning microscopy. Results All three cAMP-elevating agents simultaneously induced a reduction in the frequency of Ca2+ oscillations within the SMCs and the relaxation of contracted airways. The decrease in the Ca2+ oscillation frequency correlated with the extent of airway relaxation and was concentration-dependent. The mechanism by which cAMP reduced the frequency of the Ca2+ oscillations was investigated. Elevated cAMP did not affect the re-filling rate of the internal Ca2+ stores after emptying by repetitive exposure to 20 mM caffeine. Neither did elevated cAMP limit the Ca2+ available to stimulate contraction because an elevation of intracellular Ca2+ concentration induced by exposure to a Ca2+ ionophore (ionomycin or by photolysis of caged-Ca2+ did not reverse the effect of cAMP. Similar results were obtained with iberiotoxin, a blocker of Ca2+-activated K+ channels, which would be expected to increase Ca2+ influx and contraction. By contrast, the photolysis of caged-IP3 in the presence of agonist, to further elevate the intracellular IP3 concentration, reversed the slowing of the frequency of the Ca2+ oscillations and relaxation of the airway induced by FSK. This result implied that the sensitivity of the IP3R to IP3 was reduced by FSK and this was supported by the reduced ability of IP3 to release Ca2+ in SMCs in the presence of

  1. Effect of Preconditioning with Desflurane on Phosphorylated Glycogen Synthase Kinase 3β Contents in an Experiment

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    V. V. Likhvantsev

    2016-01-01

    Full Text Available The purpose of this study is to determine and evaluate if the preconditioning with desflurane depends on level of phosphoGSK3β.Material and methods. White outbred male rats (56 were randomly allocated to 6 groups. Ischemia/reperfusion modeling was performed using V. G.Korpachev's technique. The reference group consisted of sham (falselyoperated animals. The second group underwent global ischemia/reperfusion after anesthesia with chloral hydrate. The next two groups were treated with either sevoflurane or desflurane at 1 MAC. In the final two groups, the use of same anes thetics was followed by global ischemia/reperfusion. The concentration of phosphoGSK3β in brain homogenate was determined using western blotting. A statistical analysis was performed using the MannWhitney Utest, and the difference was considered significant at P<0.05. A threeminute ischemia with subsequent reperfusion resulted in a significant increase in the concentration of phosphoGSK3β vs. the reference group (620437 relative units vs. 304574 relative units, respectively, P<0.05. Similar results were observed in groups where animals received inhaled sevoflurane (743166 relative units and desflurane (667119 relative units alone (P<0.05. In the ischemia/reperfusion group, the concentration of phosphoGSK3β was equal to 922231 relative units after inhalation of sevoflurane (P<0.05 vs. the reference group. In the group with a combination of desflurane and ischemia/reperfusion, the enzyme concentration increased up to 677084 relative units (P<0.05 vs. reference group. No difference in concentrations of the enzyme between groups receiving inhaled anesthetics with and without ischemia/perfusion was found. In addition, the concentration of this enzyme was comparable with that in the ischemia/reperfusion group. Conclusion. Two anesthetics under testing possess similarly increased concentration of phosphoGSK3β in rat brain homogenates.

  2. Cockroach protease allergen induces allergic airway inflammation via epithelial cell activation

    Science.gov (United States)

    Kale, Sagar L.; Agrawal, Komal; Gaur, Shailendra Nath; Arora, Naveen

    2017-01-01

    Protease allergens are known to enhance allergic inflammation but their exact role in initiation of allergic reactions at mucosal surfaces still remains elusive. This study was aimed at deciphering the role of serine protease activity of Per a 10, a major cockroach allergen in initiation of allergic inflammation at mucosal surfaces. We demonstrate that Per a 10 increases epithelial permeability by disruption of tight junction proteins, ZO-1 and occludin, and enhances the migration of Monocyte derived dendritic cell precursors towards epithelial layer as exhibited by trans-well studies. Per a 10 exposure also leads to secretion of IL-33, TSLP and intracellular Ca2+ dependent increase in ATP levels. Further, in vivo experiments revealed that Per a 10 administration in mice elevated allergic inflammatory parameters along with high levels of IL-33, TSLP, IL-1α and uric acid in the mice lungs. We next demonstrated that Per a 10 cleaves CD23 (low affinity IgE receptor) from the surface of PBMCs and purified B cells and CD25 (IL-2 receptor) from the surface of PBMCs and purified T cells in an activity dependent manner, which might favour Th2 responses. In conclusion, protease activity of Per a 10 plays a significant role in initiation of allergic airway inflammation at the mucosal surfaces. PMID:28198394

  3. Pulmonary exposure to diesel exhaust particles induces airway inflammation and cytokine expression in NC/Nga mice

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    Inoue, Ken-ichiro; Yanagisawa, Rie [National Institute for Environmental Studies, Inhalation Toxicology and Pathophysiology Research Team, Tsukuba (Japan); Takano, Hirohisa [National Institute for Environmental Studies, Inhalation Toxicology and Pathophysiology Research Team, Tsukuba (Japan); Kyoto Prefectural University of Medicine, Inflammation and Immunology, Graduate School of Medical Science, Kyoto (Japan); Ichinose, Takamichi [Oita University of Nursing and Health Science, Department of Health Science, Oita (Japan); Shimada, Akinori [Tottori University, Department of Veterinary Pathology, Faculty of Agriculture, Tottori (Japan); Yoshikawa, Toshikazu [Kyoto Prefectural University of Medicine, Inflammation and Immunology, Graduate School of Medical Science, Kyoto (Japan)

    2005-10-01

    Although several studies have reported that diesel exhaust particles (DEP) affect cardiorespiratory health in animals and humans, the effect of DEP on animal models with spontaneous allergic disorders has been far less intensively studied. The Nc/Nga mouse is known to be a typical animal model for human atopic dermatitis (AD). In the present study, we investigated the effects of repeated pulmonary exposure to DEP on airway inflammation and cytokine expression in NC/Nga mice. The animals were randomized into two experimental groups that received vehicle or DEP by intratracheal instillation weekly for six weeks. Cellular profiles of bronchoalveolar lavage (BAL) fluid and expressions of cytokines and chemokines in both the BAL fluid and lung tissues were evaluated 24 h after the last instillation. The DEP challenge produced an increase in the numbers of total cells, neutrophils, and mononuclear cells in BAL fluid as compared to the vehicle challenge (P<0.01). DEP exposure significantly induced the lung expressions of interleukin (IL)-4, keratinocyte chemoattractant (KC), and macrophage inflammatory protein (MIP)-1{alpha} when compared to the vehicle challenge. These results indicate that intratracheal exposure to DEP induces the recruitment of inflammatory cells, at least partially, through the local expression of IL-4 and chemokines in NC/Nga mice. (orig.)

  4. Suppression of ovalbumin-induced airway inflammatory responses in a mouse model of asthma by Mimosa pudica extract.

    Science.gov (United States)

    Yang, Eun Ju; Lee, Ji-Sook; Yun, Chi-Young; Ryang, Yong Suk; Kim, Jong-Bae; Kim, In Sik

    2011-01-01

    Asthma is an inflammatory airway disease. The pathogenic mechanisms of asthma include the infiltration of leukocytes and release of cytokines. Mimosa pudica (Mp) has been used traditionally for the treatment of insomnia, diarrhea and inflammatory diseases. Although Mp extract has various therapeutic properties, the effect of this extract on asthma has not yet been reported. This study investigated the suppressive effects of Mp extract on asthmatic responses both in vitro and in vivo. Mp extract was acquired from dried and powdered whole plants of M. pudica using 80% ethanol. BALB/c mice were used for the mouse model of asthma induced by ovalbumin. Mp extract significantly inhibited the HMC-1 cell migration induced by stem cell factor and blocked the release of monocyte chemotactic protein-1 (MCP-1) and interleukin-6 (IL-6) in EoL-1 cells. Leukocytosis, eosinophilia and mucus hypersecretion in asthmatic lung were significantly suppressed by Mp extract. The release of ovalbumin-specific IgE in bronchoalveolar lavage fluid and serum was also decreased. Mp extract treatment resulted in no liver cytotoxicity. The Mp extract has inhibitory properties on asthma and may be used as a potent therapeutic agent for allergic lung inflammation. Copyright © 2010 John Wiley & Sons, Ltd.

  5. Dianthus superbus fructus suppresses airway inflammation by downregulating of inducible nitric oxide synthase in an ovalbumin-induced murine model of asthma

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    Shin In-Sik

    2012-10-01

    Full Text Available Abstract Background Dianthus superbus has long been used as a herbal medicine in Asia and as an anti-inflammatory agent. In this study, we evaluated the anti-inflammatory effects of Dianthus superbus fructus ethanolic extract (DSE on Th2-type cytokines, eosinophil infiltration, and other factors in an ovalbumin (OVA-induced murine asthma model. To study the possible mechanism of the anti-inflammatory effect of DSE, we also evaluated the expression of inducible nitric oxide synthase (iNOS in the respiratory tract. Methods Mice were sensitized on days 0 and 14 by intraperitoneal injection of OVA. On days 21, 22 and 23 after initial sensitization, mice received an airway challenge with OVA for 1 h using an ultrasonic nebulizer. DSE was applied 1 h prior to OVA challenge. Mice were administered DSE orally at doses of 100 mg/kg or 200 mg/kg once daily from day 18 to 23. Bronchoalveolar lavage fluid (BALF was collected 48 h after the final OVA challenge. Levels of interleukin (IL-4, IL-13 and eotaxin in BALF were measured using enzyme-linked immunosorbent assays (ELISAs. Lung tissue sections were stained with hematoxylin and eosin for assessment of cell infiltration and mucus production with periodic acid shift staining, in conjunction with ELISA and western blot analyses for iNOS expression. Results DSE significantly reduced the levels of IL-4, IL-13, eotaxin, and immunoglobulin (Ig E, number of inflammatory cells in BALF, and inflammatory cell infiltration and mucus production in the respiratory tract. DSE also attenuated the overexpression of iNOS protein induced by OVA challenge. Conclusion Our results suggest that DSE effectively protects against allergic airway inflammation by downregulating of iNOS expression and that DSE has potential as a therapeutic agent for allergic asthma.

  6. Virulence Factors of Pseudomonas aeruginosa Induce Both the Unfolded Protein and Integrated Stress Responses in Airway Epithelial Cells.

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    Emily F A van 't Wout

    2015-06-01

    Full Text Available Pseudomonas aeruginosa infection can be disastrous in chronic lung diseases such as cystic fibrosis and chronic obstructive pulmonary disease. Its toxic effects are largely mediated by secreted virulence factors including pyocyanin, elastase and alkaline protease (AprA. Efficient functioning of the endoplasmic reticulum (ER is crucial for cell survival and appropriate immune responses, while an excess of unfolded proteins within the ER leads to "ER stress" and activation of the "unfolded protein response" (UPR. Bacterial infection and Toll-like receptor activation trigger the UPR most likely due to the increased demand for protein folding of inflammatory mediators. In this study, we show that cell-free conditioned medium of the PAO1 strain of P. aeruginosa, containing secreted virulence factors, induces ER stress in primary bronchial epithelial cells as evidenced by splicing of XBP1 mRNA and induction of CHOP, GRP78 and GADD34 expression. Most aspects of the ER stress response were dependent on TAK1 and p38 MAPK, except for the induction of GADD34 mRNA. Using various mutant strains and purified virulence factors, we identified pyocyanin and AprA as inducers of ER stress. However, the induction of GADD34 was mediated by an ER stress-independent integrated stress response (ISR which was at least partly dependent on the iron-sensing eIF2α kinase HRI. Our data strongly suggest that this increased GADD34 expression served to protect against Pseudomonas-induced, iron-sensitive cell cytotoxicity. In summary, virulence factors from P. aeruginosa induce ER stress in airway epithelial cells and also trigger the ISR to improve cell survival of the host.

  7. Involvement of the MAPK and PI3K pathways in chitinase 3-like 1-regulated hyperoxia-induced airway epithelial cell death

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    Kim, Mi Na; Lee, Kyung Eun; Hong, Jung Yeon; Heo, Won Il; Kim, Kyung Won; Kim, Kyu Earn [Department of Pediatrics and Institute of Allergy, Severance Medical Research Institute, Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, Seoul (Korea, Republic of); Sohn, Myung Hyun, E-mail: mhsohn@yuhs.ac [Department of Pediatrics and Institute of Allergy, Severance Medical Research Institute, Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, Seoul (Korea, Republic of)

    2012-05-18

    Highlights: Black-Right-Pointing-Pointer Hyperoxia induces apoptosis and chitinase 3-like 1 expression in human airway epithelial cells. Black-Right-Pointing-Pointer Presence of chitinase 3-like 1 affects airway epithelial cell death after hyperoxic exposure. Black-Right-Pointing-Pointer Silencing chitinase 3-like 1 manipulate the phosphorylation of ERK, p38 and Akt. -- Abstract: Background: Exposure to 100% oxygen causes hyperoxic acute lung injury characterized by cell death and injury of alveolar epithelial cells. Recently, the role of chitinase 3-like 1 (CHI3L1), a member of the glycosyl hydrolase 18 family that lacks chitinase activity, in oxidative stress was demonstrated in murine models. High levels of serum CHI3L1 have been associated with various diseases of the lung, such as asthma, chronic obstructive pulmonary disease, and cancer. However, the role of CHI3L1 in human airway epithelial cells undergoing oxidative stress remains unknown. In addition, the signaling pathways associated with CHI3L1 in this process are poorly understood. Purpose: In this study, we demonstrate the role of CHI3L1, along with the MAPK and PI3K signaling pathways, in hyperoxia-exposed airway epithelial cells. Method: The human airway epithelial cell line, BEAS-2B, was exposed to >95% oxygen (hyperoxia) for up to 72 h. Hyperoxia-induced cell death was determined by assessing cell viability, Annexin-V FITC staining, caspase-3 and -7 expression, and electron microscopy. CHI3L1 knockdown and overexpression studies were conducted in BEAS-2B cells to examine the role of CHI3L1 in hyperoxia-induced apoptosis. Activation of the MAPK and PI3K pathways was also investigated to determine the role of these signaling cascades in this process. Results: Hyperoxia exposure increased CHI3L1 expression and apoptosis in a time-dependent manner. CHI3L1 knockdown protected cells from hyperoxia-induced apoptosis. In contrast, CHI3L1 overexpression promoted cell death after hyperoxia exposure. Finally

  8. Alternaria-induced release of IL-18 from damaged airway epithelial cells: an NF-κB dependent mechanism of Th2 differentiation?

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    Hiroki Murai

    Full Text Available BACKGROUND: A series of epidemiologic studies have identified the fungus Alternaria as a major risk factor for asthma. The airway epithelium plays a critical role in the pathogenesis of allergic asthma. These reports suggest that activated airway epithelial cells can produce cytokines such as IL-25, TSLP and IL-33 that induce Th2 phenotype. However the epithelium-derived products that mediate the pro-asthma effects of Alternaria are not well characterized. We hypothesized that exposure of the airway epithelium to Alternaria releasing cytokines that can induce Th2 differentiation. METHODOLOGY/PRINCIPAL FINDING: We used ELISA to measure human and mouse cytokines. Alternaria extract (ALT-E induced rapid release of IL-18, but not IL-4, IL-9, IL-13, IL-25, IL-33, or TSLP from cultured normal human bronchial epithelial cells; and in the BAL fluids of naïve mice after challenge with ALT-E. Both microscopic and FACS indicated that this release was associated with necrosis of epithelial cells. ALT-E induced much greater IL-18 release compared to 19 major outdoor allergens. Culture of naïve CD4 cells with rmIL-18 induced Th2 differentiation in the absence of IL-4 and STAT6, and this effect was abrogated by disrupting NF- κB p50 or with a NEMO binding peptide inhibitor. CONCLUSION/SIGNIFICANCE: Rapid and specific release of IL-18 from Alternaria-exposed damaged airway epithelial cells can directly initiate Th2 differentiation of naïve CD4(+ T-cells via a unique NF-κB dependent pathway.

  9. Single and repeated sevoflurane or desflurane exposure does not impair spatial memory performance of young adult mice.

    Science.gov (United States)

    Kilicaslan, Alper; Belviranli, Muaz; Okudan, Nilsel; Nurullahoglu Atalik, Esra

    2013-12-01

    Volatile anesthetics are known to disturb the spatial memory in aged rodents, but there is insufficient information on their effects on young adult rodents. The aim of this study was to compare the effects of single and repeated exposure to desflurane and sevoflurane on spatial learning and memory functions in young adult mice. Balb/c mice (2 months old) were randomly divided into six equal groups (n = 8). The groups with single inhalation were exposed to 3.3% sevoflurane or 7.8% desflurane or vehicle gas for 4 h, respectively. The groups with repeated inhalation were exposed to 3.3% sevoflurane or 7.8% desflurane or vehicle gas for 2 h a day during 5 consecutive days. Spatial learning and memory were tested in the Morris water maze 24 h after exposure. In the learning phase, the parameters associated with finding the hidden platform and swimming speed, and in the memory phase, time spent in the target quadrant and the adjacent quadrants, were assessed and compared between the groups. In the 4-day learning process, there was no significant difference between the groups in terms of mean latency to platform, mean distance traveled and average speed (P > 0.05). During the memory-test phase, all mice exhibited spatial memory, but there was no significant difference between the groups in terms of time spent in the target quadrant (P > 0.05). Sevoflurane and desflurane anesthesia did not impair acquisition learning and retention memory in young adult mice.

  10. Corticosteroid administration modifies ozone-induced increases in sheep airway blood flow

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    Gunther, R.A.; Yousef, M.A.; Schelegle, E.S.; Cross, C.E. (Department of Surgery, School of Medicine, University of California, Davis (United States))

    1992-09-01

    Recently, we have shown that exposure of intubated conscious sheep to 3 to 4 ppm ozone (O3) for 3 h increases bronchial blood flow (Qbr). The purpose of the present study was to assess the potential role of corticosteroids in modulating this increase. Six nasally intubated sheep were exposed to filtered room air, 3.5 ppm O3 on two separate occasions, and 3.5 ppm O3 plus methyl-prednisone, for 3 h. Qbr was measured using a chronically implanted 20 MHz pulsed Doppler flow probe. Qbr, mean aortic pressure, cardiac output, pulmonary artery pressure, arterial blood gases, and core temperature were monitored. After 3 h of 3.5 ppm O3, Qbr increased from 3.2 +/- 0.5 (mean +/- SEM) to 8.5 +/- 1.6 KHz, whereas bronchial vascular resistance (BVR) decreased from the baseline value of 43.6 +/- 8.0 to 15.0 +/- 3 mm Hg/KHz. With corticosteroids, baseline Qbr was 3.2 +/- 0.6 and BVR was 44.2 +/- 9.7; after 3 h of 3.5 ppm O3, Qbr was 3.3 +/- 0.5 KHz and BVR was 39.0 +/- 8.0 mm Hg/KHz. The two 3.5-ppm O3 exposures without corticosteroids were impressively reproducible. Except for Qbr and BVR, no other measured cardiovascular parameters were affected by O3. The results indicate that corticosteroids are capable of interfering with mediator, neurohumoral, or inflammatory cell mechanisms responsible for vasodilation of the airway microcirculation after O3 exposure, but do not specifically address the specific processes whereby this attenuation occurs.

  11. Comparison of the Effects of Sevoflurane, Desflurane and Totally Intravenous Anaesthesia with Propofol on Haemodynamic Variables Using Transesophageal Doppler

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    Selen Osmanagaoglu

    2008-01-01

    Full Text Available Sevoflurane and desflurane inhalation anaesthetics are in routine use providing more rapid recovery than pre-existing inhalation anaesthetics. We wanted to compare the effect of different anaesthetic agents on haemodynamic parameters with using transesophageal echo-Doppler in ASA I-II patients. A total of 45 American Society of Anes-thesiologists (ASA physical status I-II patients age between 18-65 scheduled for elective major abdominal surgery were admitted to this prospective randomized study and divided into three groups. Induction of anaesthesia was provided with 1µgkg -1 fentanyl, 6-8 mgkg -1 thiopenthal and 0.1 mgkg -1 vecuronium in sevoflurane (Group S, n=15, and desflurane (Group D, n=15, and 1µgkg -1 remifentanil, 2mgkg -1 propofol, and 0.1 mgkg -1 vecuronium in totally intrave-nous anaesthesia (TIVA group (Group T; n=15. For maintenance of anaesthesia, patients received an infusion of 0.15 µgkg -1 min remifentanil, 4-6 mgkg -1 h -1 propofol, sevoflurane 2%, or desflurane 6% at 1.0 MAC. Bispectral index (BIS values of 40-60 were targeted during operation. After endotracheal intubation, the haemodynamic and respira-tory parameters, and BIS were recorded 5 min after the intubation (T 0 , 30 min after the intubation (T 1 , 60 min after the intubation (T 2 and before the extubation (T 3 with using haemodynamic monitoring (Hemosonic 100. After induction of anaesthetic agents, heart rate (HR increased significantly in desflurane group (Group D compared with group sevoflurane (Group S and TIVA (Group T groups at 5 min after the intubations, 30 min after the intubations, 60 min after the intubations and compared with group sevoflurane before the extubation. The Stroke Volume (SV values increased significantly at the 5th minute intubation in Group S as compared to the Group D and in Group D as compared to the Group T. Compared with Group D, maximum acceleration (Acc increased significanly in Group T before extubation. The BIS values were

  12. Comparison of the incidence of emergence agitation and emergence times between desflurane and sevoflurane anesthesia in children

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    Lim, Byung Gun; Lee, Il Ok; Ahn, Hyeongsik; Lee, Dong Kyu; Won, Young Ju; Kim, Hyun Jung; Kim, Heezoo

    2016-01-01

    Abstract Background: The differences in the incidence and severity of emergence agitation (EA) and emergence times between desflurane and sevoflurane anesthesia have not been as clearly elucidated in children as in adults. Methods: The design of the study is a systematic review with meta-analysis of randomized controlled trials. The study methodology is based on the Cochrane Review Methods. A comprehensive literature search was conducted to identify clinical trials comparing the incidence or severity of EA and emergence times in children anesthetized with desflurane or sevoflurane. Two reviewers independently assessed each study according to predefined inclusion criteria and extracted data from each study using a prespecified data extraction form. The data from each study were combined using a fixed effect or random effect model to calculate the pooled risk ratio (RR) or standardized mean difference (SMD) and 95% confidence interval (CI). Funnel plots were used to assess publication bias. Subgroup and sensitivity analyses were performed. Results: Fourteen studies met the inclusion criteria. Among the 1196 patients in these 14 studies, 588 received desflurane anesthesia and 608 received sevoflurane anesthesia. The incidence of EA was comparable between the 2 groups (pooled RR = 1.21; 95% CI: 0.96–1.53; I2 = 26%), and so was the severity of EA (EA score) between the 2 groups (SMD = 0.12; 95% CI: −0.02 to 0.27; I2 = 0%). Extubation and awakening times were shorter in the desflurane group than in the sevoflurane group; the weighted mean differences were −2.21 (95% CI: −3.62 to −0.81; I2 = 93%) and −2.74 (95% CI: −3.80 to −1.69; I2 = 85%), respectively. No publication bias was found in the funnel plot. The subgroup analysis based on the type of EA scale showed a higher incidence of EA in the desflurane group than in the sevoflurane group in studies using 3-, 4-, or 5-point EA scales; the pooled RR was 1.38 (95% CI: 1.10–1.73; I2 = 37%). Conclusion: The

  13. Activation of the Prostaglandin E2 receptor EP2 prevents house dust mite-induced airway hyperresponsiveness and inflammation by restraining mast cells' activity.

    Science.gov (United States)

    Serra-Pages, M; Torres, R; Plaza, J; Herrerias, A; Costa-Farré, C; Marco, A; Jiménez, M; Maurer, M; Picado, C; de Mora, F

    2015-10-01

    Prostaglandin E2 (PGE2 ) has been proposed to exert antiasthmatic effects in patients, to prevent antigen-induced airway pathology in murine models, and to inhibit mast cells (MC) activity in vitro. To assess in a murine model whether the protective effect of PGE2 may be a consequence of its ability to activate the E-prostanoid (EP)2 receptor on airway MC. Either BALB/c or C57BL/6 mice were exposed intranasally (i.n.) to house dust mite (HDM) aeroallergens. Both strains were given PGE2 locally (0.3 mg/kg), but only BALB/c mice were administered butaprost (EP2 agonist: 0.3 mg/kg), or AH6809 (EP2 antagonist; 2.5 mg/kg) combined with the MC stabilizer sodium cromoglycate (SCG: 25 mg/kg). Airway hyperresponsiveness (AHR) and inflammation, along with lung MC activity, were evaluated. In addition, butaprost's effect was assessed in MC-mediated passive cutaneous anaphylaxis (PCA) in mice challenged with 2,4-dinitrophenol (DNP). Selective EP2 agonism attenuated aeroallergen-caused AHR and inflammation in HDM-exposed BALB/c mice, and this correlated with a reduced lung MC activity. Accordingly, the blockade of endogenous PGE2 by means of AH6809 worsened airway responsiveness in sensitive BALB/c mice, and such worsening was reversed by SCG. The relevance of MC to PGE2 -EP2 driven protection was further highlighted in MC-dependent PCA, where butaprost fully prevented MC-induced ear swelling. Unlike in BALB/c mice, PGE2 did not protect the airways of HDM-sensitized C57BL/6 animals, a strain in which we showed MC to be irrelevant to aeroallergen-driven AHR and inflammation. The beneficial effect of both exogenous and endogenous PGE2 in aeroallergen-sensitized mice may be attributable to the activation of the EP2 receptor, which in turn acts as a restrainer of airway MC activity. This opens a path towards the identification of therapeutic targets against asthma along the 'EP2 -MC-airway' axis. © 2015 John Wiley & Sons Ltd.

  14. Clonorchis sinensis-derived total protein attenuates airway inflammation in murine asthma model by inducing regulatory T cells and modulating dendritic cell functions

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    Jeong, Young-Il [Div. of Malaria and Parasitic Diseases, Korea Centers for Disease Control and Prevention, Osong (Korea, Republic of); Kim, Seung Hyun [Div. of AIDS, National Institute of Health, Korea Centers for Disease Control and Prevention, Osong (Korea, Republic of); Ju, Jung Won; Cho, Shin Hyeong; Lee, Won Ja [Div. of Malaria and Parasitic Diseases, Korea Centers for Disease Control and Prevention, Osong (Korea, Republic of); Park, Jin Wook; Park, Yeong-Min [Dept. of Microbiology and Immunology, College of Medicine, Pusan National University, Yang-San (Korea, Republic of); Lee, Sang Eun, E-mail: ondalgl@cdc.go.kr [Div. of Malaria and Parasitic Diseases, Korea Centers for Disease Control and Prevention, Osong (Korea, Republic of)

    2011-04-22

    Highlights: {yields} Treatment with Clonorchis sinensis-derived total protein attenuates OVA-induced airway inflammation and AHR to methacholine. {yields} Induction of CD4{sup +}CD25{sup +}Foxp3{sup +} T cells and IL-10 along with suppression of splenocyte proliferation by C. sinensis-derived total protein. {yields} C. sinensis-derived total protein interferes with the expression of co-stimulatory molecules in DCs. -- Abstract: Asthma is characterized by Th2-mediated inflammation, resulting in airway hyperresponsiveness (AHR) through airway remodeling. Recent epidemiological and experimental reports have suggested an inverse relationship between the development of allergy and helminth infections. Infection by Clonorchis sinensis, a liver fluke that resides in the bile duct of humans, is endemic predominantly in Asia including Korea and China. Using a murine model for asthma, we investigated the effects of C. sinensis-derived total protein (Cs-TP) on allergen-induced airway inflammation and the mechanism underlying the protective effects of Cs-TP administration on asthma. Treatment with Cs-TP attenuated OVA-induced airway inflammation and methacholine-induced AHR, as well as eosinophilia development, lymphocyte infiltration into the lung, and goblet cell metaplasia. This protective effect of Cs-TP is associated with markedly reduced OVA-specific IgE and Th1/Th2 cytokine production. Moreover, Cs-TP increased the number of CD4{sup +}CD25{sup +}Foxp3{sup +} regulatory T (Treg) cells as well as their suppressive activity. In fact, proliferation of OVA-restimulated splenocytes was suppressed significantly. Cs-TP also inhibited the expression of such co-stimulatory molecules as CD80, CD86, and CD40 in LPS- or OVA-stimulated dendritic cells (DCs), suggesting that Cs-TP could interfere with the capacity of airway DCs to prime naive T cells. These data demonstrate the capacity of C. sinensis to ameliorate allergic asthma and broaden our understanding of the paradoxical

  15. Effects of the Traditional Chinese Medicine Dilong on Airway Remodeling in Rats with OVA-induced-Asthma

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    Chen Yujuan

    2016-01-01

    Full Text Available The present study focuses on the effects and suggests possible mechanisms of the traditional Chinese medicine Dilong as compared to dexamethasone on lower respiratory tract remodeling in rats with asthma. The number of leukocytes and eosinophils in blood from the inferior vena cava and bronchoalveolar lavage fluid (BALF were counted. Lung tissues underwent hematoxylin and eosin staining. The thickness of the basement membrane and smooth muscle or the airways, and the ratio of inner to outer diameter of the airway wall were measured. Levels of transforming growth factor β1 (TGF-β1, matrix metallopeptidase 9/tissue inhibitor of metalloproteinase 1 (MMP-9/TIMP-1, urokinase plasminogen activator (uPA, plasminogen activator inhibitor 1 (PAI-1, and c-Myc(mRNA were evaluated. Results indicate that treatment with Dilong decreased the number of eosinophils in blood and BALF, decreased levels of TGF-β1, MMP-9/TIMP-1, uPA, PAI-1 and c-Myc, and ameliorated the thickening of airway walls, airway basement membrane and airway smooth muscle. Co-treatment with dexamethasone was found to intensity these effects. The cellularity of eosinophils and thickness of the airway basement membrane and smooth muscle were positively correlated with levels of TGF- 1, uPA, and c-Myc. Treatment with Dilong, either alone or in combination with dexamethasone, could inhibit and partly reverse airway remodeling in rats with asthma at an early stage.

  16. Antigen-sensitized CD4+CD62Llow memory/effector T helper 2 cells can induce airway hyperresponsiveness in an antigen free setting

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    Nagatani Katsuya

    2005-05-01

    Full Text Available Abstract Background Airway hyperresponsiveness (AHR is one of the most prominent features of asthma, however, precise mechanisms for its induction have not been fully elucidated. We previously reported that systemic antigen sensitization alone directly induces AHR before development of eosinophilic airway inflammation in a mouse model of allergic airway inflammation, which suggests a critical role of antigen-specific systemic immune response itself in the induction of AHR. In the present study, we examined this possibility by cell transfer experiment, and then analyzed which cell source was essential for this process. Methods BALB/c mice were immunized with ovalbumin (OVA twice. Spleen cells were obtained from the mice and were transferred in naive mice. Four days later, AHR was assessed. We carried out bronchoalveolar lavage (BAL to analyze inflammation and cytokine production in the lung. Fluorescence and immunohistochemical studies were performed to identify T cells recruiting and proliferating in the lung or in the gut of the recipient. To determine the essential phenotype, spleen cells were column purified by antibody-coated microbeads with negative or positive selection, and transferred. Then, AHR was assessed. Results Transfer of spleen cells obtained from OVA-sensitized mice induced a moderate, but significant, AHR without airway antigen challenge in naive mice without airway eosinophilia. Immunization with T helper (Th 1 elicited antigen (OVA with complete Freund's adjuvant did not induce the AHR. Transferred cells distributed among organs, and the cells proliferated in an antigen free setting for at least three days in the lung. This transfer-induced AHR persisted for one week. Interleukin-4 and 5 in the BAL fluid increased in the transferred mice. Immunoglobulin E was not involved in this transfer-induced AHR. Transfer of in vitro polarized CD4+ Th2 cells, but not Th1 cells, induced AHR. We finally clarified that CD4+CD62Llow memory

  17. Comparison of airway measurements during influenza-induced tachypnea in infant and adult cotton rats

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    Prince Gregory A

    2009-06-01

    Full Text Available Abstract Background Increased respiratory rate (tachypnea is frequently observed as a clinical sign of influenza pneumonia in pediatric patients admitted to the hospital. We previously demonstrated that influenza infection of adult cotton rats (Sigmodon hispidus also results in tachypnea and wanted to establish whether this clinical sign was observed in infected infant cotton rats. We hypothesized that age-dependent differences in lung mechanics result in differences in ventilatory characteristics following influenza infection. Methods Lung tidal volume, dynamic elastance, resistance, and pleural pressure were measured in a resistance and compliance system on mechanically-ventilated anesthestized young (14–28 day old and adult (6–12 week old cotton rats. Animals at the same age were infected with influenza virus, and breathing rates and other respiratory measurements were recorded using a whole body flow plethysmograph. Results Adult cotton rats had significantly greater tidal volume (TV, and lower resistance and elastance than young animals. To evaluate the impact of this increased lung capacity and stiffening on respiratory disease, young and adult animals were infected intra-nasally with influenza A/Wuhan/359/95. Both age groups had increased respiratory rate and enhanced pause (Penh during infection, suggesting lower airway obstruction. However, in spite of significant tachypnea, the infant (unlike the adult cotton rats maintained the same tidal volume, resulting in an increased minute volume. In addition, the parameters that contribute to Penh were different: while relaxation time between breaths and time of expiration was decreased in both age groups, a disproportionate increase in peak inspiratory and expiratory flow contributed to the increase in Penh in infant animals. Conclusion While respiratory rate is increased in both adult and infant influenza-infected cotton rats, the volume of air exchanged per minute (minute volume is

  18. Protective Effects of Fluticasone on Allergen-Induced Airway Responses and Sputum Inflammatory Markers

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    Krishnan Parameswaran

    2000-01-01

    Full Text Available BACKGROUND: A direct comparison of the protective effects of single and regular doses of inhaled glucocorticoid on allergen-induced asthmatic responses and inflammation has not been made.

  19. Muscarinic M3 receptor stimulation increases cigarette smoke-induced IL-8 secretion by human airway smooth muscle cells

    NARCIS (Netherlands)

    Gosens, R.; Rieks, D.; Meurs, H.; Ninaber, D. K.; Rabe, K. F.; Nanninga, J.; Kolahian, S.; Halayko, A. J.; Hiemstra, P. S.; Zuyderduyn, S.

    2009-01-01

    Acetylcholine is the primary parasympathetic neurotransmitter in the airways and is known to cause bronchoconstriction and mucus secretion. Recent findings suggest that acetylcholine also regulates aspects of remodelling and inflammation through its action on muscarinic receptors. In the present

  20. Muscarinic M3 receptor stimulation increases cigarette smoke-induced IL-8 secretion by human airway smooth muscle cells

    NARCIS (Netherlands)

    Gosens, R.; Rieks, D.; Meurs, H.; Ninaber, D. K.; Rabe, K. F.; Nanninga, J.; Kolahian, S.; Halayko, A. J.; Hiemstra, P. S.; Zuyderduyn, S.

    2009-01-01

    Acetylcholine is the primary parasympathetic neurotransmitter in the airways and is known to cause bronchoconstriction and mucus secretion. Recent findings suggest that acetylcholine also regulates aspects of remodelling and inflammation through its action on muscarinic receptors. In the present stu

  1. The potential effect of the angiotensin II receptor blocker telmisartan in regulating OVA-induced airway remodeling in experimental rats.

    Science.gov (United States)

    Abdel-Fattah, Maha M; Salama, Abeer A A; Shehata, Basim A; Ismaiel, Ismaiel E

    2015-10-01

    Bronchial asthma is a true ascending clinical problem. Angiotensin II is now accused to be potentially implicated in its pathogenesis, being a potent pro-inflammatory mediator with remodeling effects. This study aims to evaluate the possible protective effect of telmisartan, an angiotensin II receptor blocker, on experimentally-induced bronchial asthma. Animals were divided into 5 groups; a normal control group, an asthma control group, a reference treatment group, receiving dexamethasone, and two treatment groups, receiving telmisartan in two dose levels. Bronchial asthma was induced by intraperitoneal sensitization followed by intranasal challenge with ovalbumin (OVA). Test agents were administered prior to each intranasal OVA challenge. Lung function tests, namely tidal volume (TV) and peak expiratory flow rate (PEF) were assessed 1h after the last challenge. One day after the last challenge, absolute eosinophil counts (AEC) in blood and bronchoalveolar lavage fluids (BALF) were assessed. Serum immunoglobulin E (IgE) as well as BALF total nitrate/nitrite (NOx) were assessed. Oxidative and inflammatory biomarkers, namely lung tissue superoxide dismutase (SOD), glutathione reduced (GSH), tumor necrosis factor-alpha (TNF-α) and interleukin-5 (IL-5), were also assessed, in addition to histopathological study. Telmisartan administration in both doses significantly improved TV, PEF, AEC, IgE, NOx, GSH, SOD, TNF-α and IL-5 values compared to asthma control values. Histopathological study strongly supported the results of biochemical estimations, particularly regarding airway remodeling. These results suggest that telmisartan may have potential protecting effects against experimental bronchial asthma, probably due to its bronchodilator, antioxidant and anti-inflammatory effects. Copyright © 2015 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  2. Cigarette Smoke-Induced Collagen Destruction; Key to Chronic Neutrophilic Airway Inflammation?

    NARCIS (Netherlands)

    Overbeek, Saskia A.; Braber, Saskia; Koelink, Pim J.; Henricks, Paul A. J.; Mortaz, Esmaeil; Loi, Adele T. LoTam; Jackson, Patricia L.; Garssen, Johan; Wagenaar, Gerry T. M.; Timens, Wim; Koenderman, Leo; Blalock, J. Edwin; Kraneveld, Aletta D.; Folkerts, Gert

    2013-01-01

    Background: Cigarette smoking induces inflammatory responses in all smokers and is the major risk factor for lung disease such as chronic obstructive pulmonary disease (COPD). In this progressive disease, chronic inflammation in the lung contributes to lung tissue destruction leading to the formatio

  3. Rhinovirus infection induces procoagulant changes in parallel with eosinophilic airway inflammation

    NARCIS (Netherlands)

    Majoor, C.J.; Kamphuisen, P.W.; Van De Pol, M.A.; Meijers, J.C.; Van Der Poll, T.; Nieuwland, R.; Johnston, S.L.; Bel, E.H.; Lutter, R.; Van Der Sluijs, K.F.

    2013-01-01

    Background: Asthma exacerbations are frequently triggered by rhinovirus infections. Asthma itself is associated with activated coagulation and increased risk of venous thromboembolism1 and also respiratory viruses may activate hemostasis. Vice versa, a prothrombotic state in the lung can also induce

  4. Human rhinovirus induced cytokine/chemokine responses in human airway epithelial and immune cells.

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    Devi Rajan

    Full Text Available Infections with human rhinovirus (HRV are commonly associated with acute upper and lower respiratory tract disease and asthma exacerbations. The role that HRVs play in these diseases suggests it is important to understand host-specific or virus-specific factors that contribute to pathogenesis. Since species A HRVs are often associated with more serious HRV disease than species B HRVs, differences in immune responses they induce should inform disease pathogenesis. To identify species differences in induced responses, we evaluated 3 species A viruses, HRV 25, 31 and 36 and 3 species B viruses, HRV 4, 35 and 48 by exposing human PBMCs to HRV infected Calu-3 cells. To evaluate the potential effect of memory induced by previous HRV infection on study responses, we tested cord blood mononuclear cells that should be HRV naïve. There were HRV-associated increases (significant increase compared to mock-infected cells for one or more HRVs for IP-10 and IL-15 that was unaffected by addition of PBMCs, for MIP-1α, MIP-1β, IFN-α, and HGF only with addition of PBMCs, and for ENA-78 only without addition of PBMCs. All three species B HRVs induced higher levels, compared to A HRVs, of MIP-1α and MIP-1β with PBMCs and ENA-78 without PBMCs. In contrast, addition of CBMCs had less effect and did not induce MIP-1α, MIP-1β, or IFN-α nor block ENA-78 production. Addition of CBMCs did, however, increase IP-10 levels for HRV 35 and HRV 36 infection. The presence of an effect with PBMCs and no effect with CBMCs for some responses suggest differences between the two types of cells possibly because of the presence of HRV memory responses in PBMCs and not CBMCs or limited response capacity for the immature CBMCs relative to PBMCs. Thus, our results indicate that different HRV strains can induce different patterns of cytokines and chemokines; some of these differences may be due to differences in memory responses induced by past HRV infections, and other differences

  5. Inhibitory effect of n-butanol fraction of Moringa oleifera Lam. seeds on ovalbumin-induced airway inflammation in a guinea pig model of asthma.

    Science.gov (United States)

    Mahajan, Shailaja G; Banerjee, Aryamitra; Chauhan, Bhupendrasinh F; Padh, Harish; Nivsarkar, Manish; Mehta, Anita A

    2009-01-01

    Moringaceae, which belongs to the Moringa oleifera Lam. family, is a well-known herb used in Asian medicine as an antiallergic drug. In the present study, the efficacy of the n-butanol extract of the seeds of the plant (MONB) is examined against ovalbumin-induced airway inflammation in guinea pigs. The test drugs (MONB or dexamethasone) are administered orally prior to challenge with aerosolized 0.5% ovalbumin. During the experimental period, bronchoconstriction tests are performed, and lung function parameters are measured. The blood and bronchoalveolar lavage fluid are collected to assess cellular content, and serum is used for cytokine (tumor necrosis factor-alpha, interleukin-4, and interleukin-6) assays. Histamine assays of lung tissue are performed using lung tissue homogenate. The results suggest that in ovalbumin-sensitized model control animals, tidal volume is decreased, respiration rate is increased, and both the total and differential cell counts in blood and bronchoalveolar lavage fluid are increased significantly compared with nonsensitized controls. MONB treatment shows improvement in all parameters except bronchoalveolar lavage tumor necrosis factor-alpha and interleukin-4. Moreover, MONB treatment demonstrates protection against acetylcholine-induced bronchoconstriction and airway inflammation. These results indicate that MONB has an inhibitory effect on airway inflammation. Thus, MONB possesses an antiasthmatic property through modulation of the relationship between Th1/Th2 cytokine imbalances.

  6. 5-Aminosalicylic acid attenuates allergen-induced airway inflammation and oxidative stress in asthma.

    Science.gov (United States)

    Raju, K Rama Satyanarayana; Kumar, M N Sathish; Gupta, Saurabh; Naga, Srinivas T; Shankar, Jaya K; Murthy, Vishakantha; Madhunapanthula, Subba Rao V; Mulukutla, Shashank; Ambhore, Nilesh S; Tummala, Shashank; Vishnuvarthan, V J; Azam, Afzal; Elango, Kannan

    2014-12-01

    Pro-inflammatory cytokines regulate the magnitude of allergic reactions during asthma. Tumor necrosis factor--alpha (TNF-α), interleukin-6 (IL-6) and interleukin-13 (IL-13) play a crucial role in aggravating the inflammatory conditions during allergic asthma. In addition, oxidative stress contributes to the pathogenesis of asthma by altering the physiological condition resulting in the development of status asthmaticus. Anti-inflammatory corticosteroids are being widely used for treating allergic asthma. In the present study 5-aminosalicylic acid (5-ASA), a salicylic acid derivative, was evaluated, in vivo for its potential to suppress TNF-α, IL-6 and IL-13 using ovalbumin (OVA) induced allergic asthma in Balb/C mice. Oral administration of 65, 130 and 195 mg/kg 5-ASA significantly reduced the OVA induced total and differential leucocyte count, TNF-α, IL-6, IL-13, nitrite, nitrate, MDA, MPO and TPL levels in the lung lavage samples. Collectively, these findings suggest that 5-ASA is a potent immunomodulator and suppresses key Th2 cytokines production and oxidative stress in OVA-induced asthma.

  7. Cytokines induce tight junction disassembly in airway cells via an EGFR-dependent MAPK/ERK1/2-pathway.

    Science.gov (United States)

    Petecchia, Loredana; Sabatini, Federica; Usai, Cesare; Caci, Emanuela; Varesio, Luigi; Rossi, Giovanni A

    2012-08-01

    Epithelial barrier permeability is altered in inflammatory respiratory disorders by a variety of noxious agents through modifications of the epithelial cell structure that possibly involve tight junction (TJ) organization. To evaluate in vitro whether pro-inflammatory cytokines involved in the pathogenesis of respiratory disorders could alter TJ organization and epithelial barrier integrity, and to characterize the signal transduction pathway involved Calu-3 airway epithelial cells were exposed to TNF-a, IL-4 and IFN-g to assess changes in: (a) TJ assembly, that is, occludin and zonula occludens (ZO)-1 expression and localization, evaluated by confocal microscopy; (b) apoptotic activity, quantified using terminal transferase deoxyuridine triphosphate nick-end labeling staining; (c) epithelial barrier integrity, detected as transmembrane electrical resistance and expressed as G(T) values; (d) epidermal growth factor receptor (EGFR)-dependent mitogenactivated protein (MAP) kinase (MAPK)/extracellular signal-regulated kinases (ERK)1/2 phosphorylation, assessed by western blotting. Exposure to cytokines for 48 h induced a noticeable downregulation of the TJ transmembrane proteins. The degree ZO-1 and occludin colocalization was 62±2% in control cultures and significantly decreased in the presence of TNF-a (47±3%), IL-4 (43±1%) and INF-g (35±3%). Although no apoptosis induction was detected following exposure to cytokines, changes in the epithelial barrier integrity were observed, with a significant enhancement in paracellular conductance. G(T) values were, respectively, 1.030±0.0, 1.300±0.04, 1.260±0.020 and 2.220±0.015 (mS/cm²)1000 in control cultures and in those exposed to TNF-a, IFN-g and IL-4. The involvement of EGFR-dependent MAPK/ERK1/2 signaling pathway in cytokine-induced damage was demonstrated by a significant increase in threonine/tyrosine phosphorylation of ERK1/2, already detectable after 5 min incubation. All these cytokine-induced changes were

  8. Lead Acetate Induces Epithelium-Dependent Contraction of Airway Smooth Muscle

    OpenAIRE

    , Ramadan B. Sopi; , Kemajl Bislimi; , Fetah Halili; , Mentor Sopjani; , Burim Neziri; , Muharrem Jakupi

    2016-01-01

    The effect of lead acetate on tracheal smooth muscle (TSM) of dog pups was investigated in this study. In addition we studied the role of epithelium and involvement of nitric oxide (NO) in counteracting the effects of lead acetate on TSM as well as the modifying effects of lead acetate on contractile responses of TSM to acetylcholine (ACh) . Tracheal rings were excised and placed in in vitro organ baths. In vitro administration of lead acetate in increasing concentrations(10-7–10-3 M) induced...

  9. Protective effect of Bifidobacterium infantis CGMCC313-2 on ovalbumin-induced airway asthma and β-lactoglobulin-induced intestinal food allergy mouse models

    Science.gov (United States)

    Liu, Meng-Yun; Yang, Zhen-Yu; Dai, Wen-Kui; Huang, Jian-Qiong; Li, Yin-Hu; Zhang, Juan; Qiu, Chuang-Zhao; Wei, Chun; Zhou, Qian; Sun, Xin; Feng, Xin; Li, Dong-Fang; Wang, He-Ping; Zheng, Yue-Jie

    2017-01-01

    AIM To determine whether oral administration of Bifidobacterium infantis CGMCC313-2 (B. infantis CGMCC313-2) inhibits allergen-induced airway inflammation and food allergies in a mouse model. METHODS Ovalbumin (OVA)-induced allergic asthma and β-lactoglobulin-induced food allergy mouse models were used in this study. Following oral administration of B. infantis CGMCC313-2 during or after allergen sensitization, histopathologic changes in the lung and intestine were evaluated by hematoxylin and eosin (HE) staining. In the allergic asthma mouse model, we evaluated the proportion of lung-infiltrating inflammatory cells. OVA-specific IgE and IgG1 levels in serum and cytokine levels in bronchoalveolar lavage fluid (BALF) were also assessed. In the food allergy mouse model, the levels of total IgE and cytokines in serum were measured. RESULTS Oral administration of B. infantis CGMCC313-2 during or after allergen sensitization suppressed allergic inflammation in lung and intestinal tissues, while the proportion of infiltrating inflammatory cells was significantly decreased in the BALF of allergic asthma mice. Moreover, B. infantis CGMCC313-2 decreased the serum levels of total IgE in food allergy mice, and reductions in IgE and IgG1 were also observed in OVA-induced allergic asthma mice. The expression of interleukin-4 (IL-4) and IL-13 in both serum and BALF was suppressed following the administration of B. infantis CGMCC313-2, while an effect on serum IL-10 levels was not observed. CONCLUSION B. infantis CGMCC313-2 inhibits the secretion of allergen-induced IgE, IL-4 and IL-13, and attenuates allergic inflammation.

  10. Airway epithelial NF-kappaB activation modulates asbestos-induced inflammation and mucin production in vivo.

    Science.gov (United States)

    Haegens, Astrid; Barrett, Trisha F; Gell, Joanna; Shukla, Arti; Macpherson, Maximilian; Vacek, Pamela; Poynter, Matthew E; Butnor, Kelly J; Janssen-Heininger, Yvonne M; Steele, Chad; Mossman, Brooke T

    2007-02-01

    To investigate the role of bronchiolar epithelial NF-kappaB activity in the development of inflammation and fibrogenesis in a murine model of asbestos inhalation, we used transgenic (Tg) mice expressing an IkappaBalpha mutant (IkappaBalphasr) resistant to phosphorylation-induced degradation and targeted to bronchial epithelium using the CC10 promoter. Sham and chrysotile asbestos-exposed CC10-IkappaBalphasr Tg(+) and Tg(-) mice were examined for altered epithelial cell proliferation and differentiation, cytokine profiles, lung inflammation, and fibrogenesis at 3, 9, and 40 days. KC, IL-6 and IL-1beta were increased (p < or = 0.05) in bronchoalveolar lavage fluid (BALF) from asbestos-exposed mice, but to a lesser extent (p < or = 0.05) in Tg(+) vs Tg(-) mice. Asbestos also caused increases in IL-4, MIP-1beta, and MCP-1 in BALF that were more elevated (p < or = 0.05) in Tg(+) mice at 9 days. Differential cell counts revealed eosinophils in BALF that increased (p < or = 0.05) in Tg(+) mice at 9 days, a time point corresponding with significantly increased numbers of bronchiolar epithelial cells staining positively for mucus production. At all time points, asbestos caused increased numbers of distal bronchiolar epithelial cells and peribronchiolar cells incorporating the proliferation marker, Ki-67. However, bronchiolar epithelial cell and interstitial cell labeling was diminished at 40 days (p < or = 0.05) in Tg(+) vs Tg(-) mice. Our findings demonstrate that airway epithelial NF-kappaB activity plays a role in orchestrating the inflammatory response as well as cell proliferation in response to asbestos.

  11. Potential of Inducible Nitric Oxide Synthase as a Therapeutic Target for Allergen-Induced Airway Hyperresponsiveness: A Critical Connection to Nitric Oxide Levels and PARP Activity

    Directory of Open Access Journals (Sweden)

    Salome’ V. Ibba

    2016-01-01

    Full Text Available Although expression of inducible NO synthase (iNOS in the lungs of asthmatics and associated nitrosative damage are established, iNOS failed as a therapeutic target for blocking airway hyperresponsiveness (AHR and inflammation in asthmatics. This dichotomy calls for better strategies with which the enzyme is adequately targeted. Here, we confirm iNOS expression in the asthmatic lung with concomitant protein nitration and poly(ADP-ribose polymerase (PARP activation. We show, for the first time, that iNOS is highly expressed in peripheral blood mononuclear cells (PBMCs of asthmatics with uncontrolled disease, which did not correspond to protein nitration. Selective iNOS inhibition with L-NIL protected against AHR upon acute, but not chronic, exposure to ovalbumin or house dust mite (HDM in mice. Supplementation of NO by nitrite administration significantly blocked AHR in chronically HDM-exposed mice that were treated with L-NIL. Protection against chronic HDM exposure-induced AHR by olaparib-mediated PARP inhibition may be associated with the partial but not the complete blockade of iNOS expression. Indeed, L-NIL administration prevented olaparib-mediated protection against AHR in chronically HDM-exposed mice. Our study suggests that the amount of iNOS and NO are critical determinants in the modulation of AHR by selective iNOS inhibitors and renews the potential of iNOS as a therapeutic target for asthma.

  12. Brainstem stimulation augments information integration in the cerebral cortex of desflurane-anesthetized rats.

    Science.gov (United States)

    Pillay, Siveshigan; Vizuete, Jeannette; Liu, Xiping; Juhasz, Gabor; Hudetz, Anthony G

    2014-01-01

    States of consciousness have been associated with information integration in the brain as modulated by anesthesia and the ascending arousal system. The present study was designed to test the hypothesis that electrical stimulation of the oral part of the pontine reticular nucleus (PnO) can augment information integration in the cerebral cortex of anesthetized rats. Extracellular unit activity and local field potentials were recorded in freely moving animals from parietal association (PtA) and secondary visual (V2) cortices via chronically implanted microwire arrays at three levels of anesthesia produced by desflurane: 3.5, 4.5, and 6.0% (where 4.5% corresponds to that critical for the loss of consciousness). Information integration was characterized by integration (multiinformation) and interaction entropy, estimated from the statistical distribution of coincident spike patterns. PnO stimulation elicited electrocortical activation as indicated by the reductions in δ- and θ-band powers at the intermediate level of anesthesia. PnO stimulation augmented integration from 1.13 ± 0.03 to 6.12 ± 1.98 × 10(3) bits and interaction entropy from 0.44 ± 0.11 to 2.18 ± 0.72 × 10(3) bits; these changes were most consistent in the PtA at all desflurane concentrations. Stimulation of the retina with discrete light flashes after PnO stimulation elicited an additional 166 ± 25 and 92 ± 12% increase in interaction entropy in V2 during light and intermediate levels. The results suggest that the PnO may modulate spontaneous ongoing and sensory stimulus-related cortical information integration under anesthesia.

  13. Brainstem stimulation augments information integration in the cerebral cortex of desflurane-anesthetized rats

    Directory of Open Access Journals (Sweden)

    Siveshigan ePillay

    2014-02-01

    Full Text Available States of consciousness have been associated with information integration in the brain as modulated by anesthesia and the ascending arousal system. The present study was designed to test the hypothesis that electrical stimulation of the oral part of the pontine reticular nucleus (PnO can augment information integration in the cerebral cortex of anesthetized rats. Extracellular unit activity and local field potentials were recorded in freely moving animals from parietal association (PtA and secondary visual (V2 cortices via chronically implanted microwire arrays at three levels of anesthesia produced by desflurane: 3.5%, 4.5%, and 6.0% (where 4.5% corresponds to that critical for the loss of consciousness. Information integration was characterized by integration (multiinformation and interaction entropy, estimated from the statistical distribution of coincident spike patterns. PnO stimulation elicited electrocortical activation as indicated by the reductions in δ- and θ-band powers at the intermediate level of anesthesia. PnO stimulation augmented integration from 1.13 ± 0.03 to 6.12 ± 1.98 x103 bits and interaction entropy from 0.44 ± 0.11 to 2.18 ± 0.72 x103 bits; these changes were most consistent in the PtA at all desflurane concentrations. Stimulation of the retina with discrete light flashes after PnO stimulation elicited an additional 166 ± 25 and 92 ± 12% increase in interaction entropy in V2 during light and intermediate levels. The results suggest that the PnO may modulate spontaneous ongoing and sensory stimulus-related cortical information integration under anesthesia.

  14. Restrained whole body plethysmography for measure of strain-specific and allergen-induced airway responsiveness in conscious mice.

    Science.gov (United States)

    Lofgren, Jennifer L S; Mazan, Melissa R; Ingenito, Edward P; Lascola, Kara; Seavey, Molly; Walsh, Ashley; Hoffman, Andrew M

    2006-11-01

    The mouse is the most extensively studied animal species in respiratory research, yet the technologies available to assess airway function in conscious mice are not universally accepted. We hypothesized that whole body plethysmography employing noninvasive restraint (RWBP) could be used to quantify specific airway resistance (sRaw-RWBP) and airway responsiveness in conscious mice. Methacholine responses were compared using sRaw-RWBP vs. airway resistance by the forced oscillation technique (Raw-FOT) in groups of C57, A/J, and BALB/c mice. sRaw-RWBP was also compared with sRaw derived from double chamber plethysmography (sRaw-DCP) in BALB/c. Finally, airway responsiveness following allergen challenge in BALB/c was measured using RWBP. sRaw-RWBP in C57, A/J, and BALB/c mice was 0.51 +/- 0.03, 0.68 +/- 0.03, and 0.63 +/- 0.05 cm/s, respectively. sRaw derived from Raw-FOT and functional residual capacity (Raw*functional residual capacity) was 0.095 cm/s, approximately one-fifth of sRaw-RWBP in C57 mice. The intra- and interanimal coefficients of variations were similar between sRaw-RWBP (6.8 and 20.1%) and Raw-FOT (3.4 and 20.1%, respectively). The order of airway responsiveness employing sRaw-RWBP was AJ > BALBc > C57 and for Raw-FOT was AJ > BALB/c = C57. There was no difference between the airway responsiveness assessed by RWBP vs. DCP; however, baseline sRaw-RWBP was significantly lower than sRaw-DCP. Allergen challenge caused a progressive decrease in the provocative concentration of methacholine that increased sRaw to 175% postsaline values based on sRaw-RWBP. In conclusion, the technique of RWBP was rapid, reproducible, and easy to perform. Airway responsiveness measured using RWBP, DCP, and FOT was equivalent. Allergen responses could be followed longitudinally, which may provide greater insight into the pathogenesis of chronic airway disease.

  15. Satratoxin-G from the black mold Stachybotrys chartarum induces rhinitis and apoptosis of olfactory sensory neurons in the nasal airways of rhesus monkeys.

    Science.gov (United States)

    Carey, Stephan A; Plopper, Charles G; Hyde, Dallas M; Islam, Zahidul; Pestka, James J; Harkema, Jack R

    2012-08-01

    Satratoxin-G (SG) is a trichothecene mycotoxin of Stachybotrys chartarum, the black mold suggested to contribute etiologically to illnesses associated with water-damaged buildings. We have reported that intranasal exposure to SG evokes apoptosis of olfactory sensory neurons (OSNs) and acute inflammation in the nose and brain of laboratory mice. To further assess the potential human risk of nasal airway injury and neurotoxicity, we developed a model of SG exposure in monkeys, whose nasal airways more closely resemble those of humans. Adult, male rhesus macaques received a single intranasal instillation of 20 µg SG (high dose, n = 3), or 5 µg SG daily for four days (repeated low dose, n = 3) in one nasal passage, and saline vehicle in the contralateral nasal passage. Nasal tissues were examined using light and electron microscopy and morphometric analysis. SG induced acute rhinitis, atrophy of the olfactory epithelium (OE), and apoptosis of OSNs in both groups. High-dose and repeated low-dose SG elicited a 13% and 66% reduction in OSN volume density, and a 14-fold and 24-fold increase in apoptotic cells of the OE, respectively. This model provides new insight into the potential risk of nasal airway injury and neurotoxicity caused by exposure to water-damaged buildings.

  16. Effects of four antitussives on airway neurogenic inflammation in a guinea pig model of chronic cough induced by cigarette smoke exposure.

    Science.gov (United States)

    Luo, Yu-long; Li, Pei-bo; Zhang, Chen-chen; Zheng, Yan-fang; Wang, Sheng; Nie, Yi-chu; Zhang, Ke-jian; Su, Wei-wei

    2013-12-01

    The effects of four antitussives, including codeine phosphate (CP), moguisteine, levodropropizine (LVDP) and naringin, on airway neurogenic inflammation and enhanced cough were investigated in guinea pig model of chronic cough. Guinea pigs were exposed to CS for 8 weeks. At the 7th and 8th week, the animals were treated with vehicle, CP (4.8 mg/kg), moguisteine (24 mg/kg), LVDP (14 mg/kg) and naringin (18.4 mg/kg) respectively. Then the cough and the time-enhanced pause area under the curve (Penh-AUC) during capsaicin challenge were recorded. The substance P (SP) content, NK-1 receptor expression and neutral endopeptidase (NEP) activity in lung were determined. Chronic CS exposure induced a bi-phase time course of cough responsiveness to capsaicin. Eight weeks of CS exposure significantly enhanced the airway neurogenic inflammation and cough response in guinea pigs. Two weeks of treatment with CP, moguisteine, LVDP or naringin effectively attenuated the chronic CS-exposure enhanced cough. Only naringin exerted significant effect on inhibiting Penh-AUC, SP content and NK-1 receptor expression, as well as preventing the declining of NEP activity in lung. Chronic CS-exposed guinea pig is suitable for studying chronic pathological cough, in which naringin is effective on inhibiting both airway neurogenic inflammation and enhanced cough.

  17. Cigarette smoke-induced collagen destruction; key to chronic neutrophilic airway inflammation?

    Directory of Open Access Journals (Sweden)

    Saskia A Overbeek

    Full Text Available BACKGROUND: Cigarette smoking induces inflammatory responses in all smokers and is the major risk factor for lung disease such as chronic obstructive pulmonary disease (COPD. In this progressive disease, chronic inflammation in the lung contributes to lung tissue destruction leading to the formation of chemotactic collagen fragments such as N-acetylated Proline-Glycine-Proline (N-ac-PGP. The generation of this tripeptide is mediated by a multistep pathway involving matrix metalloproteases (MMPs 8 and 9 and prolyl endopeptidase (PE. Here we investigated whether cigarette smoke extract (CSE stimulates human PMNs to breakdown whole matrix collagen leading to the generation of the chemotactic collagen fragment N-ac-PGP. METHODOLOGY/PRINCIPAL FINDINGS: Incubating PMNs with CSE led to the release of chemo-attractant CXCL8 and proteases MMP8 and MMP9. PMNs constitutively expressed PE activity as well as PE protein. Incubating CSE-primed PMNs with collagen resulted in collagen breakdown and in N-ac-PGP generation. Incubation of PMNs with the tripeptide N-ac-PGP resulted in the release of CXCL8, MMP8 and MMP9. Moreover, we tested whether PMNs from COPD patients are different from PMNs from healthy donors. Here we show that the intracellular basal PE activity of PMNs from COPD patients increased 25-fold compared to PMNs from healthy donors. Immunohistological staining of human lung tissue for PE showed that besides neutrophils, macrophages and epithelial cells express PE. CONCLUSIONS: This study indicates that neutrophils activated by cigarette smoke extract can breakdown collagen into N-ac-PGP and that this collagen fragment itself can activate neutrophils, which may lead in vivo to a self-propagating cycle of neutrophil infiltration, chronic inflammation and lung emphysema. MMP-, PE- or PGP-inhibitors can serve as an attractive therapeutic target and may open new avenues towards effective treatment of COPD.

  18. Ozone-induced inflammation in the lower airways of human subjects

    Energy Technology Data Exchange (ETDEWEB)

    Koren, H.S.; Devlin, R.B.; Graham, D.E.; Mann, R.; McGee, M.P.; Horstman, D.H.; Kozumbo, W.J.; Becker, S.; House, D.E.; McDonnell, W.F.

    1989-02-01

    Although ozone (O3) has been shown to induce inflammation in the lungs of animals, very little is known about its inflammatory effects on humans. In this study, 11 healthy nonsmoking men, 18 to 35 yr of age (mean, 25.4 +/- 3.5), were exposed once to 0.4 ppm O3 and once to filtered air for 2 h with intermittent exercise. Eighteen hours later, bronchoalveolar lavage (BAL) was performed and the cells and fluid were analyzed for various indicators of inflammation. There was an 8.2-fold increase in the percentage of polymorphonuclear leukocytes (PMN) in the total cell population, and a small but significant decrease in the percentage of macrophages after exposure to O3. Immunoreactive neutrophil elastase often associated with inflammation and lung damage increased by 3.8-fold in the fluid while its activity increased 20.6-fold in the lavaged cells. A 2-fold increase in the levels of protein, albumin, and IgG suggested increased vascular permeability of the lung. Several biochemical markers that could act as chemotactic or regulatory factors in an inflammatory response were examined in the BAL fluid (BALF). The level of complement fragment C3 alpha was increased by 1.7-fold. The chemotactic leukotriene B4 was unchanged while prostaglandin E2 increased 2-fold. In contrast, three enzyme systems of phagocytes with potentially damaging effects on tissues and microbes, namely, NADPH-oxidase and the lysosomal enzymes acid phosphatase and beta-glucuronidase, were increased neither in the lavaged fluid nor cells. In addition, the amounts of fibrogenic-related molecules were assessed in BALF.

  19. Airway inflammation and IgE production induced by dust mite allergen-specific memory/effector Th2 cell line can be effectively attenuated by IL-35.

    Science.gov (United States)

    Huang, Chiung-Hui; Loo, Evelyn Xiu-Ling; Kuo, I-Chun; Soh, Gim Hooi; Goh, Denise Li-Meng; Lee, Bee Wah; Chua, Kaw Yan

    2011-07-01

    CD4(+) memory/effector T cells play a central role in orchestrating the rapid and robust immune responses upon re-encounter with specific Ags. However, the immunologic mechanism(s) underlying these responses are still not fully understood. To investigate this, we generated an allergen (major house dust mite allergen, Blo t 5)-specific murine Th2 cell line that secreted IL-4, IL-5, IL-10, and IL-13, but not IL-9 or TNF-α, upon activation by the cognate Ag. These cells also exhibited CD44(high)CD62L(-) and CD127(+) (IL-7Rα(+)) phenotypes, which are characteristics of memory/effector T cells. Experiments involving adoptive transfer of this Th2 cell line in mice, followed by three intranasal challenges with Blo t 5, induced a dexamethasone-sensitive eosinophilic airway inflammation. This was accompanied by elevation of Th2 cytokines and CC- and CXC-motif chemokines, as well as recruitment of lymphocytes and polymorphic mononuclear cells into the lungs. Moreover, Blo t 5-specific IgE was detected 4 d after the last intranasal challenge, whereas elevation of Blo t 5-specific IgG1 was found at week two. Finally, pulmonary delivery of the pVAX-IL-35 DNA construct effectively downregulated Blo t 5-specific allergic airway inflammation, and i.m. injection of pVAX-IL-35 led to long-lasting suppression of circulating Blo t 5-specific and total IgE. This model provides a robust research tool to elucidate the immunopathogenic role of memory/effector Th2 cells in allergic airway inflammation. Our results suggested that IL-35 could be a potential therapeutic target for allergic asthma through its attenuating effects on allergen-specific CD4(+) memory/effector Th2 cell-mediated airway inflammation.

  20. Development of a Physiologically Based Pharmacokinetic Model for the Anesthetics Halothane, Isoflurane, and Desflurane in the Pig (SUS SCROFA)

    Science.gov (United States)

    1999-08-01

    HALOTHANE, ISOFLURANE, AND DESFLURANE IN THE PIG ( SUS SCROFA ) / Allen Vinegar MANTECH-GEO CENTER JOINT VENTURE PO BOX 31009 ~ DAYTON, OH 45437-0009...Pharmacokinetic Model for the Anesthetics Contract F41624-96-C-9010 Halothane, Isoflurane, and Desfiurane in the Pig ( Sus Scrofa ) PE 62202F PR 7757 6. AUTHOR(S) TA...PFA) " CA Figure I - Physiologicallly Based Pharmacokinetic Model of the Pig ( Sus scrofa ). Abbreviations: CA, arterial concentration; CX, exhaled

  1. [Concentration-dependent changes in the latency and amplitude of somatosensory-evoked potentials by desflurane, isoflurane and sevoflurane].

    Science.gov (United States)

    Rehberg, B; Rüschner, R; Fischer, M; Ebeling, B J; Hoeft, A

    1998-07-01

    Comparison of the influence of desflurane, isoflurane, and sevoflurane on the parameters of cortical somatosensory evoked potentials (SEP). A total of 41 patients were randomly allocated to either the isoflurane, desflurane or sevoflurane group. Following induction with propofol and intubation, concentration of the volatile anaesthetic was kept constant at 1.3, 1.0, and 0.7 MAC for 15 minutes each in randomised sequences. No opioids or N2O were used. Cortical somatosensory evoked potentials were recorded following median nerve stimulation at the wrist with 1.5 times motor threshold current. SEP were evaluated for latencies of peak N20 and P25 as well as peak-to-peak amplitude N20P25. Measurements at the end of the 15 minute equilibration intervals were compared by analysis of variance for repeated measurements. Latencies and the logarithm of the amplitudes were assumed to be normally distributed. SEP could be recorded in all patients and at all concentrations. Latency of cortical SEP increased with anaesthetic concentration in a linear manner. No differences in latency increase were found between the three anaesthetics (ANOVA). In contrast, the decrease in amplitude with increasing anaesthetic concentration was non-linear. It was large from control to 0.7 MAC, but small in the range between 0.7 and 1.3 MAC. Amplitude reduction was larger with isoflurane than with sevoflurane or desflurane. 1) Sevoflurane and desflurane are better suited for anaesthetic management during intraoperative electrophysiological monitoring than isoflurane, because SEP amplitudes are better preserved. 2) SEP amplitude is less altered by changing anaesthetic concentrations in the concentration range from 0.7 to 1.3 MAC than SEP latency.

  2. Serum- and glucocorticoid-induced protein kinase 1 (SGK1) increases the cystic fibrosis transmembrane conductance regulator (CFTR) in airway epithelial cells by phosphorylating Shank2E protein.

    Science.gov (United States)

    Koeppen, Katja; Coutermarsh, Bonita A; Madden, Dean R; Stanton, Bruce A

    2014-06-13

    The glucocorticoid dexamethasone increases cystic fibrosis transmembrane conductance regulator (CFTR) abundance in human airway epithelial cells by a mechanism that requires serum- and glucocorticoid-induced protein kinase 1 (SGK1) activity. The goal of this study was to determine whether SGK1 increases CFTR abundance by phosphorylating Shank2E, a PDZ domain protein that contains two SGK1 phosphorylation consensus sites. We found that SGK1 phosphorylates Shank2E as well as a peptide containing the first SGK1 consensus motif of Shank2E. The dexamethasone-induced increase in CFTR abundance was diminished by overexpression of a dominant-negative Shank2E in which the SGK1 phosphorylation sites had been mutated. siRNA-mediated reduction of Shank2E also reduced the dexamethasone-induced increase in CFTR abundance. Taken together, these data demonstrate that the glucocorticoid-induced increase in CFTR abundance requires phosphorylation of Shank2E at an SGK1 consensus site.

  3. p110γ/δ Double-Deficiency Induces Eosinophilia and IgE Production but Protects from OVA-Induced Airway Inflammation.

    Science.gov (United States)

    Mothes, Benedikt; Bucher, Kirsten; Ammon-Treiber, Susanne; Schwab, Matthias; Piekorz, Roland P; Hirsch, Emilio; Nürnberg, Bernd; Beer-Hammer, Sandra

    2016-01-01

    The catalytical isoforms p110γ and p110δ of phosphatidylinositide 3-kinase γ (PI3Kγ) and PI3Kδ play an important role in the pathogenesis of asthma. Two key elements in allergic asthma are increased levels of eosinophils and IgE. Dual pharmacological inhibition of p110γ and p110δ reduces asthma-associated eosinophilic lung infiltration and ameliorates disease symptoms, whereas the absence of enzymatic activity in p110γKOδD910A mice increases IgE and basal eosinophil counts. This suggests that long-term inhibition of p110γ and p110δ might exacerbate asthma. Here, we analysed mice genetically deficient for both catalytical subunits (p110γ/δ-/-) and determined basal IgE and eosinophil levels and the immune response to ovalbumin-induced asthma. Serum concentrations of IgE, IL-5 and eosinophil numbers were significantly increased in p110γ/δ-/- mice compared to single knock-out and wildtype mice. However, p110γ/δ-/- mice were protected against OVA-induced infiltration of eosinophils, neutrophils, T and B cells into lung tissue and bronchoalveolar space. Moreover, p110γ/δ-/- mice, but not single knock-out mice, showed a reduced bronchial hyperresponsiveness. We conclude that increased levels of eosinophils and IgE in p110γ/δ-/- mice do not abolish the protective effect of p110γ/δ-deficiency against OVA-induced allergic airway inflammation.

  4. Effect of a single dose of esmolol on the bispectral index to endotracheal intubation during desflurane anesthesia.

    Science.gov (United States)

    Choi, Eun Mi; Min, Kyeong Tae; Lee, Jeong Rim; Lee, Tai Kyung; Choi, Seung Ho

    2013-05-01

    In this prospective, randomized, double-blind, placebo-controlled trial, we investigated the effect of a single dose of esmolol on the bispectral index (BIS) to endotracheal intubation during desflurane anesthesia. After induction of anesthesia, 60 patients were mask-ventilated with desflurane (end-tidal 1 minimum alveolar concentration) for 5 min and then received either normal saline, esmolol 0.5 or 1 mg/kg, 1 min prior to intubation (control, esmolol-0.5 and esmolol-1 groups, n = 20/group). BIS, mean arterial pressure, and heart rate were measured prior to anesthesia induction and esmolol administration, immediately preceding intubation (time point 0), and every minute for 5 min after intubation (time point 1 to 5). At time point 0, 1 and 5, 5 ml of arterial blood was taken to measure plasma concentrations of norepinephrine and epinephrine. BIS increased significantly at 1 min after intubation when compared with pre-intubation values in all groups. Both mean arterial pressure and heart rate increased significantly 1 min after intubation when compared with preintubation values for all groups. Plasma epinephrine concentrations did not increase significantly after tracheal intubation in any of the groups. Norepinephrine increased at 1 min after intubation when compared with the preintubation values in the esmolol groups (P endotracheal intubation during desflurane anesthesia.

  5. A new removable airway stent

    Directory of Open Access Journals (Sweden)

    Tore Amundsen

    2016-09-01

    Full Text Available Background: Malignant airway obstruction is a feared complication and will most probably occur more frequently in the future because of increasing cancer incidence and increased life expectancy in cancer patients. Minimal invasive treatment using airway stents represents a meaningful and life-saving palliation. We present a new removable airway stent for improved individualised treatment. Methods: To our knowledge, the new airway stent is the world's first knitted and uncovered self-expanding metal stent, which can unravel and be completely removed. In an in vivo model using two anaesthetised and spontaneously breathing pigs, we deployed and subsequently removed the stents by unravelling the device. The procedures were executed by flexible bronchoscopy in an acute and a chronic setting – a ‘proof-of-principle’ study. Results: The new stent was easily and accurately deployed in the central airways, and it remained fixed in its original position. It was easy to unravel and completely remove from the airways without clinically significant complications. During the presence of the stent in the chronic study, granulation tissue was induced. This tissue disappeared spontaneously with the removal. Conclusions: The new removable stent functioned according to its purpose and unravelled easily, and it was completely removed without significant technical or medical complications. Induced granulation tissue disappeared spontaneously. Further studies on animals and humans are needed to define its optimal indications and future use.

  6. Role of signal transducer and activator of transcription 1 in murine allergen-induced airway remodeling and exacerbation by carbon nanotubes.

    Science.gov (United States)

    Thompson, Elizabeth A; Sayers, Brian C; Glista-Baker, Ellen E; Shipkowski, Kelly A; Ihrie, Mark D; Duke, Katherine S; Taylor, Alexia J; Bonner, James C

    2015-11-01

    Asthma is characterized by a T helper type 2 phenotype and by chronic allergen-induced airway inflammation (AAI). Environmental exposure to air pollution ultrafine particles (i.e., nanoparticles) exacerbates AAI, and a concern is possible exacerbation posed by engineered nanoparticles generated by emerging nanotechnologies. Signal transducer and activator of transcription (STAT) 1 is a transcription factor that maintains T helper type 1 cell development. However, the role of STAT1 in regulating AAI or exacerbation by nanoparticles has not been explored. In this study, mice with whole-body knockout of the Stat1 gene (Stat1(-/-)) or wild-type (WT) mice were sensitized to ovalbumin (OVA) allergen and then exposed to multiwalled carbon nanotubes (MWCNTs) by oropharygneal aspiration. In Stat1(-/-) and WT mice, OVA increased eosinophils in bronchoalveolar lavage fluid, whereas MWCNTs increased neutrophils. Interestingly, OVA sensitization prevented MWCNT-induced neutrophilia and caused only eosinophilic inflammation. Stat1(-/-) mice displayed increased IL-13 in bronchoalveolar lavage fluid at 1 day compared with WT mice after treatment with OVA or OVA and MWCNTs. At 21 days, the lungs of OVA-sensitized Stat1(-/-) mice displayed increased eosinophilia, goblet cell hyperplasia, airway fibrosis, and subepithelial apoptosis. MWCNTs further increased OVA-induced goblet cell hyperplasia, airway fibrosis, and apoptosis in Stat1(-/-) mice at 21 days. These changes corresponded to increased levels of profibrogenic mediators (transforming growth factor-β1, TNF-α, osteopontin) but decreased IL-10 in Stat1(-/-) mice. Finally, fibroblasts isolated from the lungs of Stat1(-/-) mice produced significantly more collagen mRNA and protein in response to transforming growth factor-β1 compared with WT lung fibroblasts. Our results support a protective role for STAT1 in chronic AAI and exacerbation of remodeling caused by MWCNTs.

  7. Bone marrow cell derived arginase I is the major source of allergen-induced lung arginase but is not required for airway hyperresponsiveness, remodeling and lung inflammatory responses in mice

    Directory of Open Access Journals (Sweden)

    Rothenberg Marc E

    2009-06-01

    Full Text Available Abstract Background Arginase is significantly upregulated in the lungs in murine models of asthma, as well as in human asthma, but its role in allergic airway inflammation has not been fully elucidated in mice. Results In order to test the hypothesis that arginase has a role in allergic airway inflammation we generated arginase I-deficient bone marrow (BM chimeric mice. Following transfer of arginase I-deficient BM into irradiated recipient mice, arginase I expression was not required for hematopoietic reconstitution and baseline immunity. Arginase I deficiency in bone marrow-derived cells decreased allergen-induced lung arginase by 85.8 ± 5.6%. In contrast, arginase II-deficient mice had increased lung arginase activity following allergen challenge to a similar level to wild type mice. BM-derived arginase I was not required for allergen-elicited sensitization, recruitment of inflammatory cells in the lung, and proliferation of cells. Furthermore, allergen-induced airway hyperresponsiveness and collagen deposition were similar in arginase-deficient and wild type mice. Additionally, arginase II-deficient mice respond similarly to their control wild type mice with allergen-induced inflammation, airway hyperresponsiveness, proliferation and collagen deposition. Conclusion Bone marrow cell derived arginase I is the predominant source of allergen-induced lung arginase but is not required for allergen-induced inflammation, airway hyperresponsiveness or collagen deposition.

  8. The glutathione-S-transferase Mu 1 null genotype modulates ozone-induced airway inflammation in humans*

    Science.gov (United States)

    Background: The Glutathione-S-Transferase Mu 1 null genotype has been reported to be a risk factor for acute respiratory disease associated with increases in ambient air ozone. Ozone is known to cause an immediate decrease in lung function and increased airway inflammation. Howev...

  9. Proteases from Aspergillus fumigatus induce release of proinflammatory cytokines and cell detachment in airway epithelial cell lines

    NARCIS (Netherlands)

    Tomee, JFC; Hiemstra, PS; Kauffman, HF

    1997-01-01

    Aspergillus fumigatus is a pathogen causing; diverse respiratory disorders, Several studies have suggested that fungal proteases may play a role in the pathogenicity of fungi, Since the airways are the most common route for entry of. A, fumigatus, this study focused on the ability of fungal protease

  10. Tedizolid inhibits MUC5AC production induced by methicillin-resistant Staphylococcus aureus in human airway epithelial cells.

    Science.gov (United States)

    Takeda, Kazuaki; Kaku, Norihito; Morinaga, Yoshitomo; Kosai, Kosuke; Uno, Naoki; Imamura, Yoshifumi; Hasegawa, Hiroo; Miyazaki, Taiga; Izumikawa, Koichi; Mukae, Hiroshi; Yanagihara, Katsunori

    2017-09-01

    The innate immune system plays an important role in early immunity against respiratory tract infection. Although airway epithelial cells produce mucus to eliminate pathogens and irritants, hypersecretion of mucus is harmful for the host as it may cause airway obstruction and inhibit influx of antimicrobial agents. It has been reported that several antimicrobial agents have an immunomodulatory effect in vitro and in vivo, but little is known about whether tedizolid, a novel oxazolidinone, can modulate immune responses. In this study, we evaluated whether tedizolid can suppress MUC5AC production in human airway epithelial cells stimulated by methicillin-resistant Staphylococcus aureus (MRSA). Compared with the control, tedizolid significantly inhibited MUC5AC protein production and mRNA overexpression at concentrations of both 2 and 10 μg/mL (representative of trough and peak concentrations in human epithelial lining fluid). Among the mitogen-activated protein kinase inhibitors tested, only extracellular signal-regulated protein kinase 1/2 (ERK1/2) phosphorylation was inhibited by tedizolid as indicated by western blot analysis. These results indicate that tedizolid inhibits the overproduction of MUC5AC protein by inhibiting phosphorylation of ERK1/2. This study revealed that tedizolid suppresses excessive mucin production in human airway epithelial cells. The immunomodulatory effect of tedizolid may improve outcomes in patients with severe respiratory infectious diseases caused by MRSA. Copyright © 2017 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  11. The glutathione-S-transferase Mu 1 null genotype modulates ozone-induced airway inflammation in humans*

    Science.gov (United States)

    Background: The Glutathione-S-Transferase Mu 1 null genotype has been reported to be a risk factor for acute respiratory disease associated with increases in ambient air ozone. Ozone is known to cause an immediate decrease in lung function and increased airway inflammation. Howev...

  12. Zinc sulfate inhibited inflammation of Der p2-induced airway smooth muscle cells by suppressing ERK1/2 and NF-κB phosphorylation.

    Science.gov (United States)

    Shih, Chia-Ju; Chiou, Ya-Ling

    2013-06-01

    Inflammation of airway smooth muscle cells (ASMCs) is believed to be important in causing airway hyperresponsiveness. However, zinc has been reported to be implicated in many kinds of cell inflammation. Little is known about the effect of zinc treatment on Der p2 (group II Dermatophagoides pteronyssinus)-induced inflammation from ASMCs. This study investigated effects and mechanisms of zinc in Der p2-treated ASMCs. Der p2-treated primary ASMCs were cultured with various concentrations of zinc sulfate (ZnSO₄) 6 μM, 12 μM, 24 μM, and 96 μM. The proteins and mRNAs of cytokines in ASMCs were examined by ELISA and real-time PCR. Intracellular zinc was stained with Zinquin fluorescence. The cell signaling protein expression was detected by Western blot. Der p2 was used to induce interleukin (IL)-6, IL-8, IL-1, and monocyte chemotactic protein-1 production of ASMCs. However, we found that 24 μM ZnSO₄ reduced these inflammatory mediators production of Der p2-treated primary ASMCs. Der p2-induced extracellular signal-regulated kinases (ERK) and nuclear factor-kappa B (NF-κB) phosphorylation were suppressed by supplementation of 24 μM ZnSO₄. Zinc is an anti-inflammatory agent that reduces inflammation of Der p2-treated ASMCs through the suppression of the ERK and NF-κB pathway. The results may be helpful for the development of effective treatments.

  13. Sub-chronic inhalation of high concentrations of manganese sulfate induces lower airway pathology in rhesus monkeys

    Directory of Open Access Journals (Sweden)

    Wong Brian A

    2005-10-01

    Full Text Available Abstract Background Neurotoxicity and pulmonary dysfunction are well-recognized problems associated with prolonged human exposure to high concentrations of airborne manganese. Surprisingly, histological characterization of pulmonary responses induced by manganese remains incomplete. The primary objective of this study was to characterize histologic changes in the monkey respiratory tract following manganese inhalation. Methods Subchronic (6 hr/day, 5 days/week inhalation exposure of young male rhesus monkeys to manganese sulfate was performed. One cohort of monkeys (n = 4–6 animals/exposure concentration was exposed to air or manganese sulfate at 0.06, 0.3, or 1.5 mg Mn/m3 for 65 exposure days. Another eight monkeys were exposed to manganese sulfate at 1.5 mg Mn/m3 for 65 exposure days and held for 45 or 90 days before evaluation. A second cohort (n = 4 monkeys per time point was exposed to manganese sulfate at 1.5 mg Mn/m3 and evaluated after 15 or 33 exposure days. Evaluations included measurement of lung manganese concentrations and evaluation of respiratory histologic changes. Tissue manganese concentrations were compared for the exposure and control groups by tests for homogeneity of variance, analysis of variance, followed by Dunnett's multiple comparison. Histopathological findings were evaluated using a Pearson's Chi-Square test. Results Animals exposed to manganese sulfate at ≥0.3 mg Mn/m3 for 65 days had increased lung manganese concentrations. Exposure to manganese sulfate at 1.5 mg Mn/m3 for ≥15 exposure days resulted in increased lung manganese concentrations, mild subacute bronchiolitis, alveolar duct inflammation, and proliferation of bronchus-associated lymphoid tissue. Bronchiolitis and alveolar duct inflammatory changes were absent 45 days post-exposure, suggesting that these lesions are reversible upon cessation of subchronic high-dose manganese exposure. Conclusion High-dose subchronic manganese sulfate inhalation is

  14. Comparison of the effects of inhalational anesthesia with desflurane and total intravenous anesthesia on cardiac biomarkers after aortic valve replacement

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    Poonam Malhotra Kapoor

    2015-01-01

    Full Text Available Objective (s: The aim of this study was to compare the effects of using inhalational anesthesia with desflurane with that of a total intravenous (iv anesthetic technique using midazolam-fentanyl-propofol on the release of cardiac biomarkers after aortic valve replacement (AVR for aortic stenosis (AS. The specific objectives included (a determination of the levels of ischemia-modified albumin (IMA and cardiac troponin I (cTnI as markers of myocardial injury, (b effect on mortality, morbidity, duration of mechanical ventilation, length of Intensive Care Unit (ICU and hospital stay, incidence of arrhythmias, pacing, cardioversion, urine output, and serum creatinine. Methodology and Design: Prospective randomized clinical study. Setting: Operation room of a cardiac surgery center of a tertiary teaching hospital. Participants: Seventy-six patients in New York Heart Association classification II to III presenting electively for AVR for severe symptomatic AS. Interventions: Patients included in the study were randomized into two groups and subjected to either a desflurane-fentanyl based technique or total IV anesthesia (TIVA. Blood samples were drawn at preordained intervals to determine the levels of IMA, cTnI, and serum creatinine. Measurements and Main Results: The IMA and cTnI levels were not found to be significantly different between both the study groups. Patients in the desflurane group were found to had significantly lower ICU and hospital stays and duration of postoperative mechanical ventilation as compared to those in the TIVA group. There was no difference found in mean heart rate, urine output, serum creatinine, incidence of arrhythmias, need for cardioversion, and 30-day mortality between both groups. The patients in the TIVA group had higher mean arterial pressures on weaning off cardiopulmonary bypass as well as postoperatively in the ICU and recorded lower inotrope usage. Conclusion: The result of our study remains ambiguous regarding

  15. Th1 cytokine-induced syndecan-4 shedding by airway smooth muscle cells is dependent on mitogen-activated protein kinases.

    Science.gov (United States)

    Tan, Xiahui; Khalil, Najwa; Tesarik, Candice; Vanapalli, Karunasri; Yaputra, Viki; Alkhouri, Hatem; Oliver, Brian G G; Armour, Carol L; Hughes, J Margaret

    2012-04-01

    In asthma, airway smooth muscle (ASM) chemokine secretion can induce mast cell recruitment into the airways. The functions of the mast cell chemoattractant CXCL10, and other chemokines, are regulated by binding to heparan sulphates such as syndecan-4. This study is the first demonstration that airway smooth muscle cells (ASMC) from people with and without asthma express and shed syndecan-4 under basal conditions. Syndecan-4 shedding was enhanced by stimulation for 24 h with the Th1 cytokines interleukin-1β (IL-1β) or tumor necrosis factor-α (TNF-α), but not interferon-γ (IFNγ), nor the Th2 cytokines IL-4 and IL-13. ASMC stimulation with IL-1β, TNF-α, and IFNγ (cytomix) induced the highest level of syndecan-4 shedding. Nonasthmatic and asthmatic ASM cell-associated syndecan-4 protein expression was also increased by TNF-α or cytomix at 4-8 h, with the highest levels detected in cytomix-stimulated asthmatic cells. Cell-associated syndecan-4 levels were decreased by 24 h, whereas shedding remained elevated at 24 h, consistent with newly synthesized syndecan-4 being shed. Inhibition of ASMC matrix metalloproteinase-2 did not prevent syndecan-4 shedding, whereas inhibition of ERK MAPK activation reduced shedding from cytomix-stimulated ASMC. Although ERK inhibition had no effect on syndecan-4 mRNA levels stimulated by cytomix, it did cause an increase in cell-associated syndecan-4 levels, consistent with the shedding being inhibited. In conclusion, ASMC produce and shed syndecan-4 and although this is increased by the Th1 cytokines, the MAPK ERK only regulates shedding. ASMC syndecan-4 production during Th1 inflammatory conditions may regulate chemokine activity and mast cell recruitment to the ASM in asthma.

  16. Lipocalin2 protects against airway inflammation and hyperresponsiveness in a murine model of allergic airway disease

    DEFF Research Database (Denmark)

    Dittrich, A M; Krokowski, M; Meyer, H-A;

    2010-01-01

    Allergen-induced bronchial asthma is a chronic airway disease that involves the interplay of various genes with environmental factors triggering different inflammatory pathways.......Allergen-induced bronchial asthma is a chronic airway disease that involves the interplay of various genes with environmental factors triggering different inflammatory pathways....

  17. PI3K-delta mediates double-stranded RNA-induced upregulation of B7-H1 in BEAS-2B airway epithelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Kan-o, Keiko [Research Institute for Diseases of the Chest, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582 (Japan); Matsumoto, Koichiro, E-mail: koichi@kokyu.med.kyushu-u.ac.jp [Research Institute for Diseases of the Chest, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582 (Japan); Asai-Tajiri, Yukari; Fukuyama, Satoru; Hamano, Saaka; Seki, Nanae; Nakanishi, Yoichi [Research Institute for Diseases of the Chest, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582 (Japan); Inoue, Hiromasa [Research Institute for Diseases of the Chest, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582 (Japan); Department of Pulmonary Medicine, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima 890-8520 (Japan)

    2013-05-31

    Highlights: •Double-stranded RNA upregulates B7-H1 on BEAS-2B airway epithelial cells. •The upregulation of B7-H1 is attenuated by inhibition of PI3Kδ isoform. •PI3Kδ-mediated upregulation of B7-H1 is independent of NF-κB activation. •Inhibition of PI3Kδ may prevent persistent viral infection induced by B7-H1. -- Abstract: Airway viral infection disturbs the health-related quality of life. B7-H1 (also known as PD-L1) is a coinhibitory molecule associated with the escape of viruses from the mucosal immunity, leading to persistent infection. Most respiratory viruses generate double-stranded (ds) RNA during replication. The stimulation of cultured airway epithelial cells with an analog of viral dsRNA, polyinosinic-polycytidylic acid (poly IC) upregulates the expression of B7-H1 via activation of the nuclear factor κB(NF-κB). The mechanism of upregulation was investigated in association with phosphatidylinositol 3-kinases (PI3Ks). Poly IC-induced upregulation of B7-H1 was profoundly suppressed by a pan-PI3K inhibitor and partially by an inhibitor or a small interfering (si)RNA for PI3Kδ in BEAS-2B cells. Similar results were observed in the respiratory syncytial virus-infected cells. The expression of p110δ was detected by Western blot and suppressed by pretreatment with PI3Kδ siRNA. The activation of PI3Kδ is typically induced by oxidative stress. The generation of reactive oxygen species was increased by poly IC. Poly IC-induced upregulation of B7-H1 was attenuated by N-acetyl-L-cysteine, an antioxidant, or by oxypurinol, an inhibitor of xanthine oxidase. Poly IC-induced activation of NF-κB was suppressed by a pan-PI3K inhibitor but not by a PI3Kδ inhibitor. These results suggest that PI3Kδ mediates dsRNA-induced upregulation of B7-H1 without affecting the activation of NF-κB.

  18. Entropy-guided end-tidal desflurane concentration during living donor liver transplantation

    Directory of Open Access Journals (Sweden)

    Ashraf S Hasanin

    2013-01-01

    Full Text Available Background: The three phases of living donor liver transplantation (LDLT represent different liver conditions. The aim is to study the required end-tidal desflurane concentration (ET-Des guided with entropy monitoring for the depth of anesthesia. Methods: After the Ethics and Research Committee approval, 40 patients were included in this prospective study. Anesthesia was maintained with Desflurane-O2-air. State entropy (SE and Response entropy (RE were kept between 40 and 60. Results: Age and Model for End-stage Liver Disease (MELD score were 45±10 years and 15.43±3.92, respectively. ET-Des were significantly lower in the anhepatic phase (2.8±0.4% than in the pre-anhepatic and neohepatic phases (3.3±0.3%, 3.47±0.3%, respectively, P 0.05. Total operative time was 651±88 minutes, and for each phase it was 276±11, 195±55, and 191±24 minutes, respectively. Significant changes were found in hemoglobin g/dl and hematocrit % between the three phases (10.28±1.5, 30.48±4.3, (9.45±1.34, 28.36±4.1, and (8.88±1.1, 26.63±3.5, P<0.05. The heart rate and mean blood pressures were stable despite the cardiac index demonstrated a significant reduction during the anhepatic phase (2.99±0.22 when compared to the pre-anhepatic and neohepatic phases (3.60±0.29 and (4.72±0.32, respectively, ( P<0.05. There was a significant correlation between CI and ET-Des% (r=0.604, P<0.05. Conclusion: Inhalational anesthetic requirements differed from one phase to another during LDLT, with requirements being the least during the anhepatic phase. Monitoring of the anesthesia depth was required, to avoid excess administration, which could compromise the hemodynamics before the critical time of reperfusion.

  19. Intradermal cytosine-phosphate-guanosine treatment reduces lung inflammation but induces IFN-γ-mediated airway hyperreactivity in a murine model of natural rubber latex allergy.

    Science.gov (United States)

    Haapakoski, Rita; Karisola, Piia; Fyhrquist, Nanna; Savinko, Terhi; Wolff, Henrik; Turjanmaa, Kristiina; Palosuo, Timo; Reunala, Timo; Lauerma, Antti; Alenius, Harri

    2011-05-01

    Asthma and other allergic diseases are continuously increasing, causing considerable economic and sociologic burden to society. The hygiene hypothesis proposes that lack of microbial T helper (Th) 1-like stimulation during early childhood leads to increased Th2-driven allergic disorders later in life. Immunostimulatory cytosine-phosphate-guanosine (CpG)-oligodeoxynucleotide motifs are candidate molecules for immunotherapeutic studies, as they have been shown to shift the Th2 response toward the Th1 direction and reduce allergic symptoms. Using natural rubber latex (NRL)-induced murine model of asthma, we demonstrated that intradermal CpG administration with allergen reduced pulmonary eosinophilia, mucus production, and Th2-type cytokines, but unexpectedly induced airway hyperreactivity (AHR) to inhaled methacholine, one of the hallmarks of asthma. We found that induction in AHR was dependent on STAT4, but independent of STAT6 signaling. CpG treatment increased production of IFN-γ in the airways and shifted the ratio of CD4(+):CD8(+) T cells toward CD8(+) dominance. By blocking soluble IFN-γ with neutralizing antibody, AHR diminished and the CD4(+):CD8(+) ratio returned to CD4(+) dominance. These results indicate that increased production of IFN-γ in the lungs may lead to severe side effects, such as enhancement of bronchial hyperreactivity to inhaled allergen. This finding should be taken into consideration when planning prophylaxis treatment of asthma with intradermal CpG injections.

  20. Mechanisms of aldehyde-induced bronchial reactivity: Role of airway epithelium. Research report, July 1986-January 1991

    Energy Technology Data Exchange (ETDEWEB)

    Leikauf, G.D.

    1991-01-01

    The purpose of the study was to determine whether exposures to environmentally relevant concentrations of two aldehydes of low molecular weight were associated with impaired airway function. Specifically, the study addressed questions of the relative irritant potency of formaldehyde and acrolein on the induction of increased bronchial reactivity to acetylcholine in guinea pigs. The relationship of bronchial reactivity to epithelial damage and inflammation were also examined after both in vivo and in vitro exposures.

  1. Bronchoconstriction and airway biology : potential impact and therapeutic opportunities

    NARCIS (Netherlands)

    Gosens, Reinoud; Grainge, Chris

    2015-01-01

    Recent work has demonstrated that mechanical forces occurring in the airway as a consequence of bronchoconstriction are sufficient to not only induce symptoms but also influence airway biology. Animal and human in vitro and in vivo work demonstrates that the airways are structurally and functionally

  2. Myocardial protection during off pump coronary artery bypass surgery: A comparison of inhalational anesthesia with sevoflurane or desflurane and total intravenous anesthesia

    Directory of Open Access Journals (Sweden)

    Sharadaprasad Suryaprakash

    2013-01-01

    Full Text Available Aims and Objectives: The objective of the study was to evaluate the myocardial protective effect of volatile agents-sevoflurane and desflurane versus total intravenous anesthesia (TIVA with propofol in offpump coronary artery bypass surgery (OPCAB by measuring cardiac troponin-T (cTnT as a marker of myocardial cell death. Materials and Methods: The study was conducted on 139 patients scheduled to undergo elective OPCAB surgery. The patients were randomly allocated to receive anesthesia with sevoflurane, desflurane or TIVA with propofol. The cTnT levels were measured preoperatively, at arrival in postoperative intensive care unit, at 8, 24, 48 and 96 hours thereafter. Results: The changes in cTnT levels at all time intervals were comparable in the three groups. Conclusion: The study did not reveal any difference in myocardial protection after OPCAB with either sevoflurane or desflurane or TIVA using propofol as assessed by measuring serial cTnT values.

  3. Murine calcium-activated chloride channel family member 3 induces asthmatic airway inflammation independently of allergen exposure

    Institute of Scientific and Technical Information of China (English)

    MEI Li; HE Li; WU Si-si; ZHANG Bo; XU Yong-jian; ZHANG Zhen-xiang; ZHAO Jian-ping

    2013-01-01

    Background Expression of murine calcium-activated chloride channel family member 3 (mCLCA3) has been reported to be increased in the airway epithelium of asthmatic mice challenged with ovalbumin (OVA).However,its role in asthmatic airway inflammation under no OVA exposure has not yet been clarified.Methods mCLCA3 plasmids were transfected into the airways of normal BALB/c mice.mCLCA3 expression and airway inflammation in mouse lung tissue were evaluated.Cell differentials and cytokines in bronchoalveolar lavage fluid (BALF) were analyzed.The expression of mCLCA3 protein and mucus protein mucin-5 subtype AC (MUC5AC) were analyzed by Western blotting.The mRNA levels of mCLCA3,MUC5AC and interleukin-13 (IL-13) were determined quantitatively.Results mCLCA3 expression was not detected in the control group while strong immunoreactivity was detected in the OVA and mCLCA3 plasmid groups,and was strictly localized to the airway epithelium.The numbers of inflammatory cells in lung tissue and BALF were increased in both mCLCA3 plasmid and OVA groups.The protein and mRNA levels of mCLCA3 and MUC5AC in the lung tissue were significantly increased in the mCLCA3 plasmid and OVA groups compared to the control group.The level of IL-13,but not IL-4,IL-5,IFN-γ,CCL2,CCL5 or CCL11,was significantly increased compared with control group in BALF in the mCLCA3 plasmid and OVA groups.The level of IL-13 in the BALF in the mCLCA3 plasmid group was much higher than that in the OVA group (P <0.05).The level of mCLCA3 mRNA in lung tissue was positively correlated with the levels of MUC5AC mRNA in lung tissue,IL-13 mRNA in lung tissue,the number of eosinophils in BALF,and the content of IL-13 protein in BALF.The level of IL-13 mRNA in lung tissue was positively correlated with the number of eosinophils in BALF and the level of MUC5AC mRNA in lung tissue.Conclusion These findings suggest that increased expression of a single-gene,mCLCA3,could simulate an asthma attack,and its mechanism may

  4. Effects of lung inflation on airway heterogeneity during histaminergic bronchoconstriction.

    Science.gov (United States)

    Kaczka, David W; Mitzner, Wayne; Brown, Robert H

    2013-09-01

    Lung inflation has been shown to dilate airways by altering the mechanical equilibrium between opposing airway and parenchymal forces. However, it is not known how heterogeneously such dilation occurs throughout the airway tree. In six anesthetized dogs, we measured the diameters of five to six central airway segments using high-resolution computed tomography, along with respiratory input impedance (Zrs) during generalized aerosol histamine challenge, and local histamine challenge in which the agonist was instilled directly onto the epithelia of the imaged central airways. Airway diameters and Zrs were measured at 12 and 25 cmH2O. The Zrs spectra were fitted with a model that incorporated continuous distributions of airway resistances. Airway heterogeneity was quantified using the coefficient of variation for predefined airway distribution functions. Significant reductions in average central airway diameter were observed at 12 cmH2O for both aerosolized and local challenges, along with significant increases upon inflation to 25 cmH2O. No significant differences were observed for the coefficient of variation of airway diameters under any condition. Significant increases in effective airway resistance as measured by Zrs were observed only for the aerosolized challenge at 12 cmH2O, which was completely reversed upon inflation. We conclude that the lung periphery may be the most dominant contributor to increases in airway resistance and tissue elastance during bronchoconstriction induced by aerosolized histamine. However, isolated constriction of only a few central airway segments may also affect tissue stiffness via interdependence with their surrounding parenchyma.

  5. Ozone-induced increases in substance P and 8-epi-prostaglandin F2 alpha in the airways of human subjects

    Energy Technology Data Exchange (ETDEWEB)

    Hazbun, M.E.; Hamilton, R.; Holian, A.; Eschenbacher, W.L. (Baylor College of Medicine, Houston, TX (United States))

    1993-11-01

    We are interested in the mechanisms of ozone-induced lung effects after short-term exposure and the relationship with subsequent pulmonary inflammation and disease. Our hypothesis is that ozone, as a powerful oxidant, will diminish the activity of neutral endopeptidase (NEP) in the airways of humans with resulting increased concentrations of neuropeptides such as substance P (SP). We have exposed seven (two women, five men) healthy, nonsmoking individuals (22 to 30 yr of age) to filtered air and ozone (0.25 ppm) for 1 h in an environmental chamber during heavy exercise. Bronchoscopy with airway lavage (AL) and bronchoalveolar lavage (BAL) was performed immediately after ozone exposure. The lavage samples were analyzed by enzyme immunoassay for SP and 8-epi-prostaglandin F2 alpha (8-epi-PGF2 alpha) (a marker for oxidative free radical reaction) and by radioimmunoassay for complement fragments. FEV1 had declined 12.4 +/- 1.9% (mean +/- SEM) as a result of ozone exposure. The AL concentration for SP and 8-epi-PGF2 alpha and BAL concentration of C3a after ozone exposure were significantly higher than after the filtered air exposure (P < 0.05). There was a significant correlation between SP and 8-epi-PGF2 alpha concentrations in the AL fluid (r2 = 0.89 and P < 0.05). There were no changes in C5a in either compartment or any of the mediators in the plasma samples. These results extend previous results from animal studies suggesting that ozone's mechanism of action is through an oxidative reaction resulting in a decreased activity of NEP in the airways with a subsequent increase in the concentration and activity of SP.

  6. Comparison of surgical condition in endoscopic sinus surgery using remifentanil combined with propofol, sevoflurane, or desflurane.

    Science.gov (United States)

    Yoo, Hyung-Seok; Han, Jin Hee; Park, Sung Wook; Kim, Keon Sik

    2010-12-01

    Various maneuvers are commonly used to achieve the ideal operative field necessary for successful endoscopic sinus surgery (ESS). There are a few contradictory reports on this subject and the consensus is that propofol anesthesia results in a better or similar surgical field and less or similar amount of bleeding than volatile anesthesia. The aim of this study was to compare the surgical field in patients in whom intravenous anesthesia is used as opposed to balanced general anesthesia. SIXTY PATIENTS UNDERGOING ESS WERE RANDOMLY ASSIGNED INTO THREE GROUPS, EACH OF WHICH USED A DIFFERENT TYPE OF ANESTHESIA: propofol/remifentanil (PRO/REM) group, sevoflurane/remifentanil (SEV/REM) group, and desflurane/remifentanil (DES/REM) group. We aimed to maintain the intraoperative mean blood pressure (MBP) at 65 mmHg and the heartrate (HR) at about 75 beats per minute. The quality of visibility of the surgical field was graded, using a validated scoring system, 60 minutes after the start of the operation. All groups had a similar MBP and mean HR at 60 minutes after the operation started. There was no significant differences among the three groups for surgical grade score (P = 0.83). In this comparative study of three anesthetic combinations (PRO/REM, SEV/REM, and DES/REM) in patients undergoing ESS with controlled BP and HR, we did not observe any significant differences in the surgical grade scores.

  7. Airway management in trauma

    Directory of Open Access Journals (Sweden)

    Rashid M Khan

    2011-01-01

    Full Text Available Trauma has assumed epidemic proportion. 10% of global road accident deaths occur in India. Hypoxia and airway mismanagement are known to contribute up to 34% of pre-hospital deaths in these patients. A high degree of suspicion for actual or impending airway obstruction should be assumed in all trauma patients. Objective signs of airway compromise include agitation, obtundation, cyanosis, abnormal breath sound and deviated trachea. If time permits, one should carry out a brief airway assessment prior to undertaking definitive airway management in these patients. Simple techniques for establishing and maintaining airway patency include jaw thrust maneuver and/or use of oro- and nas-opharyngeal airways. All attempts must be made to perform definitive airway management whenever airway is compromised that is not amenable to simple strategies. The selection of airway device and route- oral or -nasal, for tracheal intubation should be based on nature of patient injury, experience and skill level.

  8. The laminin beta 1-competing peptide YIGSR induces a hypercontractile, hypoproliferative airway smooth muscle phenotype in an animal model of allergic asthma

    NARCIS (Netherlands)

    Dekkers, Bart G. J.; Bos, I. Sophie T.; Halayko, Andrew J.; Zaagsma, Johan; Meurs, Herman

    2010-01-01

    Background: Fibroproliferative airway remodelling, including increased airway smooth muscle (ASM) mass and contractility, contributes to airway hyperresponsiveness in asthma. In vitro studies have shown that maturation of ASM cells to a (hyper)contractile phenotype is dependent on laminin, which can

  9. Involvement of large-conductance Ca2+-activated K+ channels in chloroquine-induced force alterations in pre-contracted airway smooth muscle.

    Directory of Open Access Journals (Sweden)

    Ming-Yu Wei

    Full Text Available The participation of large-conductance Ca2+ activated K+ channels (BKs in chloroquine (chloro-induced relaxation of precontracted airway smooth muscle (ASM is currently undefined. In this study we found that iberiotoxin (IbTx, a selective inhibitor of BKs and chloro both completely blocked spontaneous transient outward currents (STOCs in single mouse tracheal smooth muscle cells, which suggests that chloro might block BKs. We further found that chloro inhibited Ca2+ sparks and caffeine-induced global Ca2+ increases. Moreover, chloro can directly block single BK currents completely from the intracellular side and partially from the extracellular side. All these data indicate that the chloro-induced inhibition of STOCs is due to the blockade of chloro on both BKs and ryanodine receptors (RyRs. We also found that low concentrations of chloro resulted in additional contractions in tracheal rings that were precontracted by acetylcholine (ACH. Increases in chloro concentration reversed the contractile actions to relaxations. In the presence of IbTx or paxilline (pax, BK blockers, chloro-induced contractions were inhibited, although the high concentrations of chloro-induced relaxations were not affected. Taken together, our results indicate that chloro blocks BKs and RyRs, resulting in abolishment of STOCs and occurrence of contraction, the latter will counteract the relaxations induced by high concentrations of chloro.

  10. Resolution of cell-mediated airways diseases

    Science.gov (United States)

    2010-01-01

    "Inflammation resolution" has of late become a topical research area. Activation of resolution phase mechanisms, involving select post-transcriptional regulons, transcription factors, 'autacoids', and cell phenotypes, is now considered to resolve inflammatory diseases. Critical to this discourse on resolution is the elimination of inflammatory cells through apoptosis and phagocytosis. For major inflammatory diseases such as asthma and COPD we propose an alternative path to apoptosis for cell elimination. We argue that transepithelial migration of airway wall leukocytes, followed by mucociliary clearance, efficiently and non-injuriously eliminates pro-inflammatory cells from diseased airway tissues. First, it seems clear that numerous infiltrated granulocytes and lymphocytes can be speedily transmitted into the airway lumen without harming the epithelial barrier. Then there are a wide range of 'unexpected' findings demonstrating that clinical improvement of asthma and COPD is not only associated with decreasing numbers of airway wall inflammatory cells but also with increasing numbers of these cells in the airway lumen. Finally, effects of inhibition of transepithelial migration support the present hypothesis. Airway inflammatory processes have thus been much aggravated when transepithelial exit of leukocytes has been inhibited. In conclusion, the present hypothesis highlights risks involved in drug-induced inhibition of transepithelial migration of airway wall leukocytes. It helps interpretation of common airway lumen data, and suggests approaches to treat cell-mediated airway inflammation. PMID:20540713

  11. Adenovirus-mediated Foxp3 expression in lung epithelial cells reduces airway inflammation in ovalbumin and cockroach-induced asthma model

    Science.gov (United States)

    Park, Soojin; Chung, Hwan-Suck; Shin, Dasom; Jung, Kyung-Hwa; Lee, Hyunil; Moon, Junghee; Bae, Hyunsu

    2016-01-01

    Foxp3 is a master regulator of CD4+CD25+ regulatory T-cell (Treg) function and is also a suppressor of SKP2 and HER2/ErbB2. There are an increasing number of reports describing the functions of Foxp3 in cell types other than Tregs. In this context, we evaluated the functions of Foxp3 in ovalbumin- and cockroach-induced asthma models. Foxp3-EGFP-expressing adenovirus or EGFP control adenovirus was administered intratracheally (i.t.), followed by challenge with ovalbumin (OVA) or cockroach extract to induce asthma. Th2 cytokine and immune cell profiles of bronchoalveolar lavage fluid (BALF), as well as serum IgE levels, were analyzed. Histological analyses were also conducted to demonstrate the effects of Foxp3 expression on airway remodeling, goblet cell hyperplasia and inflammatory responses in the lung. Adenoviral Foxp3 was expressed only in lung epithelial cells, and not in CD4+ or CD8+ cells. BALF from Foxp3 gene-delivered mice showed significantly reduced numbers of total immune cells, eosinophils, neutrophils, macrophages and lymphocytes in response to cockroach allergen or OVA. In addition, Foxp3 expression in the lung reduced the levels of Th2 cytokines and IgE in BALF and serum, respectively. Moreover, histopathological analysis also showed that Foxp3 expression substantially inhibited eosinophil infiltration into the airways, goblet cell hyperplasia and smooth muscle cell hypertrophy. Furthermore, when Tregs were depleted by diphtheria toxin in Foxp3DTR mice, the anti-asthmatic functions of Foxp3 were not altered in OVA-challenged asthma models. In this study, our results suggest that Foxp3 expression in lung epithelial cells, and not in Tregs, inhibited OVA- and cockroach extract-induced asthma. PMID:27633092

  12. Plasma levels of interleukin-10 and nitric oxide in response to two different desflurane anesthesia flow rates

    Directory of Open Access Journals (Sweden)

    Dilek Kalayci

    2014-07-01

    Full Text Available OBJECTIVE: This study investigated interleukin-10 and nitric oxide plasma levels following surgery to determine whether there is a correlation between these two variables and if different desflurane anesthesia flow rates influence nitric oxide and interleukin-10 concentrations in circulation. MATERIALS AND METHODS: Forty patients between 18 and 70 years and ASA I-II physical status who were scheduled to undergo thyroidectomy were enrolled in the study. INTERVENTIONS: Patients were allocated into two groups to receive two different desflurane anesthesia flow rates: high flow (Group HF and low flow (Group LF. MEASUREMENTS: Blood samples were drawn at the beginning (t 0 and end (t 1 of the operation and after 24 h (t 2. Plasma interleukin-10 and nitric oxide levels were measured using an enzyme-linked-immunosorbent assay and a Griess reagents kit, respectively. Hemodynamic and respiratory parameters were assessed. RESULTS: There was no statistically significant difference between the two groups with regard to interleukin-10 levels at the times of measurement. Interleukin-10 levels were increased equally in both groups at times t 1 and t 2 compared with preoperative concentrations. For both groups, nitric oxide circulating concentrations were significantly reduced at times t 1 and t 2 compared with preoperative concentrations. However, the nitric oxide value was lower for Group HF compared to Group LF at t 2. No correlation was found between the IL-10 and nitric oxide levels. CONCLUSION: Clinical usage of two different flow anesthesia forms with desflurane may increase interleukin-10 levels both in Group HF and Group LF; nitric oxide levels circulating concentrations were significantly reduced at times t 1 and t 2 compared with preoperative concentrations; however, at 24 h postoperatively they were higher in Group LF compared to Group HF. No correlation was detected between interleukin-10 and nitric oxide levels.

  13. Sevoflurane causes less arrhythmias than desflurane after off-pump coronary artery bypass grafting: A pilot study

    Directory of Open Access Journals (Sweden)

    Hemmerling Thomas

    2010-01-01

    Full Text Available Background: Volatile anesthetics provide myocardial protection during cardiac surgery. Sevoflurane and desflurane are both efficient agents that allow immediate extubation after off-pump coronary artery bypass grafting (OPCABG. This study compared the incidence of arrhythmias after OPCABG with the two agents. Materials and Methods: Forty patients undergoing OPCABG with immediate extubation and perioperative high thoracic analgesia were included in this controlled, double-blind study; anesthesia was either provided using 1 MAC of sevoflurane (SEVO-group or desflurane (DES-group. Monitoring of perioperative arrhythmias was provided by continuous monitoring of the EKG up to 72 hours after surgery, and routine EKG monitoring once every day, until time of discharge. Patient data, perioperative arrhythmias, and myocardial protection (troponin I, CK, CK-MB-ratio, and transesophageal echocardiography examinations were compared using t-test, Fisher′s exact test or two-way analysis of variance for repeated measurements; P < 0.05. Results: Patient data and surgery-related data were similar between the two groups; all the patients were successfully extubated immediately after surgery, with similar emergence times. Supraventricular tachycardia occurred only in the DES-group (5 of 20 patients, atrial fibrillation was significantly more frequent in the DES group versus SEVO-group, at five out of 20 versus one out of 20 patients, respectively. Myocardial protection was equally achieved in both groups. Discussion: Ultra-fast track anesthesia using sevoflurane seems more advantageous than desflurane for anesthesia, for OPCABG, as it is associated with significantly less atrial fibrillation or supraventricular arrhythmias after surgery.

  14. [Plasma levels of interleukin-10 and nitric oxide in response to two different desflurane anesthesia flow rates].

    Science.gov (United States)

    Kalayci, Dilek; Dikmen, Bayazit; Kaçmaz, Murat; Taşpınar, Vildan; Ornek, Dilşen; Turan, Ozlem

    2014-01-01

    This study investigated interleukin-10 and nitric oxide plasma levels following surgery to determine whether there is a correlation between these two variables and if different desflurane anesthesia flow rates influence nitric oxide and interleukin-10 concentrations in circulation. Forty patients between 18 and 70 years and ASA I-II physical status who were scheduled to undergo thyroidectomy were enrolled in the study. Patients were allocated into two groups to receive two different desflurane anesthesia flow rates: high flow (Group HF) and low flow (Group LF). Blood samples were drawn at the beginning (t0) and end (t1) of the operation and after 24h (t2). Plasma interleukin-10 and nitric oxide levels were measured using an enzyme-linked-immunosorbent assay and a Griess reagents kit, respectively. Hemodynamic and respiratory parameters were assessed. There was no statistically significant difference between the two groups with regard to interleukin-10 levels at the times of measurement. Interleukin-10 levels were increased equally in both groups at times t1 and t2 compared with preoperative concentrations. For both groups, nitric oxide circulating concentrations were significantly reduced at times t1 and t2 compared with preoperative concentrations. However, the nitric oxide value was lower for Group HF compared to Group LF at t2. No correlation was found between the IL-10 and nitric oxide levels. Clinical usage of two different flow anesthesia forms with desflurane may increase interleukin-10 levels both in Group HF and Group LF; nitric oxide levels circulating concentrations were significantly reduced at times t1 and t2 compared with preoperative concentrations; however, at 24h postoperatively they were higher in Group LF compared to Group HF. No correlation was detected between interleukin-10 and nitric oxide levels. Copyright © 2013 Sociedade Brasileira de Anestesiologia. Publicado por Elsevier Editora Ltda. All rights reserved.

  15. Comparison of an infrared anaesthetic agent analyser (Datex-Ohmeda) with refractometry for measurement of isoflurane, sevoflurane and desflurane concentrations.

    Science.gov (United States)

    Rudolff, Andrea S; Moens, Yves P S; Driessen, Bernd; Ambrisko, Tamas D

    2014-07-01

    To assess agreement between infrared (IR) analysers and a refractometer for measurements of isoflurane, sevoflurane and desflurane concentrations and to demonstrate the effect of customized calibration of IR analysers. In vitro experiment. Six IR anaesthetic monitors (Datex-Ohmeda) and a single portable refractometer (Riken). Both devices were calibrated following the manufacturer's recommendations. Gas samples were collected at common gas outlets of anaesthesia machines. A range of agent concentrations was produced by stepwise changes in dial settings: isoflurane (0-5% in 0.5% increments), sevoflurane (0-8% in 1% increments), or desflurane (0-18% in 2% increments). Oxygen flow was 2 L minute(-1) . The orders of testing IR analysers, agents and dial settings were randomized. Duplicate measurements were performed at each setting. The entire procedure was repeated 24 hours later. Bland-Altman analysis was performed. Measurements on day-1 were used to yield calibration equations (IR measurements as dependent and refractometry measurements as independent variables), which were used to modify the IR measurements on day-2. Bias ± limits of agreement for isoflurane, sevoflurane and desflurane were 0.2 ± 0.3, 0.1 ± 0.4 and 0.7 ± 0.9 volume%, respectively. There were significant linear relationships between differences and means for all agents. The IR analysers became less accurate at higher gas concentrations. After customized calibration, the bias became almost zero and the limits of agreement became narrower. If similar IR analysers are used in research studies, they need to be calibrated against a reference method using the agent in question at multiple calibration points overlapping the range of interest. © 2013 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesia and Analgesia.

  16. Plasma levels of interleukin-10 and nitric oxide in response to two different desflurane anesthesia flow rates.

    Science.gov (United States)

    Kalaycı, Dilek; Dikmen, Bayazit; Kaçmaz, Murat; Taşpınar, Vildan; Ornek, Dilşen; Turan, Ozlem

    2014-01-01

    This study investigated interleukin-10 and nitric oxide plasma levels following surgery to determine whether there is a correlation between these two variables and if different desflurane anesthesia flow rates influence nitric oxide and interleukin-10 concentrations in circulation. Forty patients between 18 and 70 years and ASA I-II physical status who were scheduled to undergo thyroidectomy were enrolled in the study. Patients were allocated into two groups to receive two different desflurane anesthesia flow rates: high flow (Group HF) and low flow (Group LF). Blood samples were drawn at the beginning (t0) and end (t1) of the operation and after 24h (t2). Plasma interleukin-10 and nitric oxide levels were measured using an enzyme-linked-immunosorbent assay and a Griess reagents kit, respectively. Hemodynamic and respiratory parameters were assessed. There was no statistically significant difference between the two groups with regard to interleukin-10 levels at the times of measurement. Interleukin-10 levels were increased equally in both groups at times t1 and t2 compared with preoperative concentrations. For both groups, nitric oxide circulating concentrations were significantly reduced at times t1 and t2 compared with preoperative concentrations. However, the nitric oxide value was lower for Group HF compared to Group LF at t2. No correlation was found between the IL-10 and nitric oxide levels. Clinical usage of two different flow anesthesia forms with desflurane may increase interleukin-10 levels both in Group HF and Group LF; nitric oxide levels circulating concentrations were significantly reduced at times t1 and t2 compared with preoperative concentrations; however, at 24h postoperatively they were higher in Group LF compared to Group HF. No correlation was detected between interleukin-10 and nitric oxide levels. Copyright © 2013 Sociedade Brasileira de Anestesiologia. Published by Elsevier Editora Ltda. All rights reserved.

  17. The role of potassium channels in the nitric oxide-induced relaxation of human airway smooth muscle of passively sensitization by serum from allergic asthmatic patients

    Institute of Scientific and Technical Information of China (English)

    Tao Ye; Yongjian Xu; Zhenxiang Zhang; Xiansheng Liu; Zhao Yang; Baoan Gao

    2006-01-01

    Objective: To investigate the role of large Ca2+-activated, delayed-rectifier and ATP-sensitive potassium channel in regulating the relaxation induced by nitric oxide (NO) in normal and passively sensitized human airway smooth muscle (HASM) with serum from asthmatic patients. Methods: The effects of NO or/and potassium channel blockers on the tensions of normal and passively sensitized HASM were measured by using nitric oxide donor and potassium blockers, with the isometric tension recording technique. Results: Showed that (1)In the control group and passively sensitized group, Kv blocker (4-AP) cause concentration-dependent augmentation in the contraction induced by histamine (1 ×10-4 mol/L), (P < 0.05), but Glib (1 × 10-2 mol/L)and TEA (1×10-3 mol/L) have no significant effects on the contraction induced by histamine (1×10-4 mol/L). The maximum tension induced by histamine in passively sensitized group is higher than that in the control group (P < 0.05). (2) NO-donor Sodium Nitroprusside (SNP) bring about significant relaxation in normal and passively sensitized HASM rings (P < 0.05). Relaxations of passively sensitized airway rings [ (29.4 ± 3.3)% ] were significant less than those of normal HASM rings [ (44.1 ± 10.2)% ], (P <0.05).(3) Glib(1×10-2 mol/L)have no significant effect on the relaxations induced by SNP(1×10-4 mol/L). 4-AP(1×10-2 mol/L) inhibited relaxation induced by SNP (1×10-4 mol/L), (P < 0.01). TEA (1×10-3 mol/L) inhibited relaxation induced by SNP (1×10-4mol/L) (P < 0.05), and the inhibiting effect in passively sensitized HASM rings were significant less than in normal HASM, (P <0.05). Conclusion: It was concluded that SNP(NO-donor) relaxed the contraction of HASM partly via BKca channel opening. In passively sensitized HASM in vitro, the relaxation of SNP decreased compared with control group, which might be associated with the down-regulating activity of BKca in passively sensitized HASM.

  18. Eosinophilic airway inflammation in asthmatic patients is associated with an altered airway microbiome

    DEFF Research Database (Denmark)

    Sverrild, Asger; Kiilerich, Pia; Brejnrod, Asker Daniel

    2017-01-01

    healthy control subjects. Bacterial DNA was extracted from and subjected to Illumina MiSeq sequencing of the 16S rDNA V4 region. Eosinophils and neutrophils in the submucosa were quantified by means of immunohistochemical identification and computerized image analysis. Induced sputum was obtained......, and airway hyperresponsiveness to mannitol and fraction of exhaled nitric oxide values were measured. Relationships between airway microbial diversity and composition and inflammatory profiles were analyzed. RESULTS: In asthmatic patients airway microbial composition was associated with airway eosinophilia...

  19. Airway distensibility in Chronic Obstructive Airway Disease

    DEFF Research Database (Denmark)

    Winkler Wille, Mathilde Marie; Pedersen, Jesper Holst; Dirksen, Asger

    2013-01-01

    Rationale – Chronic Obstructive Pulmonary Disease (COPD) is a combination of chronic bronchitis and emphysema, which both may lead to airway obstruction. Under normal circumstances, airway dimensions vary as a function of inspiration level. We aim to study the influence of COPD and emphysema...... and emphysema, respectively. Conclusions – Airway distensibility decreases significantly with increasing severity of both GOLD status and emphysema, indicating that in COPD the dynamic change in airway calibre during respiration is compromised. Chronic bronchitis and emphysema appear to be interacting...

  20. Verproside inhibits TNF-α-induced MUC5AC expression through suppression of the TNF-α/NF-κB pathway in human airway epithelial cells.

    Science.gov (United States)

    Lee, Su Ui; Sung, Min Hee; Ryu, Hyung Won; Lee, Jinhyuk; Kim, Hui-Seong; In, Hyun Ju; Ahn, Kyung-Seop; Lee, Hyun-Jun; Lee, Hyeong-Kyu; Shin, Dae-Hee; Lee, Yongnam; Hong, Sung-Tae; Oh, Sei-Ryang

    2016-01-01

    Airway mucus secretion is an essential innate immune response for host protection. However, overproduction and hypersecretion of mucus, mainly composed of MUC5AC, are significant risk factors in asthma and chronic obstructive pulmonary disease (COPD) patients. Previously, we reported that verproside, a catalpol derivative iridoid glycoside isolated from Pseudolysimachion rotundum var. subintegrum, is a potent anti-asthmatic candidate drug in vivo. However, the molecular mechanisms underlying the pharmacological actions of verproside remain unknown. Here, we found that verproside significantly reduces the expression levels of tumor necrosis factor alpha (TNF-α)-induced MUC5AC mRNA and protein by inhibiting both nuclear factor kappa B (NF-κB) transcriptional activity and the phosphorylation of its upstream effectors such as IκB kinase (IKK)β, IκBα, and TGF-β-activated kinase 1 (TAK1) in NCI-H292 cells. Moreover, verproside attenuated TNF-α-induced MUC5AC transcription more effectively when combined with an IKK (BAY11-7082) or a TAK1 (5z-7-oxozeaenol) inhibitor than when administered alone. Importantly, we demonstrated that verproside negatively modulates the formation of the TNF-α-receptor (TNFR) 1 signaling complex [TNF-RSC; TNFR1-recruited TNFR1-associated death domain protein (TRADD), TNFR-associated factor 2 (TRAF2), receptor-interacting protein kinase 1 (RIP1), and TAK1], the most upstream signaling factor of NF-κB signaling. In silico molecular docking studies show that verproside binds between TRADD and TRAF2 subunits. Altogether, these results suggest that verproside could be a good therapeutic candidate for treatment of inflammatory airway diseases such as asthma and COPD by blocking the TNF-α/NF-κB signaling pathway.

  1. The effect of synthetic salidroside on cytokines and airway inflammation of asthma induced by diisocyanate (TDI) in mice by regulating GATA3/T-bet.

    Science.gov (United States)

    Wang, Jing; Xiao, Lu; Zhu, Lingpeng; Hu, Mei; Wang, Qiujuan; Yan, Tianhua

    2015-04-01

    This study was conducted to explore the anti-asthma effects of synthetic salidroside on cytokines and airway inflammation of asthma induced by diisocyanate (TDI) in mice. The experiment was carried out 60 female BALB/C mice which were randomly assigned to six experimental groups: control, vehicle, model, dexamethasone (2 mg/kg), and salidroside (24 and 48 mg/kg). After the experiment, histological studies were evaluated by the hematoxylin and eosin staining, the bronchoalveolar lavage fluid (BALF) and blood were collected from the animals, and the composition of the induced inflammatory cells, and the concentrations of certain cytokines (IL-4, INF-γ) were evaluated. GATA3 and T-bet mRNAs were evaluated by QPCR. Our study demonstrated that salidroside inhibited TDI-induced increases in eosinophil count; IL-4 and INF-γ were recovered. Histological studies demonstrated that salidroside substantially inhibited TDI-induced eosinophilia in lung tissue. Salidroside can improve T-bet mRNA and reduce GATA3 mRNA in lung. These findings suggest that salidroside may effectively ameliorate the progression of asthma and could be used as a therapy for patients with allergic asthma by regulating GATA3/T-bet balance.

  2. Inhibitory effect of Chinese green tea on cigarette smoke-induced up-regulation of airway neutrophil elastase and matrix metalloproteinase-12 via antioxidant activity.

    Science.gov (United States)

    Chan, Ka Ho; Chan, Stanley Chi Hang; Yeung, Sze Chun; Man, Ricky Ying Keung; Ip, Mary Sau Man; Mak, Judith Choi Wo

    2012-09-01

    Our recent study has indicated that Chinese green tea (Lung Chen), in which epigallocatechin-3-gallate (EGCG) accounts for 60% of catechins, protected cigarette smoke-induced lung injury. We now hypothesized that Lung Chen tea may also have potential effect on lung oxidative stress and proteases/anti-proteases in a smoking rat model. Sprague-Dawley rats were exposed to either sham air (SA) or 4% cigarette smoke (CS) plus 2% Lung Chen tea or water by oral gavage. Serine proteases, matrix metalloproteinases (MMPs) and their respective endogenous inhibitors were determined in bronchoalveolar lavage (BAL) and lung tissues by gelatin/casein zymography and biochemical assays. Green tea consumption significantly decreased CS-induced elevation of lung lipid peroxidation marker, malondialdehyde (MDA), and CS-induced up-regulation of neutrophil elastase (NE) concentration and activity along with that of α(1)-antitrypsin (α(1)-AT) and secretory leukoproteinase inhibitor (SLPI) in BAL and lung. In parallel, significant elevation of MMP-12 activity was found in BAL and lung of the CS-exposed group, which returned to the levels of SA-exposed group after green tea consumption but not CS-induced reduction of tissue inhibitor of metalloproteinase (TIMP)-1 activity, which was not reversed by green tea consumption. Taken together, our data supported the presence of local oxidative stress and protease/anti-protease imbalance in the airways after CS exposure, which might be alleviated by green tea consumption through its biological antioxidant activity.

  3. DNA vaccine encoding Der p 2 allergen generates immunologic protection in recombinant Der p 2 allergen-induced allergic airway inflammation mice model

    Institute of Scientific and Technical Information of China (English)

    LI Guo-ping; LIU Zhi-gang; QIU Jing; RAN Pi-xin; ZHONG Nan-shan

    2005-01-01

    Background DNA immunization is a promising novel type of immunotherapy against allergy. An estimated 79.2% patients with asthma, wheezing and/or rhinitis suffer from Dermatophagoides pteronyssinus group 2 (Der p 2) allegen. The aim of the present study was to determine whether DNA vaccine encoding Der p 2 could generate immunologic protection in recombinant Der p 2 (rDer p 2) allergen-induced allergic airway inflammation mice model and to understand the role of DNA vaccination in specific-allergen immunotherapy for asthma. Methods After DNA vaccination, BALB/c mice were sensitized by intraperitoneal injection (i.p) and challenged by intranasal instillation of rDer p 2. The lung tissues were assessed using hematoxylin and eosin. Mucus-producing goblet cells were identifed using periodic acid-Schiff(PAS)/alcian blue. The total cell number and composition of bronchoalveolar lavage samples were determined. The levels of the cytokines IL-4 and IFN-γ, as well as IgE and IgG2a in the serum were determined by enzyme-linked immunosorbent assay. Allergen-specific IL-4 and IFN-γ production by spleen cells were also measured by enzyme-linked immunosorbent assay. Expression of signal transducer and activator of transcription 6 (STAT6) in splenocytes were determined by Western blot. Results DNA vaccine encoding Der p 2 allergen inhibited extensive infiltration of inflammatory cells and production of mucin induced by allergen. The influx of eosinophils into the lung interstitium was significantly reduced after administration of DNA vaccine. Significant reductions of IL-4 and increase in levels of IFN-γ in bronchoalveolar lavage fluid were observed. The allergen-specific IgE was markedly decreased in mice receiving DNA vaccination. Allergen could induce higher IFN-γ, weaker IL-4 in cultured spleen cells from mice receiving DNA vaccine. DNA vaccination inhibited STAT6 expression of spleen cells induced by allergen. Conclusion These results indicated that DNA vaccine encoding

  4. The effects of desflurane and sevoflurane on the intraocular pressure associated with endotracheal intubation in pediatric ophthalmic surgery.

    Science.gov (United States)

    Park, Jong Taek; Lim, Hyun Kyo; Jang, Kyu-Yong; Um, Dea Ja

    2013-02-01

    For ophthalmic surgery anesthesia, it is vital that intraocular pressure (IOP) is controlled. Most anesthetic drugs affect IOP dose-dependently, and inhalational anesthetics dose-dependently decrease IOP. In this study, we compared the effects of desflurane and sevoflurane on IOP and hemodynamics in pediatric ophthalmic surgery. Thirty eight pediatric patients from the age of 6 to 15 years, who were scheduled for strabismus surgery and entropion surgery, were randomized to be administered desflurane (group D, n = 19) or sevoflurane (group S, n = 19). IOPs and hemodynamic parameters were measured before induction of anesthesia (B), after induction but immediately before intubation (AI), 1 min after intubation (T1), 3 min after intubation (T3), and 5 min after intubation (T5). The mean arterial pressure (MAP) at T1 and heart rates (HRs) at T1 and T3 were significantly higher in group D than those in group S. There was no significant difference between the groups in IOP, cardiac index (CI) and stroke index (SI). There was a significant difference within the group in IOP, SI, MAP and HR. There was no significant difference within the group in CI. There was no significant difference between the groups in IOP and hemodynamic parameters. The two anesthetic agents maintained IOP and hemodynamic parameters in the normal range during anesthetic induction.

  5. TCDD-Induced Activation of Aryl Hydrocarbon Receptor Inhibits Th17 Polarization and Regulates Non-Eosinophilic Airway Inflammation in Asthma

    OpenAIRE

    Xiao-ming Li; Juan Peng; Wen Gu; Xue-jun Guo

    2016-01-01

    The aryl hydrocarbon receptor (AhR), a transcription factor of the bHLH/PAS family, has recently been demonstrated to regulate T cell differentiation. Whether AhR activation participates in allergic airway inflammation remains unknown. In the current study, using a non-eosinophilic asthma model, we demonstrate that 2, 3, 7, 8-tetrachlorodibenzo-P-dioxin (TCDD), a potent AhR ligand, reduced the airway infiltration of neutrophils, airway hyperresponsiveness and Th17 cytokine expression. Further...

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

    Science.gov (United States)

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

    2015-04-20

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

  7. Capsular Polysaccharide is a Main Component of Mycoplasma ovipneumoniae in the Pathogen-Induced Toll-Like Receptor-Mediated Inflammatory Responses in Sheep Airway Epithelial Cells

    Directory of Open Access Journals (Sweden)

    Zhongjia Jiang

    2017-01-01

    Full Text Available Mycoplasma ovipneumoniae (M. ovipneumoniae is characterized as an etiological agent of primary atypical pneumonia that specifically infects sheep and goat. In an attempt to better understand the pathogen-host interaction between the invading M. ovipneumoniae and airway epithelial cells, we investigated the host inflammatory responses against capsular polysaccharide (designated as CPS of M. ovipneumoniae using sheep bronchial epithelial cells cultured in an air-liquid interface (ALI model. Results showed that CPS derived from M. ovipneumoniae could activate toll-like receptor- (TLR- mediated inflammatory responses, along with an elevated expression of nuclear factor kappa B (NF-κB, activator protein-1 (AP-1, and interferon regulatory factor 3 (IRF3 as well as various inflammatory-associated mediators, representatively including proinflammatory cytokines, such as IL1β, TNFα, and IL8, and anti-inflammatory cytokines such as IL10 and TGFβ of TLR signaling cascade. Mechanistically, the CPS-induced inflammation was TLR initiated and was mediated by activations of both MyD88-dependent and MyD88-independent signaling pathways. Of importance, a blockage of CPS with specific antibody led a significant reduction of M. ovipneumoniae-induced inflammatory responses in sheep bronchial epithelial cells. These results suggested that CPS is a key virulent component of M. ovipneumoniae, which may play a crucial role in the inflammatory response induced by M. ovipneumoniae infections.

  8. Hesperetin-7,3'-O-dimethylether selectively inhibits phosphodiesterase 4 and effectively suppresses ovalbumin-induced airway hyperresponsiveness with a high therapeutic ratio

    Directory of Open Access Journals (Sweden)

    Yang You-Lan

    2011-11-01

    Full Text Available Abstract Background Hesperetin was reported to selectively inhibit phosphodiesterase 4 (PDE4. While hesperetin-7,3'-O-dimethylether (HDME is a synthetic liposoluble hesperetin. Therefore, we were interested in investigating its selectivity on PDE4 and binding ability on high-affinity rolipram-binding sites (HARBs in vitro, and its effects on ovalbumin-induced airway hyperresponsiveness in vivo, and clarifying its potential for treating asthma and chronic obstructive pulmonary disease (COPD. Methods PDE1~5 activities were measured using a two-step procedure. The binding of HDME on high-affinity rolipram-binding sites was determined by replacing 2 nM [3H]-rolipram. AHR was assessed using the FlexiVent system and barometric plethysmography. Inflammatory cells were counted using a hemocytometer. Cytokines were determined using mouse T helper (Th1/Th2 cytokine CBA kits, and total immunoglobulin (IgE or IgG2a levels were done using ELISA method. Xylazine (10 mg/kg/ketamine (70 mg/kg-induced anesthesia was performed. Results HDME revealed selective phosphodiesterase 4 (PDE4 inhibition with a therapeutic (PDE4H/PDE4L ratio of 35.5 in vitro. In vivo, HDME (3~30 μmol/kg, orally (p.o. dose-dependently and significantly attenuated the airway resistance (RL and increased lung dynamic compliance (Cdyn, and decreased enhanced pause (Penh values induced by methacholine in sensitized and challenged mice. It also significantly suppressed the increases in the numbers of total inflammatory cells, macrophages, lymphocytes, neutrophils, and eosinophils, and levels of cytokines, including interleukin (IL-2, IL-4, IL-5, interferon-γ, and tumor necrosis factor-α in bronchoalveolar lavage fluid (BALF of these mice. In addition, HDME (3~30 μmol/kg, p.o. dose-dependently and significantly suppressed total and ovalbumin-specific immunoglobulin (IgE levels in the BALF and serum, and enhanced IgG2a level in the serum of these mice. Conclusions HDME exerted anti

  9. Suppression of ovalbumin-induced Th2-driven airway inflammation by β-sitosterol in a guinea pig model of asthma.

    Science.gov (United States)

    Mahajan, Shailaja G; Mehta, Anita A

    2011-01-10

    In the present study, the efficacy of β-sitosterol isolated from an n-butanol extract of the seeds of the plant Moringa oleifera (Moringaceae) was examined against ovalbumin-induced airway inflammation in guinea pigs. All animals (except group I) were sensitized subcutaneously and challenged with aerosolized 0.5% ovalbumin. The test drugs, β-sitosterol (2.5mg/kg) or dexamethasone (2.5mg/kg), were administered to the animals (p.o.) prior to challenge with ovalbumin. During the experimental period (on days 18, 21, 24 and 29), a bronchoconstriction test (0.25% acetylcholine for 30s) was performed and lung function parameters (tidal volume and respiration rate) were measured for each animal. On day 30, blood and bronchoalveolar lavaged fluid were collected to assess cellular content, and serum was collected for cytokine assays. Lung tissue was utilized for a histamine assay and for histopathology. β-sitosterol significantly increased the tidal volume (V(t)) and decreased the respiration rate (f) of sensitized and challenged guinea pigs to the level of non-sensitized control guinea pigs and lowered both the total and differential cell counts, particularly eosinophils and neutrophils, in blood and bronchoalveolar lavaged fluid. Furthermore, β-sitosterol treatment suppressed the increase in cytokine levels (TNFα, IL-4 and IL-5), with the exception of IL-6, in serum and in bronchoalveolar lavaged fluid detected in model control animals. Moreover, treatment with β-sitosterol protected against airway inflammation in lung tissue histopathology. β-sitosterol possesses anti-asthmatic actions that might be mediated by inhibiting the cellular responses and subsequent release/synthesis of Th2 cytokines. This compound may have therapeutic potential in allergic asthma.

  10. The MIF Antagonist ISO-1 Attenuates Corticosteroid-Insensitive Inflammation and Airways Hyperresponsiveness in an Ozone-Induced Model of COPD.

    Directory of Open Access Journals (Sweden)

    Kirsty E Russell

    Full Text Available Macrophage migration inhibitory factor (MIF is an inflammatory cytokine associated with acute and chronic inflammatory disorders and corticosteroid insensitivity. Its expression in the airways of patients with chronic obstructive pulmonary disease (COPD, a relatively steroid insensitive inflammatory disease is unclear, however.Sputum, bronchoalveolar lavage (BAL macrophages and serum were obtained from non-smokers, smokers and COPD patients. To mimic oxidative stress-induced COPD, mice were exposed to ozone for six-weeks and treated with ISO-1, a MIF inhibitor, and/or dexamethasone before each exposure. BAL fluid and lung tissue were collected after the final exposure. Airway hyperresponsiveness (AHR and lung function were measured using whole body plethysmography. HIF-1α binding to the Mif promoter was determined by Chromatin Immunoprecipitation assays.MIF levels in sputum and BAL macrophages from COPD patients were higher than those from non-smokers, with healthy smokers having intermediate levels. MIF expression correlated with that of HIF-1α in all patients groups and in ozone-exposed mice. BAL cell counts, cytokine mRNA and protein expression in lungs and BAL, including MIF, were elevated in ozone-exposed mice and had increased AHR. Dexamethasone had no effect on these parameters in the mouse but ISO-1 attenuated cell recruitment, cytokine release and AHR.MIF and HIF-1α levels are elevated in COPD BAL macrophages and inhibition of MIF function blocks corticosteroid-insensitive lung inflammation and AHR. Inhibition of MIF may provide a novel anti-inflammatory approach in COPD.

  11. Induction of IL-17A precedes development of airway hyperresponsiveness during diet induced obesity and correlates with complement factor D

    Directory of Open Access Journals (Sweden)

    Joel A. Mathews, Phd

    2014-09-01

    Full Text Available Obesity is a risk factor for the development of asthma. Obese mice exhibit innate airway hyperresponsiveness (AHR, a characteristic feature of asthma, and IL-17A is required for development of AHR in obese mice. The purpose of this study was to examine the temporal association between the onset of AHR and changes in IL-17A during the development of obesity by high fat feeding in mice. At weaning, C57BL/6J mice were placed either on mouse chow or on a high fat diet (HFD and examined 9, 12, 15, 18, or 24 weeks later. Airway responsiveness to aerosolized methacholine (assessed via the forced oscillation technique was greater in mice fed HFD versus chow for 24 weeks, but not at earlier time points. Bronchoalveolar lavage and serum IL-17A were not affected by either the type or duration of diet, but increased pulmonary IL17a mRNA abundance was observed in HFD versus chow fed mice after both 18 and 24 weeks. Flow cytometry also confirmed an increase in IL-17A+ gd T cells and IL-17A+ CD4+ T (Th17 cells in lungs of HFD versus chow fed mice. Pulmonary expression of Cfd (complement factor D, adipsin, a gene whose expression can be reduced by IL-17A, decreased after both 18 and 24 weeks in HFD versus chow fed mice. Furthermore, pulmonary Cfd mRNA abundance correlated with elevations in pulmonary Il17a mRNA expression and with AHR. Serum levels of TNFa, MIP-1a and MIP-1b, classical markers of systemic inflammation of obesity, were significantly greater in HFD than chow fed mice after 24 weeks, but not earlier. In conclusion, our data indicate that pulmonary rather than systemic IL-17A is important for obesity-related AHR and suggest that changes in pulmonary Cfd expression contribute to these effects of IL-17A. Further, the observation that increases in Il17a preceded the development of AHR by several weeks suggests that IL-17A interacts with other factors to promote AHR. The observation that the onset of the systemic inflammation of obesity coincided

  12. Dual effects of vitamin D-induced alteration of TH1/TH2 cytokine expression: enhancing IgE production and decreasing airway eosinophilia in murine allergic airway disease

    DEFF Research Database (Denmark)

    Matheu, Victor; Bäck, Ove; Mondoc, Emma

    2003-01-01

    BACKGROUND: Vitamin D, a common food additive, has been shown to prevent the induction of experimental autoimmune diseases in mice. A possible immune deviation from T(H)1 to T(H)2 responses has been postulated. Although there is no doubt about the beneficial effects of vitamin D, its role in alle...... hold promising beneficial effects in airway eosinophilia....

  13. Effect of unilateral vagus blockade on allergen-induced airway obstruction: results of short- and long-term experiments.

    Science.gov (United States)

    Zimmermann, I; Ulmer, W T

    1977-01-01

    Unilateral application of ascaris extract on segment bronchus as the influence of contralateral vagus blockade on reflex bronchoconstriction was studied on four boxer dogs in a first group (A) of experiments: ascaris extract was applied in liquid form directly through a catheter into the right segment bronchus. This application was repeated after contralateral vagus blockade and once more after its lavage. All the animals showed an increase of airway resistance under local application of ascaris extract which could not be avoided by contralateral central vagus blockade. In the second group (B) isolation of unilateral vagus for reproducible performance of blockade as a long-term model was investigated in three boxer dogs for 7 weeks and the influence of this method of unilateral vagus blockade on exposure to allergen aerosol was studied. The unilateral blockade of the nerve vagus was again always successful in decreasing the reflex bronchoconstriction following allergen inhalation. The effect of unilateral section of nervus vagus 3 weeks after this vagotomy was tested on two boxer dogs. Reflex bronchoconstriction following ascaris extract inhalation can be avoided by unilateral section of the nervus vagus the first time after section. Three weeks after this unilateral vagotomy, the reflex bronchoconstriction becomes managed by the remaining vagus trunk to the same degree as observed by bilateral intact vagi.

  14. Role of growth hormone-releasing hormone in sleep and growth impairments induced by upper airway obstruction in rats.

    Science.gov (United States)

    Tarasiuk, A; Berdugo-Boura, N; Troib, A; Segev, Y

    2011-10-01

    Upper airway obstruction (UAO) can lead to abnormal growth hormone (GH) homeostasis and growth retardation but the mechanisms are unclear. We explored the effect of UAO on hypothalamic GH-releasing hormone (GHRH), which has a role in both sleep and GH regulation. The tracheae of 22-day-old rats were narrowed; UAO and sham-operated animals were sacrificed 16 days post-surgery. To stimulate slow-wave sleep (SWS) and GH secretion, rats were treated with ritanserin (5-HT(2) receptor antagonist). Sleep was measured with a telemetric system. Hypothalamic GHRH, hypothalamic GHRH receptor (GHRHR) and GH receptor, and orexin were analysed using ELISA, real-time PCR and Western blot. UAO decreased hypothalamic GHRH, GHRHR and GH receptor levels, while orexin mRNA increased (psleep and slow-wave activity was reduced (pgrowth impairment (pgrowth retardation in UAO is associated with a reduction in hypothalamic GHRH content. Our findings show that abnormalities in the GHRH/GH axis underlie both growth retardation and SWS-disorder UAO.

  15. Atmospheric chemistry of isoflurane, desflurane, and sevoflurane: kinetics and mechanisms of reactions with chlorine atoms and OH radicals and global warming potentials.

    Science.gov (United States)

    Sulbaek Andersen, Mads P; Nielsen, Ole J; Karpichev, Boris; Wallington, Timothy J; Sander, Stanley P

    2012-06-21

    The smog chamber/Fourier-transform infrared spectroscopy (FTIR) technique was used to measure the rate coefficients k(Cl + CF(3)CHClOCHF(2), isoflurane) = (4.5 ± 0.8) × 10(-15), k(Cl + CF(3)CHFOCHF(2), desflurane) = (1.0 ± 0.3) × 10(-15), k(Cl + (CF(3))(2)CHOCH(2)F, sevoflurane) = (1.1 ± 0.1) × 10(-13), and k(OH + (CF(3))(2)CHOCH(2)F) = (3.5 ± 0.7) × 10(-14) cm(3) molecule(-1) in 700 Torr of N(2)/air diluent at 295 ± 2 K. An upper limit of 6 × 10(-17) cm(3) molecule(-1) was established for k(Cl + (CF(3))(2)CHOC(O)F). The laser photolysis/laser-induced fluorescence (LP/LIF) technique was employed to determine hydroxyl radical rate coefficients as a function of temperature (241-298 K): k(OH + CF(3)CHFOCHF(2)) = (7.05 ± 1.80) × 10(-13) exp[-(1551 ± 72)/T] cm(3) molecule(-1); k(296 ± 1 K) = (3.73 ± 0.08) × 10(-15) cm(3) molecule(-1), and k(OH + (CF(3))(2)CHOCH(2)F) = (9.98 ± 3.24) × 10(-13) exp[-(969 ± 82)/T] cm(3) molecule(-1); k(298 ± 1 K) = (3.94 ± 0.30) × 10(-14) cm(3) molecule(-1). The rate coefficient of k(OH + CF(3)CHClOCHF(2), 296 ± 1 K) = (1.45 ± 0.16) × 10(-14) cm(3) molecule(-1) was also determined. Chlorine atoms react with CF(3)CHFOCHF(2) via H-abstraction to give CF(3)CFOCHF(2) and CF(3)CHFOCF(2) radicals in yields of approximately 83% and 17%. The major atmospheric fate of the CF(3)C(O)FOCHF(2) alkoxy radical is decomposition via elimination of CF(3) to give FC(O)OCHF(2) and is unaffected by the method used to generate the CF(3)C(O)FOCHF(2) radicals. CF(3)CHFOCF(2) radicals add O(2) and are converted by subsequent reactions into CF(3)CHFOCF(2)O alkoxy radicals, which decompose to give COF(2) and CF(3)CHFO radicals. In 700 Torr of air 82% of CF(3)CHFO radicals undergo C-C scission to yield HC(O)F and CF(3) radicals with the remaining 18% reacting with O(2) to give CF(3)C(O)F. Atmospheric oxidation of (CF(3))(2)CHOCH(2)F gives (CF(3))(2)CHOC(O)F in a molar yield of 93 ± 6% with CF(3)C(O)CF(3) and HCOF as minor products. The IR

  16. Type 2 innate lymphoid cell suppression by regulatory T cells attenuates airway hyperreactivity and requires inducible T-cell costimulator-inducible T-cell costimulator ligand interaction.

    Science.gov (United States)

    Rigas, Diamanda; Lewis, Gavin; Aron, Jennifer L; Wang, Bowen; Banie, Homayon; Sankaranarayanan, Ishwarya; Galle-Treger, Lauriane; Maazi, Hadi; Lo, Richard; Freeman, Gordon J; Sharpe, Arlene H; Soroosh, Pejman; Akbari, Omid

    2017-05-01

    Atopic diseases, including asthma, exacerbate type 2 immune responses and involve a number of immune cell types, including regulatory T (Treg) cells and the emerging type 2 innate lymphoid cells (ILC2s). Although ILC2s are potent producers of type 2 cytokines, the regulation of ILC2 activation and function is not well understood. In the present study, for the first time, we evaluate how Treg cells interact with pulmonary ILC2s and control their function. ILC2s and Treg cells were evaluated by using in vitro suppression assays, cell-contact assays, and gene expression panels. Also, human ILC2s and Treg cells were adoptively transferred into NOD SCID γC-deficient mice, which were given isotype or anti-inducible T-cell costimulator ligand (ICOSL) antibodies and then challenged with IL-33 and assessed for airway hyperreactivity. We show that induced Treg cells, but not natural Treg cells, effectively suppress the production of the ILC2-driven proinflammatory cytokines IL-5 and IL-13 both in vitro and in vivo. Mechanistically, our data reveal the necessity of inducible T-cell costimulator (ICOS)-ICOS ligand cell contact for Treg cell-mediated ILC2 suppression alongside the suppressive cytokines TGF-β and IL-10. Using a translational approach, we then demonstrate that human induced Treg cells suppress syngeneic human ILC2s through ICOSL to control airway inflammation in a humanized ILC2 mouse model. These findings suggest that peripheral expansion of induced Treg cells can serve as a promising therapeutic target against ILC2-dependent asthma. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  17. Ferulic Acid Induces Th1 Responses by Modulating the Function of Dendritic Cells and Ameliorates Th2-Mediated Allergic Airway Inflammation in Mice

    Directory of Open Access Journals (Sweden)

    Chen-Chen Lee

    2015-01-01

    Full Text Available This study investigated the immunomodulatory effects of ferulic acid (FA on antigen-presenting dendritic cells (DCs in vitro and its antiallergic effects against ovalbumin- (OVA- induced Th2-mediated allergic asthma in mice. The activation of FA-treated bone marrow-derived DCs by lipopolysaccharide (LPS stimulation induced a high level of interleukin- (IL- 12 but reduced the expression levels of the proinflammatory cytokines IL-1β, IL-6, and tumor necrosis factor- (TNF- α. Compared to control-treated DCs, FA significantly enhanced the expressions of Notch ligand Delta-like 4 (Dll4, MHC class II, and CD40 molecules by these DCs. Furthermore, these FA-treated DCs enhanced T-cell proliferation and Th1 cell polarization. In animal experiments, oral administration of FA reduced the levels of OVA-specific immunoglobulin E (IgE and IgG1 and enhanced IgG2a antibody production in serum. It also ameliorated airway hyperresponsiveness and attenuated eosinophilic pulmonary infiltration in dose-dependent manners. In addition, FA treatment inhibited the production of eotaxin, Th2 cytokines (IL-4, IL-5, and IL-13, and proinflammatory cytokines but promoted the Th1 cytokine interferon- (IFN- γ production in bronchoalveolar lavage fluid (BALF and the culture supernatant of spleen cells. These findings suggest that FA exhibits an antiallergic effect via restoring Th1/Th2 imbalance by modulating DCs function in an asthmatic mouse model.

  18. Anti-inflammatory effects of Tat-Annexin protein on ovalbumin-induced airway inflammation in a mouse model of asthma

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Sun Hwa; Kim, Dae Won; Kim, Hye Ri; Woo, Su Jung; Kim, So Mi; Jo, Hyo Sang [Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chunchon 200-702 (Korea, Republic of); Jeon, Seong Gyu [Department of Life Science, Pohang University of Science and Technology, Pohang 790-784 (Korea, Republic of); Cho, Sung-Woo [Department of Biochemistry and Molecular Biology, University of Ulsan, College of Medicine, Seoul 138-736 (Korea, Republic of); Park, Jong Hoon [Department of Biological Science, Sookmyung Women' s University, Seoul 140-742 (Korea, Republic of); Won, Moo Ho [Department of Neurobiology, School of Medicine, Kangwon National University, Chuncheon 200-701 (Korea, Republic of); Park, Jinseu [Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chunchon 200-702 (Korea, Republic of); Eum, Won Sik, E-mail: wseum@hallym.ac.kr [Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chunchon 200-702 (Korea, Republic of); Choi, Soo Young, E-mail: sychoi@hallym.ac.kr [Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chunchon 200-702 (Korea, Republic of)

    2012-01-20

    Highlights: Black-Right-Pointing-Pointer We construct a cell permeable Tat-ANX1 fusion protein. Black-Right-Pointing-Pointer We examined the protective effects of Tat-ANX1 protein on OVA-induced asthma in animal models. Black-Right-Pointing-Pointer Transduced Tat-ANX1 protein protects from the OVA-induced production of cytokines and eosinophils in BAL fluid. Black-Right-Pointing-Pointer Tat-ANX1 protein markedly reduced OVA-induced MAPK in lung tissues. Black-Right-Pointing-Pointer Tat-ANX1 protein could be useful as a therapeutic agent for lung disorders including asthma. -- Abstract: Chronic airway inflammation is a key feature of bronchial asthma. Annexin-1 (ANX1) is an anti-inflammatory protein that is an important modulator and plays a key role in inflammation. Although the precise action of ANX1 remains unclear, it has emerged as a potential drug target for inflammatory diseases such as asthma. To examine the protective effects of ANX1 protein on ovalbumin (OVA)-induced asthma in animal models, we used a cell-permeable Tat-ANX1 protein. Mice sensitized and challenged with OVA antigen had an increased amount of cytokines and eosinophils in their bronchoalveolar lavage (BAL) fluid. However, administration of Tat-ANX1 protein before OVA challenge significantly decreased the levels of cytokines (interleukin (IL)-4, IL-5, and IL-13) and BAL fluid in lung tissues. Furthermore, OVA significantly increased the activation of mitogen-activated protein kinase (MAPK) in lung tissues, whereas Tat-ANX1 protein markedly reduced phosphorylation of MAPKs such as extracellular signal-regulated protein kinase, p38, and stress-activated protein kinase/c-Jun N-terminal kinase. These results suggest that transduced Tat-ANX1 protein may be a potential protein therapeutic agent for the treatment of lung disorders including asthma.

  19. Dioscin and methylprotodioscin isolated from the root of Asparagus cochinchinensis suppressed the gene expression and production of airway MUC5AC mucin induced by phorbol ester and growth factor.

    Science.gov (United States)

    Lee, Hyun Jae; Park, Jin Sung; Yoon, Yong Pill; Shin, Ye Jin; Lee, Sang Kook; Kim, Yeong Shik; Hong, Jang-Hee; Son, Kun Ho; Lee, Choong Jae

    2015-05-15

    The root of Asparagus cochinchinensis (Lour.) Merr. has been utilized as mucoregulators and expectorants for controlling the airway inflammatory diseases in folk medicine. We investigated whether dioscin and methylprotodioscin isolated from the root of Asparagus cochinchinensis (Lour.) Merr. suppress the gene expression and production of airway MUC5AC mucin induced by phorbol ester and growth factor. Confluent NCI-H292 cells were pretreated with dioscin or methylprotodioscin for 30 min and then stimulated with EGF or PMA for 24 h. The MUC5AC mucin gene expression was measured by RT-PCR. Production of MUC5AC mucin protein was measured by ELISA. (1) Dioscin and methylprotodioscin suppressed the expression of MUC5AC mucin gene induced by EGF or PMA; (2) dioscin suppressed the production of MUC5AC mucin induced by either EGF at 10(-5) M (p production of MUC5AC mucin induced by either EGF at 10(-4) M (p Asparagus cochinchinensis suppress the gene expression and production of MUC5AC mucin, by directly acting on airway epithelial cells, and the results are consistent with the traditional use of Asparagus cochinchinensis as remedy for diverse inflammatory pulmonary diseases. Copyright © 2015 Elsevier GmbH. All rights reserved.

  20. Bradykinin augments EGF-induced airway smooth muscle proliferation by activation of conventional protein kinase C isoenzymes

    NARCIS (Netherlands)

    Gosens, R; Bromhaar, MMG; Maarsingh, H; ten Damme, A; Meurs, H; Zaagsma, J; Nelemans, SA

    2006-01-01

    This study aims to investigate the effects of bradykinin, alone and in combination with growth factors on proliferation of cultured bovine tracheal smooth muscle cells. Bradykinin did not induce mitogenic responses by itself, but concentration-dependently augmented growth factor-induced [H-3]thymidi

  1. Effect of fenoterol-induced constitutive beta(2)-adrenoceptor activity on contractile receptor function in airway smooth muscle

    NARCIS (Netherlands)

    de Vries, B; Roffel, AF; Zaagsma, J; Meurs, H

    2001-01-01

    In the present study, we investigated the effect of fenoterol-induced constitutive beta (2)-adrenoceptor activity on muscarinic receptor agonist- and histamine-induced bovine tracheal smooth muscle contractions. Bovine tracheal smooth muscle strips were incubated with 10 muM fenoterol or vehicle for

  2. Cuffed oropharyngeal airway for difficult airway management.

    Science.gov (United States)

    Takaishi, Kazumi; Kawahito, Shinji; Tomioka, Shigemasa; Eguchi, Satoru; Kitahata, Hiroshi

    2014-01-01

    Difficulties with airway management are often caused by anatomic abnormalities due to previous oral surgery. We performed general anesthesia for a patient who had undergone several operations such as hemisection of the mandible and reconstructive surgery with a deltopectoralis flap, resulting in severe maxillofacial deformation. This made it impossible to ventilate with a face mask and to intubate in the normal way. An attempt at oral awake intubation using fiberoptic bronchoscopy was unsuccessful because of severe anatomical abnormality of the neck. We therefore decided to perform retrograde intubation and selected the cuffed oropharyngeal airway (COPA) for airway management. We inserted the COPA, not through the patient's mouth but through the abnormal oropharyngeal space. Retrograde nasal intubation was accomplished with controlled ventilation through the COPA, which proved to be very useful for this difficult airway management during tracheal intubation even though the method was unusual.

  3. Estimation of airway obstruction using oximeter plethysmograph waveform data

    Directory of Open Access Journals (Sweden)

    Desmond Renee' A

    2005-06-01

    Full Text Available Abstract Background Validated measures to assess the severity of airway obstruction in patients with obstructive airway disease are limited. Changes in the pulse oximeter plethysmograph waveform represent fluctuations in arterial flow. Analysis of these fluctuations might be useful clinically if they represent physiologic perturbations resulting from airway obstruction. We tested the hypothesis that the severity of airway obstruction could be estimated using plethysmograph waveform data. Methods Using a closed airway circuit with adjustable inspiratory and expiratory pressure relief valves, airway obstruction was induced in a prospective convenience sample of 31 healthy adult subjects. Maximal change in airway pressure at the mouthpiece was used as a surrogate measure of the degree of obstruction applied. Plethysmograph waveform data and mouthpiece airway pressure were acquired for 60 seconds at increasing levels of inspiratory and expiratory obstruction. At each level of applied obstruction, mean values for maximal change in waveform area under the curve and height as well as maximal change in mouth pressure were calculated for sequential 7.5 second intervals. Correlations of these waveform variables with mouth pressure values were then performed to determine if the magnitude of changes in these variables indicates the severity of airway obstruction. Results There were significant relationships between maximal change in area under the curve (P Conclusion The findings suggest that mathematic interpretation of plethysmograph waveform data may estimate the severity of airway obstruction and be of clinical utility in objective assessment of patients with obstructive airway diseases.

  4. Prolonged cigarette smoke exposure alters mitochondrial structure and function in airway epithelial cells

    NARCIS (Netherlands)

    Hoffmann, Roland F.; Zarrintan, Sina; Brandenburg, Simone M.; Kol, Arjan; de Bruin, Harold G.; Jafari, Shabnam; Dijk, Freark; Kalicharan, Dharamdajal; Kelders, Marco; Gosker, Harry R.; ten Hacken, Nick H. T.; van der Want, Johannes J.; van Oosterhout, Antoon J. M.; Heijink, Irene H.

    2013-01-01

    Background: Cigarette smoking is the major risk factor for COPD, leading to chronic airway inflammation. We hypothesized that cigarette smoke induces structural and functional changes of airway epithelial mitochondria, with important implications for lung inflammation and COPD pathogenesis. Methods:

  5. Prolonged cigarette smoke exposure alters mitochondrial structure and function in airway epithelial cells

    NARCIS (Netherlands)

    Hoffmann, Roland F; Zarrintan, Sina; Brandenburg, Simone M; Kol, Arjan; de Bruin, Harold G; Jafari, Shabnam; Dijk, Freark; Kalicharan, Dharamdajal; Kelders, Marco; Gosker, Harry R; Ten Hacken, Nick Ht; van der Want, Johannes J; van Oosterhout, Antoon Jm; Heijink, Irene H

    2013-01-01

    BACKGROUND: Cigarette smoking is the major risk factor for COPD, leading to chronic airway inflammation. We hypothesized that cigarette smoke induces structural and functional changes of airway epithelial mitochondria, with important implications for lung inflammation and COPD pathogenesis. METHODS:

  6. 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.

  7. Hyperplasia and hypertrophy of pulmonary neuroepithelial bodies, presumed airway hypoxia sensors, in hypoxia-inducible factor prolyl hydroxylase-deficient mice.

    Science.gov (United States)

    Pan, Jie; Bishop, Tammie; Ratcliffe, Peter J; Yeger, Herman; Cutz, Ernest

    2016-01-01

    Pulmonary neuroepithelial bodies (NEBs), presumed polymodal airway sensors, consist of innervated clusters of amine (serotonin) and peptide-producing cells. While NEB responses to acute hypoxia are mediated by a membrane-bound O2 sensor complex, responses to sustained and/or chronic hypoxia involve a prolyl hydroxylase (PHD)-hypoxia-inducible factor-dependent mechanism. We have previously reported hyperplasia of NEBs in the lungs of Phd1-/- mice associated with enhanced serotonin secretion. Here we use a novel multilabel immunofluorescence method to assess NEB distribution, frequency, and size, together with the number and size of NEB cell nuclei, and to colocalize multiple cytoplasmic and nuclear epitopes in the lungs of Phd1-/-, Phd2+/-, and Phd3-/- mice and compare them with wild-type controls. To define the mechanisms of NEB cell hyperplasia, we used antibodies against Mash1 and Prox1 (neurogenic genes involved in NEB cell differentiation/maturation), hypoxia-inducible factor-1alpha, and the cell proliferation marker Ki67. Morphometric analysis of (% total lung area) immunostaining for synaptophysin (% synaptophysin), a cytoplasmic marker of NEB cells, was significantly increased in Phd1-/- and Phd3-/- mice compared to wild-type mice. In addition, NEB size and the number and size of NEB nuclei were also significantly increased, indicating that deficiency of Phds is associated with striking hyperplasia and hypertrophy of NEBs. In Phd2+/- mice, while mean % synaptophysin was comparable to wild-type controls, the NEB size was moderately increased, suggesting an effect even in heterozygotes. NEBs in all Phd-deficient mice showed increased expression of Mash1, Prox1, Ki67, and hypoxia-inducible factor-1alpha, in keeping with enhanced differentiation from precursor cells and a minor component of cell proliferation. Since the loss of PHD activity mimics chronic hypoxia, our data provide critical information on the potential role of PHDs in the pathobiology and

  8. [Role of phosphorylation of MARCKS-PSD in the secretion of MUC5AC induced by cold temperatures in human airway epithelial cells].

    Science.gov (United States)

    Li, Minchao; Perelman, Juliy M; Zhou, Xiangdong

    2012-05-01

    To construct phosphorylation sites domain (PSD) mutant of myristoylated alaninerich C kinase substrate (MARCKS) and explore the role of transient receptor potential melastatin 8 cation channels (TRPM8) and MARCKS in cold-induced synthesis and exocytosis of mucin (MUC) 5AC. Human placental cDNA was used as a template to amplify the full coding region of MARCKS cDNA by PCR. Ser159, Ser 163, Ser 167, Ser 170 in the PSD were mutated to aspartic acids by an overlap PCR method. The resultant PSD mutant cDNA and the wild-type MARCKS cDNA were each subcloned into a mammalian expression vector pcDNA3.0. Recombinant constructs were confirmed by restriction enzyme digestion analysis and DNA sequencing. In intervention experiments, cells were pretreated with the TRPM8 channel antagonist BCTC and transfected with MARCKS-PSD mutant cDNA, and thereafter cold stimulation was applied. The levels of MUC5AC were measured by immunofluorescence and ELISA to clarify the roles of TRPM8 and PSD mutant on the synthesis and secretion of MUC5AC induced by cold, respectively. Restriction enzyme digestion analysis and DNA sequencing revealed that the pcDNA3.0- MARCKS and pcDNA3.0-MARCKS-PSD mutants were successfully constructed. The levels of intracellular and secreted MUC5AC of cold treated group were significantly higher than those of control group (PPSD mutant cDNA resulted in significant inhibition of mucin secretion in response to cold, and significantly higher level of intracellular MUC5AC than that of control group (P0.05). TRPM8 and phosphorylation of MARCKS-PSD mediates the cold-induced exocytosis of MUC5AC by airway epithelial cells.

  9. A comparison of desflurane and sevoflurane in the recovery of cognitive function after general anesthesia in elderly patients

    Directory of Open Access Journals (Sweden)

    Pandurang Kondiba Jadhav

    2015-11-01

    Full Text Available Background: The postoperative cognitive dysfunction (POCD or psychomotor function disorder is known to be associated with the anesthetic agents, as well as the physiological changes resulting from the anesthesia. The known risk factors are old age, preexisting cerebral cardiac or vascular disease, alcohol abuse, intra and post-operative complications. Methods: 50 patients above 65 years of age falling into ASA Grade 1, 2, or 3 were catagrzed into 2 groups, one (Group A wherein sevoflurane was given as the anesthetic agent and the other (Group B where desflurane was administered. All had undergone physical and regular blood examination. MMSE score was taken for all patients for cognitive recognition before surgery and 1, 3, and 6 hours after surgery. Results: Of the 50 patients, the MMSE score was above 27 for all before surgery, while, post-surgery it was below 27 after I hour in 100% of the cases. After 3 hours, in Group A, the mean MMSE was above 27 while it was still below 27 in Group B while it was above 27 in both the Groups after 6 hours post-surgery. There was only 1 cases of POCD after 6 hours in Group A and none in Group B. The recovery time was faster in Group B as compared to Group A. Conclusions: Desflurane was marginally a better anesthetic agent in terms or recovery to sevoflurane and sevoflurane was slightly better than the former when it came to cognitive recognition Therefore, we conclude that both the drugs are equally good anesthetic agents. [Int J Res Med Sci 2015; 3(11.000: 3278-3282

  10. Engineering Airway Epithelium

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    John P. Soleas

    2012-01-01

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

  11. Neutrophil Inhibitory Factor Selectively Inhibits the Endothelium-Driven Transmigration of Eosinophils In Vitro and Airway Eosinophilia in OVA-Induced Allergic Lung Inflammation

    Directory of Open Access Journals (Sweden)

    Silvia Schnyder-Candrian

    2012-01-01

    Full Text Available Leukocyte adhesion molecules are involved in cell recruitment in an allergic airway response and therefore provide a target for pharmaceutical intervention. Neutrophil inhibitory factor (NIF, derived from canine hookworm (Ancylostoma caninum, binds selectively and competes with the A-domain of CD11b for binding to ICAM-1. The effect of recombinant NIF was investigated. Intranasal administration of rNIF reduced pulmonary eosinophilic infiltration, goblet cell hyperplasia, and Th2 cytokine production in OVA-sensitized mice. In vitro, transendothelial migration of human blood eosinophils across IL-4-activated umbilical vein endothelial cell (HUVEC monolayers was inhibited by rNIF (IC50: 4.6±2.6 nM; mean ± SEM, but not across TNF or IL-1-activated HUVEC monolayers. Treatment of eosinophils with rNIF together with mAb 60.1 directed against CD11b or mAb 107 directed against the metal ion-dependent adhesion site (MIDAS of the CD11b A-domain resulted in no further inhibition of transendothelial migration suggesting shared functional epitopes. In contrast, rNIF increased the inhibitory effect of blocking mAbs against CD18, CD11a, and VLA-4. Together, we show that rNIF, a selective antagonist of the A-domain of CD11b, has a prominent inhibitory effect on eosinophil transendothelial migration in vitro, which is congruent to the in vivo inhibition of OVA-induced allergic lung inflammation.

  12. [Regeneration of airway epithelium].

    Science.gov (United States)

    Adam, D; Perotin, J-M; Lebargy, F; Birembaut, P; Deslée, G; Coraux, C

    2014-04-01

    Epithelial regeneration is a complex process. It can lead to the remodeling of the airway epithelium as in asthma, COPD or cystic fibrosis. The development of in vivo and in vitro models has allowed the analysis of remodeling mechanisms and showed the role of components of extracellular matrix, proteases, cytokines and growth factors. Airway epithelial progenitors and stems cells have been studied in these models. However, their identification remains difficult. Identification and characterization of airway epithelial progenitor/stem-cells, and a better knowledge of the regeneration process may allow the development of new therapeutic strategies for airway epithelial reconstitution. Copyright © 2013 SPLF. Published by Elsevier Masson SAS. All rights reserved.

  13. Airway management in trauma

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    Rao B

    2004-01-01

    Full Text Available Airway Management for the victims of major trauma is the first priority in the care of the trauma victim and is a core skill in emergency medicine and critical care. Endotracheal intubation remains the gold standard for trauma airway management. Airway management in trauma patients is not just the capability to insert an oral/nasal airway or endotracheal tube beyond the vocal cords. The five components integral to modern, sophisticated airway management in trauma patients include equipment, pharmacologic adjuncts, manual techniques, physical circumstances, and patient profile. A trauma patient may require airway management in a variety of physical circumstances. Whereas, the commonly used airway management algorithms may not suffice in all these situations, the construction of a truly complete decision tree is also virtually impossible. There is consensus that it is not the intervention per se but rather the conditions, skills, and performance that might be the possible variables that affect outcome. Paramedics have only limited experience and on-the-job skills for invasive airway management. Difficult airway management is best left for the experienced physicians to handle.

  14. Evaluation of pharmacological relaxation effect of the natural product naringin on in vitro cultured airway smooth muscle cells and in vivo ovalbumin-induced asthma Balb/c mice

    Science.gov (United States)

    Wang, Yue; Lu, Yun; Luo, Mingzhi; Shi, Xiaohao; Pan, Yan; Zeng, Huilong; Deng, Linhong

    2016-01-01

    Asthma has become a common chronic respiratory disease worldwide and its prevalence is predicted to continue increasing in the next decade, particularly in developing countries. A key component in asthma therapy is to alleviate the excessive bronchial airway narrowing ultimately due to airway smooth muscle contraction, which is often facilitated by a smooth muscle relaxant, such as the β2-adrenergic agonists. Recently, bitter taste receptor (TAS2R) agonists, including saccharin and chloroquine, have been found to potently relax the airway smooth muscle cells (ASMCs) via intracellular Ca2+ signaling. This inspires a great interest in screening the vast resource of natural bitter substances for potential bronchodilatory drugs. In the present study, the relaxation effect of naringin, a compound extracted from common grapefruit, on ASMCs cultured in vitro or bronchial airways of Balb/c mice in vivo was evaluated. The results demonstrated that, when exposed to increasing doses of naringin (0.125, 0.25, 0.5 and 1.0 mM), the traction force generated by the cultured ASMCs decreased progressively, while the intracellular calcium flux signaling in the ASMCs increased. When inhaled at increasing doses (15, 30 and 60 µg), naringin also dose-dependently reduced the bronchial airway resistance of the normal and ovalbumin-induced asthma Balb/c mice in response to challenge with methacholine. In conclusion, these findings indicate that naringin was able to effectively relax murine ASMCs in vitro and in vivo, thus suggesting that it is a promising drug agent to be further investigated in the development of novel bronchodilators for the treatment of asthma. PMID:28101344

  15. Blockade of Airway Inflammation by Kaempferol via Disturbing Tyk-STAT Signaling in Airway Epithelial Cells and in Asthmatic Mice

    OpenAIRE

    Ju-Hyun Gong; Daekeun Shin; Seon-Young Han; Sin-Hye Park; Min-Kyung Kang; Jung-Lye Kim; Young-Hee Kang

    2013-01-01

    Asthma is characterized by bronchial inflammation causing increased airway hyperresponsiveness and eosinophilia. The interaction between airway epithelium and inflammatory mediators plays a key role in the asthmatic pathogenesis. The in vitro study elucidated inhibitory effects of kaempferol, a flavonoid found in apples and many berries, on inflammation in human airway epithelial BEAS-2B cells. Nontoxic kaempferol at ≤20  μ M suppressed the LPS-induced IL-8 production through the TLR4 activat...

  16. Anti-Inflammatory Activity of a Novel Family of Aryl Ureas Compounds in an Endotoxin-Induced Airway Epithelial Cell Injury Model

    Science.gov (United States)

    Cabrera-Benitez, Nuria E.; Pérez-Roth, Eduardo; Casula, Milena; Ramos-Nuez, Ángela; Ríos-Luci, Carla; Rodríguez-Gallego, Carlos; Sologuren, Ithaisa; Jakubkiene, Virginija; Slutsky, Arthur S.; Padrón, José M.; Villar, Jesús

    2012-01-01

    Background Despite our increased understanding of the mechanisms involved in acute lung injury (ALI) and the acute respiratory distress syndrome (ARDS), there is no specific pharmacological treatment of proven benefit. We used a novel screening methodology to examine potential anti-inflammatory effects of a small structure-focused library of synthetic carbamate and urea derivatives in a well established cell model of lipopolysaccharide (LPS)-induced ALI/ARDS. Methodology/Principal Findings After a pilot study to develop an in vitro LPS-induced airway epithelial cell injury model, a library of synthetic carbamate and urea derivates was screened against representative panels of human solid tumor cell lines and bacterial and fungal strains. Molecules that were non-cytotoxic and were inactive in terms of antiproliferative and antimicrobial activities were selected to study the effects on LPS-induced inflammatory response in an in vitro cell culture model using A549 human alveolar and BEAS-2B human bronchial cells. These cells were exposed for 18 h to LPS obtained from Escherichia coli, either alone or in combination with the test compounds. The LPS antagonists rhein and emodin were used as reference compounds. The most active compound (CKT0103) was selected as the lead compound and the impact of CKT0103 on pro-inflammatory IL-6 and IL-8 cytokine levels, expression of toll-like receptor-4 (TLR4) and nuclear factor kappa B inhibitor alpha (IκBα) was measured. CKT0103 significantly inhibited the synthesis and release of IL-6 and IL-8 induced by LPS. This suppression was associated with inhibition of TLR4 up-regulation and IκBα down-regulation. Immunocytochemical staining for TLR4 and IκBα supported these findings. Conclusions/Significance Using a novel screening methodology, we identified a compound – CKT0103 – with potent anti-inflammatory effects. These findings suggest that CKT0103 is a potential target for the treatment of the acute phase of sepsis and

  17. Anti-inflammatory activity of a novel family of aryl ureas compounds in an endotoxin-induced airway epithelial cell injury model.

    Directory of Open Access Journals (Sweden)

    Nuria E Cabrera-Benitez

    Full Text Available BACKGROUND: Despite our increased understanding of the mechanisms involved in acute lung injury (ALI and the acute respiratory distress syndrome (ARDS, there is no specific pharmacological treatment of proven benefit. We used a novel screening methodology to examine potential anti-inflammatory effects of a small structure-focused library of synthetic carbamate and urea derivatives in a well established cell model of lipopolysaccharide (LPS-induced ALI/ARDS. METHODOLOGY/PRINCIPAL FINDINGS: After a pilot study to develop an in vitro LPS-induced airway epithelial cell injury model, a library of synthetic carbamate and urea derivates was screened against representative panels of human solid tumor cell lines and bacterial and fungal strains. Molecules that were non-cytotoxic and were inactive in terms of antiproliferative and antimicrobial activities were selected to study the effects on LPS-induced inflammatory response in an in vitro cell culture model using A549 human alveolar and BEAS-2B human bronchial cells. These cells were exposed for 18 h to LPS obtained from Escherichia coli, either alone or in combination with the test compounds. The LPS antagonists rhein and emodin were used as reference compounds. The most active compound (CKT0103 was selected as the lead compound and the impact of CKT0103 on pro-inflammatory IL-6 and IL-8 cytokine levels, expression of toll-like receptor-4 (TLR4 and nuclear factor kappa B inhibitor alpha (IκBα was measured. CKT0103 significantly inhibited the synthesis and release of IL-6 and IL-8 induced by LPS. This suppression was associated with inhibition of TLR4 up-regulation and IκBα down-regulation. Immunocytochemical staining for TLR4 and IκBα supported these findings. CONCLUSIONS/SIGNIFICANCE: Using a novel screening methodology, we identified a compound - CKT0103 - with potent anti-inflammatory effects. These findings suggest that CKT0103 is a potential target for the treatment of the acute phase of

  18. Silibinin attenuates allergic airway inflammation in mice

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Yun Ho [Department of Anatomy, Medical School, Institute for Medical Sciences, Chonbuk National University, Jeonju, Jeonbuk 561-756 (Korea, Republic of); Jin, Guang Yu [Department of Radiology, Yanbian University Hospital, YanJi 133002 (China); Guo, Hui Shu [Centralab, The First Affiliated Hospital of Dalian Medical University, Dalian 116011 (China); Piao, Hong Mei [Department of Respiratory Medicine, Yanbian University Hospital, YanJi 133000 (China); Li, Liang chang; Li, Guang Zhao [Department of Anatomy and Histology and Embryology, Yanbian University School of Basic Medical Sciences, 977 Gongyuan Road, YanJi 133002, Jilin (China); Lin, Zhen Hua [Department of Pathology, Yanbian University School of Basic Medical Sciences, YanJi 133000 (China); Yan, Guang Hai, E-mail: ghyan@ybu.edu.cn [Department of Anatomy and Histology and Embryology, Yanbian University School of Basic Medical Sciences, 977 Gongyuan Road, YanJi 133002, Jilin (China)

    2012-10-26

    Highlights: Black-Right-Pointing-Pointer Silibinin diminishes ovalbumin-induced inflammatory reactions in the mouse lung. Black-Right-Pointing-Pointer Silibinin reduces the levels of various cytokines into the lung of allergic mice. Black-Right-Pointing-Pointer Silibinin prevents the development of airway hyperresponsiveness in allergic mice. Black-Right-Pointing-Pointer Silibinin suppresses NF-{kappa}B transcriptional activity. -- Abstract: Allergic asthma is a chronic inflammatory disease regulated by coordination of T-helper2 (Th2) type cytokines and inflammatory signal molecules. Silibinin is one of the main flavonoids produced by milk thistle, which is reported to inhibit the inflammatory response by suppressing the nuclear factor-kappa B (NF-{kappa}B) pathway. Because NF-{kappa}B activation plays a pivotal role in the pathogenesis of allergic inflammation, we have investigated the effect of silibinin on a mouse ovalbumin (OVA)-induced asthma model. Airway hyperresponsiveness, cytokines levels, and eosinophilic infiltration were analyzed in bronchoalveolar lavage fluid and lung tissue. Pretreatment of silibinin significantly inhibited airway inflammatory cell recruitment and peribronchiolar inflammation and reduced the production of various cytokines in bronchoalveolar fluid. In addition, silibinin prevented the development of airway hyperresponsiveness and attenuated the OVA challenge-induced NF-{kappa}B activation. These findings indicate that silibinin protects against OVA-induced airway inflammation, at least in part via downregulation of NF-{kappa}B activity. Our data support the utility of silibinin as a potential medicine for the treatment of asthma.

  19. DNA vaccine encoding Der p2 allergen down-regulates STAT6 expression in mouse model of allergen-induced allergic airway inflammation

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Background Activation of signal transducer and activator of transcription 6 (STAT6 ) plays a critical role in the late phase of Th2-dependent allergy induction. STAT6 is essential to Th2 cell differentiation, recruitment, and effector function. Our previous study confirmed that DNA vaccination inhibited STAT6 expression of spleen cells induced by allergen. In the present study, we determined whether DNA vaccine encoding Dermatophagoides pteronyssinus group 2 (Der p2 ) could down-regulate the expression and activation of STAT6 in lung tissue from asthmatic mice.Methods After DNA vaccine immunization, BALB/c mice were sensitized by intraperitoneal injection and challenged by intranasal instillation of rDer p2. The levels of the cytokines IL-4 and IL-13 in BAL fluid were measured by enzyme-linked immunosorbent assay. The lung tissue was assessed by immunohistochemical staining with anti-STAT6. The protein expression of STAT6 was determined by Western blot. The activation of STAT6 binding ability was analyzed with electrophoretic mobility shift assay.Results DNA vaccine encoding Der p2 allergen effectively decreased the levels of IL-4 and IL-13 in the asthmatic mice. Histological evidence and Western blot showed that the expression of STAT6 in the DNA treated mice was markedly attenuated. STAT6 binding to specific DNA motif in lung tissue from the gene vaccinated mice was inhibited.Conclusion DNA vaccine encoding Der p2 prevents allergic pulmonary inflammation probably by inhibiting the STAT6 signaling pathway in mice with Der p2 allergen-induced allergic airway inflammation.

  20. Matrix metalloprotease 9 mediates neutrophil migration into the airways in response to influenza virus-induced toll-like receptor signaling.

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    Linda M Bradley

    Full Text Available The early inflammatory response to influenza virus infection contributes to severe lung disease and continues to pose a serious threat to human health. The mechanisms by which neutrophils gain entry to the respiratory tract and their role during pathogenesis remain unclear. Here, we report that neutrophils significantly contributed to morbidity in a pathological mouse model of influenza virus infection. Using extensive immunohistochemistry, bone marrow transfers, and depletion studies, we identified neutrophils as the predominant pulmonary cellular source of the gelatinase matrix metalloprotease (MMP 9, which is capable of digesting the extracellular matrix. Furthermore, infection of MMP9-deficient mice showed that MMP9 was functionally required for neutrophil migration and control of viral replication in the respiratory tract. Although MMP9 release was toll-like receptor (TLR signaling-dependent, MyD88-mediated signals in non-hematopoietic cells, rather than neutrophil TLRs themselves, were important for neutrophil migration. These results were extended using multiplex analyses of inflammatory mediators to show that neutrophil chemotactic factor, CCL3, and TNFα were reduced in the Myd88⁻/⁻ airways. Furthermore, TNFα induced MMP9 secretion by neutrophils and blocking TNFα in vivo reduced neutrophil recruitment after infection. Innate recognition of influenza virus therefore provides the mechanisms to induce recruitment of neutrophils through chemokines and to enable their motility within the tissue via MMP9-mediated cleavage of the basement membrane. Our results demonstrate a previously unknown contribution of MMP9 to influenza virus pathogenesis by mediating excessive neutrophil migration into the respiratory tract in response to viral replication that could be exploited for therapeutic purposes.

  1. ß2-adrenoceptor agonist-induced upregulation of tachykinin NK2 receptor expression and function in airway smooth muscle

    NARCIS (Netherlands)

    Katsunuma, T; Roffel, A.F; Elzinga, C.R S; Zaagsma, Hans; Barnes, P.J; Mak, J.CW

    Neurokinin A (NKA) induces bronchoconstriction mediated by tachykinin NK2 receptors in animals and humans, and may be increased in asthma. Because beta(2)-adrenoceptor agonists are the most widely used bronchodilators in asthma, we investigated the effects of the beta(2)-adrenoceptor agonist

  2. The Role of Lipid Hydroperoxides in Ozone-Induced Increases in Glutathione Redox Potential in Human Airway Epithelial Cells

    Science.gov (United States)

    Human exposure to tropospheric ozone pollution is of global public health concern. Exposure to ozone induces functional decrements and inflammatory responses in the respiratory tract that are thought to occur through oxidative mechanisms. While it is known that ozone oxidizes p...

  3. Salbutamol pMDI gives less protection to methacholine induced airway obstruction than salbutamol via spacer or DPI.

    NARCIS (Netherlands)

    Broeders, M.E.A.C.; Molema, J.; Hop, W.C.J.; Folgering, H.T.M.

    2005-01-01

    BACKGROUND: Inhalation device and inhalation technique influence the deposition of drug in the lung. This study evaluated the efficacy of salbutamol as a bronchoprotective agent administered via Diskus, Turbuhaler, pMDI or pMDI + Volumatic against methacholine-induced bronchoconstriction. METHODS: T

  4. The Effects of Bispectral Index and Neuromuscular Blockade Monitoring on the Depth of Anaesthesia and Recovery in Cardiac Patients Under Desflurane Anaesthesia

    Science.gov (United States)

    Payas, Ayşe; Kaygusuz, Kenan; Düger, Cevdet; İsbir, Ahmet Cemil; Kol, İclal Özdemir; Gürsoy, Sinan; Mimaroğlu, Caner

    2013-01-01

    Objective In this study, we aimed to investigate the effects of bispectral index (BIS) and neuromuscular blockade monitoring on the depth of anaesthesia and recovery in cardiac patients, scheduled to undergo open cholecystectomy operation with desflurane anaesthesia. Methods After the approval of the Ethics Committee and consent from the patients, patients were randomly divided into two groups. All patients received standard induction drugs, and 4–6% desflurane was used for maintenance of anaesthesia. In Group I, the anaesthesiologist was blind to BIS, and end-tidal volatile agent concentration (ETVAC) of desflurane was titrated according to the patients’ hemodynamic changes. In Group II, ETVAC of desflurane was titrated to maintain BIS at 50–60. The hemodynamic data, BIS values, end-tidal volatile agent concentration (ETVAC) and train of four (TOF) values were recorded at pre-induction, post-induction, post-intubation, 1st and 5th minutes after surgical incision and then every 15 min. At the end of the operation, extubation time and the time to reach an Aldrete recovery score ≥9 were recorded in each group. Additionally, neuromuscular agent and narcotic agent doses were recorded. Results The BIS values were lower for Group I in all times, except pre- and post-induction times (p<0.05). ETVAC values of all times were lower for Group II (p<0.05). Conclusion The requirement of volatile agent, which was given according to BIS monitoring, was lower than in the standard technique, but it is considered not to affect the early extubation, recovery and neuromuscular agent requirement dependent on TOF monitoring. PMID:27366374

  5. Effect of desflurane-remifentanil vs. Propofol-remifentanil anesthesia on arterial oxygenation during one-lung ventilation for thoracoscopic surgery: a prospective randomized trial

    OpenAIRE

    Cho, Youn Joung; Kim, Tae Kyong; Hong, Deok Man; Seo, Jeong-Hwa; Bahk, Jae-Hyon; Jeon, Yunseok

    2017-01-01

    Background One-lung ventilation during thoracic surgery frequently disturbs normal systemic oxygenation. However, the effect of anesthetics on arterial oxygenation during one-lung ventilation has not been well established in human study. In this clinical trial, we investigated whether a difference between desflurane-remifentanil and propofol-remifentanil anesthesia can be observed with regard to oxygenation during one-lung ventilation for thoracoscopic surgery. Methods Adult patients with lun...

  6. Interleukin-13 induces collagen type-1 expression through matrix metalloproteinase-2 and transforming growth factor-β1 in airway fibroblasts in asthma.

    Science.gov (United States)

    Firszt, Rafael; Francisco, Dave; Church, Tony D; Thomas, Joseph M; Ingram, Jennifer L; Kraft, Monica

    2014-02-01

    Airway remodelling is a feature of asthma that contributes to loss of lung function. One of the central components of airway remodelling is subepithelial fibrosis. Interleukin (IL)-13 is a key T-helper 2 cytokine and is believed to be the central mediator of allergic asthma including remodelling, but the mechanism driving the latter has not been elucidated in human asthma. We hypothesised that IL-13 stimulates collagen type-1 production by the airway fibroblast in a matrix metalloproteinase (MMP)- and transforming growth factor (TGF)-β1-dependent manner in human asthma as compared to healthy controls. Fibroblasts were cultured from endobronchial biopsies in 14 subjects with mild asthma and 13 normal controls that underwent bronchoscopy. Airway fibroblasts were treated with various mediators including IL-13 and specific MMP-inhibitors. IL-13 significantly stimulated collagen type-1 production in asthma compared to normal controls. Inhibitors of MMP-2 significantly attenuated collagen production in asthma but had no effect in normal controls. IL-13 significantly increased total and active forms of TGF-β1, and this activation was blocked using an MMP-2 inhibitor. IL-13 activated endogenous MMP-2 in asthma patients as compared to normal controls. In an ex vivo model, IL-13 potentiates airway remodelling through a mechanism involving TGF-β1 and MMP-2. These effects provide insights into the mechanism involved in IL-13-directed airway remodelling in asthma.

  7. Essentials of airway management, oxygenation, and ventilation: part 2: advanced airway devices: supraglottic airways

    National Research Council Canada - National Science Library

    Rosenberg, M B; Phero, J C; Becker, D E

    2014-01-01

    .... This article will review the evolution and use of advanced airway devices, specifically supraglottic airways, with the emphasis on the laryngeal mask airway, as the next intervention in difficult...

  8. Comparison of TIVA and Desflurane Added to a Subanaesthetic Dose of Propofol in Patients Undergoing Coronary Artery Bypass Surgery: Evaluation of Haemodynamic and Stress Hormone Changes

    Directory of Open Access Journals (Sweden)

    Didem Onk

    2016-01-01

    Full Text Available Introduction. Increased levels of stress hormones are associated with mortality in patients undergoing coronary artery bypass grafting (CABG. Aim. To compare total intravenous anaesthesia (TIVA and desflurane added to a subanaesthetic dose of propofol. Material and Methods. Fifty patients were enrolled in this study. Fentanyl (3–5 mcg/kg/h was started in both groups. Patients were divided into two groups. The PD group (n=25 received 1 minimum alveolar concentration (MAC desflurane anaesthesia in addition to propofol infusion (2-3 mg/kg/h, while P group (n=25 received propofol infusion (5-6 mg/kg/h only. Biochemical data, cortisol, and insulin levels were measured preoperatively (T0, after initiation of CPB but before cross-clamping the aorta (T1, after removal of the cross-clamp (T2, and at the 24th postoperative hour (T3. Results. Systolic, diastolic, and mean arterial pressure levels were significantly higher in PD group than those in P group in T1 and T2 measurements (p≤0.05. CK-MB showed a significant decrease in group P (p≤0.05. When we compared both groups, cortisol levels were significantly higher in PD group than P group (p≤0.05. Conclusion. Stress and haemodynamic responses were better controlled using TIVA than desflurane inhalation added to a subanaesthetic dose of propofol in patients undergoing CABG.

  9. Warm SPA-induced hyperthermia confers protection to rats against airway inflammation evoked by capsaicin and substance P.

    Science.gov (United States)

    Fu, Yaw-Syan; Wang, Peng-Han; Liu, Shang-Pin; Huang, Wen-Hung; Huang, Hung-Tu

    2010-06-24

    Solus par aqua (SPA) is a traditional health care therapy. Warm SPA may enhance immunity and cellular defense to protect body against diseases. The present study investigated whether the warm SPA could confer protection to neurogenic inflammation in rats. The rats were immersed in water where the body core temperatures were maintained at hyperthermia (41.5 degrees C) or normothermia (37 degrees C) for a period of 15min. After SPA for 1 or 6 days, neurogenic inflammation was induced by intravenous injection of capsaicin (90microg/kg) or substance P (SP; 3microg/kg). The plasma leakage and arterial pressures in rats after neurogenic inflammation were monitored. The extent of capsaicin- or SP-induced plasma leakage and hypotension was significantly attenuated in rats on day 1 after SPA hyperthermia. However, such resistance to neurogenic inflammation was not found on day 6 after hyperthermia. Western blotting analysis showed that the expression of heat shock protein 72 (HSP 72) in the trachea on days 1 and 2 after hyperthermia was 9.61-fold and 6.66-fold, respectively, of that in normothermia. Afterwards, the hyperthermia-induced HSP 72 upregulation gradually declined in a time-dependent manner. Thus, SPA hyperthermia may protect rats against neurogenic inflammation through modulation of HSP expression.

  10. CysLT1 receptor-induced human airway smooth muscle cells proliferation requires ROS generation, EGF receptor transactivation and ERK1/2 phosphorylation

    Directory of Open Access Journals (Sweden)

    Capra Valérie

    2006-03-01

    Full Text Available Abstract Background Cysteine-containing leukotrienes (cysteinyl-LTs are pivotal inflammatory mediators that play important roles in the pathophysiology of asthma, allergic rhinitis, and other inflammatory conditions. In particular, cysteinyl-LTs exert a variety of effects with relevance to the aetiology of asthma such as smooth muscle contraction, eosinophil recruitment, increased microvascular permeability, enhanced mucus secretion and decreased mucus transport and, finally, airway smooth muscle cells (ASMC proliferation. We used human ASMC (HASMC to identify the signal transduction pathway(s of the leukotriene D4 (LTD4-induced DNA synthesis. Methods Proliferation of primary HASMC was measured by [3H]thymidine incorporation. Phosphorylation of EGF receptor (EGF-R and ERK1/2 was assessed with a polyclonal anti-EGF-R or anti-phosphoERKl/2 monoclonal antibody. A Ras pull-down assay kit was used to evaluate Ras activation. The production of reactive oxygen species (ROS was estimated by measuring dichlorodihydrofluorescein (DCF oxidation. Results We demonstrate that in HASMC LTD4-stimulated thymidine incorporation and potentiation of EGF-induced mitogenic signaling mostly depends upon EGF-R transactivation through the stimulation of CysLT1-R. Accordingly, we found that LTD4 stimulation was able to trigger the increase of Ras-GTP and, in turn, to activate ERK1/2. We show here that EGF-R transactivation was sensitive to pertussis toxin (PTX and phosphoinositide 3-kinase (PI3K inhibitors and that it occurred independently from Src activity, despite the observation of a strong impairment of LTD4-induced DNA synthesis following Src inhibition. More interestingly, CysLT1-R stimulation increased the production of ROS and N-acetylcysteine (NAC abolished LTD4-induced EGF-R phosphorylation and thymidine incorporation. Conclusion Collectively, our data demonstrate that in HASMC LTD4 stimulation of a Gi/o coupled CysLT1-R triggers the transactivation of the EGF

  11. CysLT1 receptor-induced human airway smooth muscle cells proliferation requires ROS generation, EGF receptor transactivation and ERK1/2 phosphorylation.

    Science.gov (United States)

    Ravasi, Saula; Citro, Simona; Viviani, Barbara; Capra, Valérie; Rovati, G Enrico

    2006-03-22

    Cysteine-containing leukotrienes (cysteinyl-LTs) are pivotal inflammatory mediators that play important roles in the pathophysiology of asthma, allergic rhinitis, and other inflammatory conditions. In particular, cysteinyl-LTs exert a variety of effects with relevance to the aetiology of asthma such as smooth muscle contraction, eosinophil recruitment, increased microvascular permeability, enhanced mucus secretion and decreased mucus transport and, finally, airway smooth muscle cells (ASMC) proliferation. We used human ASMC (HASMC) to identify the signal transduction pathway(s) of the leukotriene D4 (LTD4)-induced DNA synthesis. Proliferation of primary HASMC was measured by [3H]thymidine incorporation. Phosphorylation of EGF receptor (EGF-R) and ERK1/2 was assessed with a polyclonal anti-EGF-R or anti-phosphoERKl/2 monoclonal antibody. A Ras pull-down assay kit was used to evaluate Ras activation. The production of reactive oxygen species (ROS) was estimated by measuring dichlorodihydrofluorescein (DCF) oxidation. We demonstrate that in HASMC LTD4-stimulated thymidine incorporation and potentiation of EGF-induced mitogenic signaling mostly depends upon EGF-R transactivation through the stimulation of CysLT1-R. Accordingly, we found that LTD4 stimulation was able to trigger the increase of Ras-GTP and, in turn, to activate ERK1/2. We show here that EGF-R transactivation was sensitive to pertussis toxin (PTX) and phosphoinositide 3-kinase (PI3K) inhibitors and that it occurred independently from Src activity, despite the observation of a strong impairment of LTD4-induced DNA synthesis following Src inhibition. More interestingly, CysLT1-R stimulation increased the production of ROS and N-acetylcysteine (NAC) abolished LTD4-induced EGF-R phosphorylation and thymidine incorporation. Collectively, our data demonstrate that in HASMC LTD4 stimulation of a Gi/o coupled CysLT1-R triggers the transactivation of the EGF-R through the intervention of PI3K and ROS. While PI3K

  12. Indirect airway challenges

    NARCIS (Netherlands)

    Joos, GF; O'Connor, B; Anderson, SD; Chung, F; Cockcroft, DW; Dahlen, B; DiMaria, G; Foresi, A; Hargreave, FE; Holgate, ST; Inman, M; Lotvall, J; Magnussen, H; Polosa, R; Postma, DS; Riedler, J

    2003-01-01

    Indirect challenges act by causing the release of endogenous mediators that cause the airway smooth muscle to contract. This is in contrast to the direct challenges where agonists such as methacholine or histamine cause airflow limitation predominantly via a direct effect on airway smooth muscle. Di

  13. Postoperative upper airway problems

    African Journals Online (AJOL)

    QuickSilver

    2003-06-09

    Jun 9, 2003 ... REVIEW ARTICLE. Southern African Journal of Anaesthesia & Analgesia - May 2003. 12. Postoperative upper airway problems way. A number of factors, some avoidable, influence the incidence ... debilitating pain, inability to swallow and temporary voice changes, and are a ..... decrease airway resistance.

  14. Pediatric airway nightmares.

    Science.gov (United States)

    D'Agostino, James

    2010-02-01

    Pediatric disorders that involve actual or potential airway compromise are among the most challenging cases that emergency department providers face. This article discusses the diagnosis and management of common and uncommon conditions in infants and children who may present with airway obstruction.

  15. Role of IRE1α/XBP-1 in Cystic Fibrosis Airway Inflammation

    Directory of Open Access Journals (Sweden)

    Carla M. P. Ribeiro

    2017-01-01

    Full Text Available Cystic fibrosis (CF pulmonary disease is characterized by chronic airway infection and inflammation. The infectious and inflamed CF airway environment impacts on the innate defense of airway epithelia and airway macrophages. The CF airway milieu induces an adaptation in these cells characterized by increased basal inflammation and a robust inflammatory response to inflammatory mediators. Recent studies have indicated that these responses depend on activation of the unfolded protein response (UPR. This review discusses the contribution of airway epithelia and airway macrophages to CF airway inflammatory responses and specifically highlights the functional importance of the UPR pathway mediated by IRE1/XBP-1 in these processes. These findings suggest that targeting the IRE1/XBP-1 UPR pathway may be a therapeutic strategy for CF airway disease.

  16. Controversies in Pediatric Perioperative Airways

    Directory of Open Access Journals (Sweden)

    Jozef Klučka

    2015-01-01

    Full Text Available Pediatric airway management is a challenge in routine anesthesia practice. Any airway-related complication due to improper procedure can have catastrophic consequences in pediatric patients. The authors reviewed the current relevant literature using the following data bases: Google Scholar, PubMed, Medline (OVID SP, and Dynamed, and the following keywords: Airway/s, Children, Pediatric, Difficult Airways, and Controversies. From a summary of the data, we identified several controversies: difficult airway prediction, difficult airway management, cuffed versus uncuffed endotracheal tubes for securing pediatric airways, rapid sequence induction (RSI, laryngeal mask versus endotracheal tube, and extubation timing. The data show that pediatric anesthesia practice in perioperative airway management is currently lacking the strong evidence-based medicine (EBM data that is available for adult subpopulations. A number of procedural steps in airway management are derived only from adult populations. However, the objective is the same irrespective of patient age: proper securing of the airway and oxygenation of the patient.

  17. Nitrites in induced sputum as a simple and cheap non-invasive marker of airway inflammation for asthmatic schoolchildren.

    Science.gov (United States)

    Recabarren, Arturo; Apaza, Carlos; Castro-Rodríguez, José A

    2008-08-01

    To determine if there are differences in the nitric oxide metabolites (nitrites) in sputum of patients with persistent asthma and healthy schoolchildren, we performed a case-control study in a tertiary care hospital in Arequipa, Perú. Nitrites in induced sputum samples were measured using the Griess assay in 30 persistent asthmatics (mean age of 10.1 yr) and 30 controls (mean age of 11.9 yr). The mean +/- s.d. of nitrites among asthmatics was significantly higher than the controls (16.30 +/- 8.6 vs. 10.25 +/- 4.68 nmol/ml, respectively, p = 0.001). Moreover, the nitrite level in the sputum in children with severe persistent asthma was higher than in the level found in the moderate and mild asthmatics (32.83 +/- 9.48 vs. 18.10 +/- 1.96 vs. 11.84 +/- 4.73 nmol/ml, respectively, p < 0.01 for linear trend). This study showed for the first time in children that asthmatics have significantly higher levels of nitrites in induced sputum than healthy controls and that the level of nitrite correlates with the severity of the asthma. Nitrite levels in sputum, a simple and cheap, non-invasive method, may be a good alternative to measure the severity of inflammation in asthmatic children.

  18. Desflurane usage during anesthesia with and without N2O using FLOW-i Automatic Gas Control with three different wash-in speeds.

    Science.gov (United States)

    De Medts, Robrecht; Carette, Rik; De Wolf, Andre M; Hendrickx, Jan F A

    2017-06-09

    AGC(®) (Automatic Gas Control) is the FLOW-i's automated low flow tool (Maquet, Solna, Sweden) that target controls the inspired O2 (FIO2) and end-expired desflurane concentration (FAdes) while (by design) exponentially decreasing fresh gas flow (FGF) during wash-in to a maintenance default FGF of 300 mL min(-1). It also offers a choice of wash-in speeds for the inhaled agents. We examined AGC performance and hypothesized that the use of lower wash-in speeds and N2O both reduce desflurane usage (Vdes). After obtaining IRB approval and patient consent, 78 ASA I-II patients undergoing abdominal surgery were randomly assigned to 1 of 6 groups (n = 13 each), depending on carrier gas (O2/air or O2/N2O) and wash-in speed (AGC speed 2, 4, or 6) of desflurane, resulting in groups air/2, air/4, air/6, N2O/2, N2O/4, and N2O/6. The target for FIO2 was set at 35%, while the FAdes target was selected so that the AGC displayed 1.3 MAC (corrected for the additive affect of N2O if used). AGC was activated upon starting mechanical ventilation. Varvel's criteria were used to describe performance of achieving the targets. Patient demographics, end-expired N2O concentration, MAC, FGF, and Vdes were compared using ANOVA. Data are presented as mean ± standard deviation, except for Varvel's criteria (median ± quartiles). Patient demographics did not differ among the groups. Median performance error was -2-0% for FIO2 and -3-1% for FAdes; median absolute performance error was 1-2% for FIO2 and 0-3% for FAdes. MAC increased faster in N2O groups, but total MAC decreased 0.1-0.25 MAC below that in the O2/air groups after 60 min. The effect of wash-in speed on Vdes faded over time. N2O decreased Vdes by 62%. AGC performance for O2 and desflurane targeting is excellent. After 1 h, the wash-in speeds tested are unlikely to affect desflurane usage. N2O usage decreases Vdes proportionally with its reduction in FAtdes.

  19. RPR 106541, a novel, airways-selective glucocorticoid: effects against antigen-induced CD4+ T lymphocyte accumulation and cytokine gene expression in the Brown Norway rat lung.

    Science.gov (United States)

    Underwood, S L; Raeburn, D; Lawrence, C; Foster, M; Webber, S; Karlsson, J A

    1997-10-01

    1. The effects of a novel 17-thiosteroid, RPR 106541, were investigated in a rat model of allergic airway inflammation. 2. In sensitized Brown Norway rats, challenge with inhaled antigen (ovalbumin) caused an influx of eosinophils and neutrophils into the lung tissue and airway lumen. In the lung tissue there was also an accumulation of CD4+ T lymphocytes and increased expression of mRNA for interleukin-4 (IL-4) and IL-5, but not interferon-gamma (IFN-gamma). These findings are consistent with an eosinophilia orchestrated by activated Th2-type cells. 3. RPR 106541 (10-300 microg kg[-1]), administered by intratracheal instillation into the airways 24 h and 1 h before antigen challenge, dose-dependently inhibited cell influx into the airway lumen. RPR 106541 (100 microg kg[-1]) caused a significant (PRPR 106541 was approximately 7 times and 4 times more potent than budesonide and fluticasone propionate, respectively. 4. When tested at a single dose (300 microg kg[-1]), RPR 106541 and fluticasone each caused a significant (PRPR 106541 and fluticasone (300 microg kg[-1]), but not budesonide (300 microg kg[-1]), significantly (PRPR 106541 (300 microg kg[-1]) also significantly (PRPR 106541 in this model, which mimics important aspects of airway inflammation in human allergic asthmatics, suggests that this glucocorticoid may be useful in the treatment of bronchial asthma.

  20. Glucocorticosteroids and beta(2)-Adrenoceptor Agonists Synergize to Inhibit Airway Smooth Muscle Remodeling

    NARCIS (Netherlands)

    Dekkers, Bart G. J.; Pehlic, Adnan; Mariani, Raissa; Bos, I. Sophie T.; Meurs, Herman; Zaagsma, Johan

    2012-01-01

    Airway remodeling, including increased airway smooth muscle (ASM) mass and contractility, contributes to increased airway narrowing in asthma. Increased ASM mass may be caused by exposure to mitogens, including platelet-derived growth factor (PDGF) and collagen type I, which induce a proliferative,

  1. Assessment of Airway Microbiota and Inflammation in Cystic Fibrosis Using Multiple Sampling Methods

    OpenAIRE

    Edith T Zemanick; Brandie D Wagner; Robertson, Charles E.; Stevens, Mark J.; Szefler, Stanley J; Accurso, Frank J.; Sagel, Scott D; Harris, J. Kirk

    2015-01-01

    Rationale: Oropharyngeal (OP) swabs and induced sputum (IS) are used for airway bacteria surveillance in nonexpectorating children with cystic fibrosis (CF). Molecular analyses of these airway samples detect complex microbial communities. However, the optimal noninvasive sampling approach for microbiota analyses and the clinical relevance of microbiota, particularly its relationship to airway inflammation, is not well characterized.

  2. Airway distensibility in Chronic Obstructive Airway Disease

    DEFF Research Database (Denmark)

    Winkler Wille, Mathilde Marie; Pedersen, Jesper Holst; Dirksen, Asger

    2013-01-01

    on the airway distensibility, defined as the ratio of relative change in lumen diameter to the relative change in total lung volume (TLV) divided by predicted total lung capacity (pTLC) . Methods – We included 1900 participants from the Danish Lung Cancer Screening Trial (DLCST); all randomized to annual low...

  3. Substrate stiffness influences TGF-β1-induced differentiation of bronchial fibroblasts into myofibroblasts in airway remodeling.

    Science.gov (United States)

    Shi, Yanling; Dong, Yuhui; Duan, Yiyuan; Jiang, Xuemei; Chen, Cheng; Deng, Linhong

    2013-02-01

    Chronic inflammation and remodeling of the bronchial wall are basic hallmarks of asthma. During the process of bronchial wall remodeling, inflammatory factors, such as transforming growth factor-β1 (TGF-β1), are known to induce the differentiation of fibroblasts into myofibroblasts, which leads to excessive synthesis and secretion of extracellular matrix (ECM) proteins, thus thickening and stiffening the basement membrane. However, it has not been thoroughly studied whether or not substrate stiffening affects the TGF-β1‑induced myofibroblast differentiation. In the present study, the influence of substrate stiffness on the process of bronchial fibroblast differentiation into myofibroblasts in the presence of TGF-β1 was investigated. To address this question, we synthesized polydimethylsiloxane (PDMS) substrates with varying degrees of stiffness (Young's modulus of 1, 10 and 50 kPa, respectively). We cultured bronchial fibroblasts on the substrates of varying stiffness in media containing TGF-β1 (10 ng/ml) to stimulate the differentiation of fibroblasts into myofibroblasts. Myofibroblast differentiation was examined using semi-quantitative RT-PCR for the expression of α-smooth muscle actin (α-SMA) mRNA and collagen I mRNA, the enzyme-linked immunosorbent assay method was used to assess the expression of collagen I protein and western blotting to assess the expression of α-SMA protein. The optical magnetic twisting cytometry (OMTC) method was used for the changing of cell mechanical properties. Our findings suggest that when fibroblasts were incubated with TGF-β1 (10 ng/ml) on substrate of varying stiffness, the differentiation of fibroblasts into myofibroblasts was enhanced by increasing substrate stiffness. Compared with those cultured on substrate with Young's modulus of 1 kPa, the mRNA and protein expression of collagen I and α-SMA of fibroblasts cultured on substrates with Young's modulus of 10 and 50 kPa were increased. Furthermore, with the

  4. 鼻咽癌放疗后困难气道1例报道%A case of radiation-induced difficult airway in a patient with nasopharyngeal carcinoma

    Institute of Scientific and Technical Information of China (English)

    Deke Li; Staying Wang; Kun Chen

    2012-01-01

    In this report, we describe radiation-induced difficult airway management in a patient with nasopharyngeal carcinoma. The patient was presented to receive laparoscopic cholecystectomy for gallbladder stone. He had been diagnosed to have nasopharyngeal cancer about 2 years ago. In operation, after sleeping, the patient was manual controlled ventilation. However, we subsequently found that his neck campaign was limited and mask ventilation was obstructed. We immediately performed oropharyngeal airway, then mask ventilation improved. Fully surface anesthesia with tetracaine atomizing to the root of tongue, larynx wall and piriform recess, the patient was endotracheal intubated with fiberoptic bronchoscope. After intubation, the patient inhaled 2.5% sevoflurane, then esmeron (50 mg) and remifentanyl (0.1 μg/kg every minute) were administrated by intravenous. After the treatment, the patient's life indexes were normal and steady. In conclusion, patients with nasopharyngeal carcinoma (NPC) after radiation therapy should be based on comprehensive evaluation of upper airway and obstructive condition before operation, then perform safe and effective tracheal intubation methods under spontaneous breathing.

  5. Small airway involvement in the late allergic response in asthma.

    Science.gov (United States)

    Stenberg, Henning; Diamant, Zuzana; Ankerst, Jaro; Bjermer, Leif; Tufvesson, Ellen

    2017-09-21

    Allergy and asthma are closely linked. Inhalation of allergen induces an early allergic response (EAR) within the airways of allergic asthmatic subjects, which is followed by a late allergic response (LAR) in approximately 50% of the subjects. The LAR is defined as a drop in forced expiratory volume in 1 s (FEV1 ) from baseline usually occurring 4-8 h after exposure, and is believed to affect small airways. However, FEV1 is insensitive to changes in small airway physiology. Our aim was to investigate and compare the pathophysiological processes in large and small airways during the EAR and the LAR, and to characterize subjects with both an EAR and a LAR (dual responders) versus those with an EAR only (single responders). Thirty-four subjects with allergic asthma underwent an inhaled allergen challenge. Lung physiology was assessed by spirometry, impulse oscillometry (IOS), body plethysmography, inert gas washout, single breath methane dilution carbon monoxide diffusion and exhaled breath temperature, at baseline and repeatedly for 23 h post-allergen challenge. Peripheral airway resistance, air trapping and ventilation heterogeneity were significantly increased in dual responders (n=15) compared to single responders (n=19) 6-8 h post-challenge. Parameters of peripheral airway resistance and ventilation heterogeneity, measured with IOS and inert gas washout, respectively, correlated at baseline and during the allergic airway response in all subjects. The LAR involves increased resistance and ventilation defects within the peripheral airways. Alternative definitions of the LAR including small airways pathophysiology could be considered. Small airway dysfunction during the LAR suggests that dual responders may have more extensive airway pathology and underscores the relevance of small airways assessment in asthma. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  6. Emergency airway puncture - slideshow

    Science.gov (United States)

    ... presentations/100113.htm Emergency airway puncture - series—Normal anatomy To ... larynx is a tubular structure in the neck, through which air passes to the lungs. The thryoid and cricoid cartilage form the narrowest ...

  7. Emergency airway puncture

    Science.gov (United States)

    ... inserted into the throat, just below the Adam's apple (cricoid cartilage), into the airway. In a hospital, ... Choking Browse the Encyclopedia A.D.A.M., Inc. is accredited by URAC, also known as the ...

  8. Inhibition of angiotensin II-induced contraction of human airway smooth muscle cells by angiotensin-(1-7) via downregulation of the RhoA/ROCK2 signaling pathway.

    Science.gov (United States)

    Li, Ning; Cai, Ruijun; Niu, Yi; Shen, Bin; Xu, Jian; Cheng, Yuanxiong

    2012-10-01

    Sustained renin-angiotensin system (RAS) activation in asthmatic patients plays a crucial role in airway hyperresponsiveness and airflow limitation. Angiotensin II (Ang II), as a key peptide of RAS, contributes to the contraction of human airway smooth muscle by activating the RhoA/Rho-associated coiled-coil containing protein kinase 2 (ROCK2) signaling pathway. Angiotensin-(1-7) [Ang-(1-7)], is a component of the angiotensin I converting enzyme 2 (ACE2)-Ang-(1-7)-Mas axis which counteracts the detrimental effects of the ACE- Ang II-angiotensin type 1 receptor (AT1R) axis in vivo; however, whether Ang-(1-7) can inhibit the effect of Ang II in the contraction of human airway smooth muscle cells (HASMCs) is unknown. In our study, collagen gel lattices and immunofluorescence were used to evaluate the contraction of HASMCs induced by Ang II. Real-time PCR and western blot analysis were performed to confirm the regulatory mechanism and the participating signaling pathway. Ang II caused the contraction of HASMCs; this effect was reversed by Ang‑(1‑7). In addition, irbesartan and A779, which are inhibitors of AT1R and Mas, respectively, attenuated the effect of Ang II and Ang-(1-7). Furthermore, Y-27632, an inhibitor of ROCK2, attenuated the Ang II-induced contraction of HASMCs by blocking the RhoA/ROCK2 signaling pathway which is involved in this contraction, and thus may be a major regulator involved in the basal maintenance of contractility in HASMCs. These data demonstrate that Ang II induces the contraction of HASMCs and that this effect can be reversed by Ang-(1-7), partially through the downregulation of of the RhoA/ROCK2 signaling pathway.

  9. Fabry disease, respiratory symptoms, and airway limitation

    DEFF Research Database (Denmark)

    Svensson, Camilla Kara; Feldt-Rasmussen, Ulla; Backer, Vibeke

    2015-01-01

    abnormalities in patients with Fabry disease. Electron microscopy of lung biopsy and induced sputum show lamellar inclusion bodies (Zebra bodies) in the cytoplasm of cells in the airway wall. X-ray and CT scan have shown patchy ground-glass pulmonary infiltrations, fibrosis, and air trapping. Fibrosis diagnosed...

  10. Airway management in trauma.

    Science.gov (United States)

    Langeron, O; Birenbaum, A; Amour, J

    2009-05-01

    Maintenance of a patent and prevention of aspiration are essential for the management of the trauma patient, that requires experienced physicians in airway control techniques. Difficulties of the airway control in the trauma setting are increased by the vital failures, the risk of aspiration, the potential cervical spine injury, the combative patient, and the obvious risk of difficult tracheal intubation related to specific injury related to the trauma. Endotracheal intubation remains the gold standard in trauma patient airway management and should be performed via the oral route with a rapid sequence induction and a manual in-line stabilization maneuver, to decrease the risks previously mentioned. Different techniques to control the airway in trauma patients are presented: improvement of the laryngoscopic vision, lighted stylet tracheal intubation, retrograde technique for orotracheal intubation, the laryngeal mask and the intubating laryngeal mask airways, the combitube and cricothyroidotomy. Management of the airway in trauma patients requires regular training in these techniques and the knowledge of complementary techniques allowing tracheal intubation or oxygenation to overcome difficult intubation and to prevent major complications as hypoxemia and aspiration.

  11. Defective activation of c-Src in cystic fibrosis airway epithelial cells results in loss of tumor necrosis factor-alpha-induced gap junction regulation

    NARCIS (Netherlands)

    Huang, Song; Dudez, Tecla; Scerri, Isabelle; Thomas, Marc A; Giepmans, Ben N G; Suter, Susanne; Chanson, Marc

    2003-01-01

    Tumor necrosis factor-alpha (TNF-alpha) signaling is central to the transmission of the innate immune response and subsequent activation of the adaptive immune system. The functioning of both systems is required for optimal clearance of pathogens from the airways. In cystic fibrosis (CF),

  12. Angiotensin II induces hypertrophy of human airway smooth muscle cells: expression of transcription factors and transforming growth factor-beta1

    NARCIS (Netherlands)

    S. McKay (Sue); J.C. de Jongste (Johan); P.R. Saxena (Pramod Ranjan); H.S. Sharma (Hari)

    1998-01-01

    textabstractIncreased smooth muscle mass due to hyperplasia and hypertrophy of airway smooth muscle (ASM) cells is a common feature in asthma. Angiotensin II (Ang II), a potent vasoconstrictor and mitogen for a wide variety of cells, has recently been implicated in bron

  13. Defective activation of c-Src in cystic fibrosis airway epithelial cells results in loss of tumor necrosis factor-alpha-induced gap junction regulation

    NARCIS (Netherlands)

    Huang, Song; Dudez, Tecla; Scerri, Isabelle; Thomas, Marc A; Giepmans, Ben N G; Suter, Susanne; Chanson, Marc

    2003-01-01

    Tumor necrosis factor-alpha (TNF-alpha) signaling is central to the transmission of the innate immune response and subsequent activation of the adaptive immune system. The functioning of both systems is required for optimal clearance of pathogens from the airways. In cystic fibrosis (CF), dysfunctio

  14. Carbon monoxide production from degradation of desflurane, enflurane, isoflurane, halothane, and sevoflurane by soda lime and Baralyme.

    Science.gov (United States)

    Fang, Z X; Eger, E I; Laster, M J; Chortkoff, B S; Kandel, L; Ionescu, P

    1995-06-01

    Anecdotal reports suggest that soda lime and Baralyme brand absorbent can degrade inhaled anesthetics to carbon monoxide (CO). We examined the factors that govern CO production and found that these include: 1) The anesthetic used: for a given minimum alveolar anesthetic concentration (MAC)-multiple, the magnitude of CO production (greatest to least) is desflurane > or = enflurane > isoflurane > halothane = sevoflurane. 2) The absorbent dryness: completely dry soda lime produces much more CO than absorbent with just 1.4% water content, and soda lime containing 4.8% or more water (standard soda lime contains 15% water) generates no CO. In contrast, both completely dry Baralyme and Baralyme with 1.6% water produce high concentrations of CO, and Baralyme containing 4.7% water produces concentrations equaling those produced by soda lime containing 1.4% water. Baralyme containing 9.7% or more water and standard Baralyme (13% water) do not generate CO.3) The type of absorbent: at a given water content, Baralyme produces more CO than does soda lime. 4) The temperature: an increased temperature increases CO production. 5) The anesthetic concentration: more CO is produced from higher anesthetic concentrations. These results suggest that CO generation can be avoided for all anesthetics by using soda lime with 4.8% (or more) water or Baralyme with 9.7% (or more) water, and by using inflow rates of less than 2-3 L/min. Such inflow rates are low enough to ensure that the absorbent does not dry out.

  15. [Blood supply to the liver in the human after 1 MAC desflurane in comparison with isoflurane and halothane].

    Science.gov (United States)

    Schindler, E; Müller, M; Zickmann, B; Kraus, H; Reuner, K H; Hempelmann, G

    1996-08-01

    Objective of this investigation was to compare the effects of the new inhalation agent desflurane with equipotent doses of isoflurane and halothane on hepatic blood flow (tHBF). 36 Patients scheduled for elective aortocoronary bypass grafting were enrolled to the study. tHBF was assessed by plasma clearance and hepatic extraction of indocyanine green, and standard haemodynamic parameters were measured by thermodilution technique. The measurements were performed awake and after intubation at equilibration of 1 MAC. All measurements were terminated before skin incision. We found a significant decrease of tHBF in all patients regardless of the inhalation agent used (H 918 ml/min +/- 107 to 625 ml/min +/- 181, I 930 ml/min +/- 195 to 637 ml/min +/- 137, D 940 ml/min +/- 129 to 677 ml/min +/- 122). The tHBF in relation to cardiac output also decreased significantly (H 17% +/- 5 to 14% +/- 3, I 16% +/- 3 to 14% +/- 5, D 20% +/- 5 to 18% +/- 6). No difference was seen between the groups according to tHBF and haemodynamics. The results of this study suggest that all inhalation agents included in the study significantly decreased tHBF during anaesthesia with the concentration of 1 MAC.

  16. Pharmacological studies of the mechanism and function of interleukin-1β-induced miRNA-146a expression in primary human airway smooth muscle

    Directory of Open Access Journals (Sweden)

    Jiang Xiaoying

    2010-06-01

    Full Text Available Abstract Background Despite the widespread induction of miR-146a during the innate immune response little is known regarding its biogenesis, function and mechanism. We have therefore examined the role of miR-146a during the interleukin (IL-1β-stimulated IL-6 and IL-8 release and proliferation in primary human airway smooth muscle (HASM cells. Methods HASM cells were isolated from human lung re-section, cultured to a maximum of 3 - 6 passages and then exposed to IL-1β. miR-146a expression were determined by qRT-PCR, IL-6 and IL-8 release by ELISA and proliferation using bromodeoxyuridine incorporation. The role of NF-κB and the MAP kinase pathways was assessed using pharmacological inhibitors of IKK2 (TPCA-1, JNK (SP600125, p38 MAP kinase (SB203580 and MEK-1/2 (PD98059. miR-146a function was determined following transfection of HASM with inhibitors and mimics using Amaxa electroporation. Results IL-1β induced a time-dependent and prolonged 100-fold induction in miR-146a expression, which correlated with release of IL-6 and IL-8. Exposure to IL-1β had no effect upon HASM proliferation. Pharmacological studies showed that expression of primary miR-146a was regulated at the transcriptional levels by NF-κB whilst post-transcriptional processing to mature miR-146a was regulated by MEK-1/2 and JNK-1/2. Functional studies indicated that IL-1β-induced miR-146a expression does not negatively regulate IL-6 and IL-8 release or basal proliferation. However, inhibition of IL-1β-induced IL-6 and IL-8 release was observed at the super-maximal intracellular miR-146a levels obtained by transfection with miR-146a mimics and indicates that studies using miRNA mimics can produce false positive results. Mechanistic studies showed that in the presence of super-maximal levels, the action of miR-146a mimics was mediated at a step following IL-6 and IL-8 mRNA transcription and not through down-regulation of IL-1 receptor associated kinase 1 (IRAK-1 and TNF

  17. Essentials of airway management, oxygenation, and ventilation: part 2: advanced airway devices: supraglottic airways.

    Science.gov (United States)

    Rosenberg, M B; Phero, J C; Becker, D E

    2014-01-01

    Offices and outpatient dental facilities must be properly equipped with devices for airway management, oxygenation, and ventilation. Part 1 in this series on emergency airway management focused on basic and fundamental considerations for supplying supplemental oxygen to the spontaneously breathing patient and utilizing a bag-valve-mask system including nasopharyngeal and oropharyngeal airways to deliver oxygen under positive pressure to the apneic patient. This article will review the evolution and use of advanced airway devices, specifically supraglottic airways, with the emphasis on the laryngeal mask airway, as the next intervention in difficult airway and ventilation management. The final part of the series (part 3) will address airway evaluation, equipment and devices for tracheal intubation, and invasive airway procedures.

  18. Effects of nitrous oxide on minimum alveolar concentration of desflurane in dogs Efeitos do óxido nitroso sobre a concentração alveolar mínima do desfluorano, em cães

    Directory of Open Access Journals (Sweden)

    C.T. Nishimori

    2007-02-01

    Full Text Available Effects of nitrous oxide (N2O on minimum alveolar concentration (MAC of desflurane were studied. For that purpose, 30 dogs were randomly allocated into two groups: desflurane group (GD and N2O and desflurane group (GDN. GD animals received propofol to intubation, and 11.5V% of desflurane diluted in 100% O2. After 30 minutes, they received electric stimulus and if the animal did not react to stimulus, desflurane concentration was reduced by 1.5V%. This protocol was repeated at each 15 minutes, and stimulus was interrupted when voluntary reaction was observed. GDN dogs were submitted to diluent flow 30% O2 and 70% N2O. Desflurane's MAC; heart (HR and respiratory (RR rates; systolic, diastolic and mean arterial pressures (SAP, DAP, and MAP, respectively; end tidal carbon dioxide (ETCO2; oxyhemoglobin saturation (SpO2 and body temperature (T were evaluated. In both groups increase in HR and ETCO2, and decrease in RR and T were associated with administration of the highest dose of desflurane. Blood pressures decreased 30 minutes after desflurane administration in GDN, and after this measurement the values increased. Reduction in desflurane's MAC was observed as well. It is concluded that N2O associated with desflurane reduced desflurane's MAC by 16% with increase in HR and respiratory depression.Estudaram-se os efeitos do óxido nitroso (N2O sobre a concentração alveolar mínima (CAM do desfluorano. Trinta cães foram distribuídos em dois grupos: desfluorano (GD e N2O e desfluorano (GDN. Os do GD receberam propofol (8,9±1,65mg/kg para intubação orotraqueal e após, 11,5V% de desfluorano em 100% de O2. Após 30 minutos, os animais receberam estímulo elétrico e não havendo reação do animal, reduziu-se a concentração em 1,5V%. Repetiu-se o protocolo a cada 15 minutos, cessando-se os estímulos quando observada reação voluntária. Os GDN foram submetidos ao mesmo protocolo, substituindo-se o fluxo diluente por 30% O2 e 70% N2O. Mensuraram

  19. Deposition of graphene nanomaterial aerosols in human upper airways.

    Science.gov (United States)

    Su, Wei-Chung; Ku, Bon Ki; Kulkarni, Pramod; Cheng, Yung Sung

    2016-01-01

    Graphene nanomaterials have attracted wide attention in recent years on their application to state-of-the-art technology due to their outstanding physical properties. On the other hand, the nanotoxicity of graphene materials also has rapidly become a serious concern especially in occupational health. Graphene naomaterials inevitably could become airborne in the workplace during manufacturing processes. The inhalation and subsequent deposition of graphene nanomaterial aerosols in the human respiratory tract could potentially result in adverse health effects to exposed workers. Therefore, investigating the deposition of graphene nanomaterial aerosols in the human airways is an indispensable component of an integral approach to graphene occupational health. For this reason, this study carried out a series of airway replica deposition experiments to obtain original experimental data for graphene aerosol airway deposition. In this study, graphene aerosols were generated, size classified, and delivered into human airway replicas (nasal and oral-to-lung airways). The deposition fraction and deposition efficiency of graphene aerosol in the airway replicas were obtained by a novel experimental approach. The experimental results acquired showed that the fractional deposition of graphene aerosols in airway sections studied were all less than 4%, and the deposition efficiency in each airway section was generally lower than 0.03. These results indicate that the majority of the graphene nanomaterial aerosols inhaled into the human respiratory tract could easily penetrate through the head airways as well as the upper part of the tracheobronchial airways and then transit down to the lower lung airways, where undesired biological responses might be induced.

  20. Airway exploration in children

    Directory of Open Access Journals (Sweden)

    Fernando GÓMEZ-SÁEZ

    2016-11-01

    Full Text Available Introduction and objective: The management of the airways represents a constant challenge in pediatric practice. In the last years, bronchoscopy has become an essential technique in the diagnosis and treatment of various abnormalities of the child's respiratory system. The special characteristics of the pediatric airway and the differentiated pathology it presents give pediatric bronchoscopy its own entity. Pediatric bronchoscopy is a safe technique with many applications, both diagnostic and therapeutic. The use of both types of bronchoscopes (flexible and rigid allows to take advantage of each one of them. Flexible bronchoscopy in pediatrics is a relatively simple and low-risk procedure that provides anatomical and dynamic information on the airways, as well as cytological and microbiological studies. The simplicity and low risk of this technique, in addition to not requiring general anesthesia, allows it to be performed even at the head of the patient, which has led to an increasingly extensive field of indications. The purpose of this article is to provide a review on the timeliness of the pediatric bronchoscopy procedure, especially about its indications. Method: Narrative review. Conclusion: The endoscopic examination of the airway is a cost-effective technique in pediatrics, with little complications and can offer very valuable diagnostic information, as well as perform certain therapeutic procedures. It is recommended that all professionals involved in the management of patients with airway pathology should know their indications, contraindications, complications, as well as their therapeutic applications.

  1. Integrated care pathways for airway diseases (AIRWAYS-ICPs)

    NARCIS (Netherlands)

    Bousquet, J.; Addis, A.; Adcock, I.; Agache, I.; Agusti, A.; Alonso, A.; Annesi-Maesano, I.; Anto, J. M.; Bachert, C.; Baena-Cagnani, C. E.; Bai, C.; Baigenzhin, A.; Barbara, C.; Barnes, P. J.; Bateman, E. D.; Beck, L.; Bedbrook, A.; Bel, E. H.; Benezet, O.; Bennoor, K. S.; Benson, M.; Bernabeu-Wittel, M.; Bewick, M.; Bindslev-Jensen, C.; Blain, H.; Blasi, F.; Bonini, M.; Bonini, S.; Boulet, L. P.; Bourdin, A.; Bourret, R.; Bousquet, P. J.; Brightling, C. E.; Briggs, A.; Brozek, J.; Buh, R.; Bush, A.; Caimmi, D.; Calderon, M.; Calverley, P.; Camargos, P. A.; Camuzat, T.; Canonica, G. W.; Carlsen, K. H.; Casale, T. B.; Cazzola, M.; Sarabia, A. M. Cepeda; Cesario, A.; Chen, Y. Z.; Chkhartishvili, E.; Chavannes, N. H.; Chiron, R.; Chuchalin, A.; Chung, K. F.; Cox, L.; Crooks, G.; Crooks, M. G.; Cruz, A. A.; Custovic, A.; Dahl, R.; Dahlen, S. E.; De Blay, F.; Dedeu, T.; Deleanu, D.; Demoly, P.; Devillier, P.; Didier, A.; Dinh-Xuan, A. T.; Djukanovic, R.; Dokic, D.; Douagui, H.; Dubakiene, R.; Eglin, S.; Elliot, F.; Emuzyte, R.; Fabbri, L.; Wagner, A. Fink; Fletcher, M.; Fokkens, W. J.; Fonseca, J.; Franco, A.; Frith, P.; Furber, A.; Gaga, M.; Garces, J.; Garcia-Aymerich, J.; Gamkrelidze, A.; Gonzales-Diaz, S.; Gouzi, F.; Guzman, M. A.; Haahtela, T.; Harrison, D.; Hayot, M.; Heaney, L. G.; Heinrich, J.; Hellings, P. W.; Hooper, J.; Humbert, M.; Hyland, M.; Iaccarino, G.; Jakovenko, D.; Jardim, J. R.; Jeandel, C.; Jenkins, C.; Johnston, S. L.; Jonquet, O.; Joos, G.; Jung, K. S.; Kalayci, O.; Karunanithi, S.; Keil, T.; Khaltaev, N.; Kolek, V.; Kowalski, M. L.; Kull, I.; Kuna, P.; Kvedariene, V.; Le, L. T.; Carlsen, K. C. Lodrup; Louis, R.; MacNee, W.; Mair, A.; Majer, I.; Manning, P.; Keenoy, E. de Manuel; Masjedi, M. R.; Meten, E.; Melo-Gomes, E.; Menzies-Gow, A.; Mercier, G.; Mercier, J.; Michel, J. P.; Miculinic, N.; Mihaltan, F.; Milenkovic, B.; Molimard, M.; Mamas, I.; Montilla-Santana, A.; Morais-Almeida, M.; Morgan, M.; N'Diaye, M.; Nafti, S.; Nekam, K.; Neou, A.; Nicod, L.; O'Hehir, R.; Ohta, K.; Paggiaro, P.; Palkonen, S.; Palmer, S.; Papadopoulos, N. G.; Papi, A.; Passalacqua, G.; Pavord, I.; Pigearias, B.; Plavec, D.; Postma, D. S.; Price, D.; Rabe, K. F.; Pontal, F. Radier; Redon, J.; Rennard, S.; Roberts, J.; Robine, J. M.; Roca, J.; Roche, N.; Rodenas, F.; Roggeri, A.; Rolland, C.; Rosado-Pinto, J.; Ryan, D.; Samolinski, B.; Sanchez-Borges, M.; Schunemann, H. J.; Sheikh, A.; Shields, M.; Siafakas, N.; Sibille, Y.; Similowski, T.; Small, I.; Sola-Morales, O.; Sooronbaev, T.; Stelmach, R.; Sterk, P. J.; Stiris, T.; Sud, P.; Tellier, V.; To, T.; Todo-Bom, A.; Triggiani, M.; Valenta, R.; Valero, A. L.; Valiulis, A.; Valovirta, E.; Van Ganse, E.; Vandenplas, O.; Vasankari, T.; Vestbo, J.; Vezzani, G.; Viegi, G.; Visier, L.; Vogelmeier, C.; Vontetsianos, T.; Wagstaff, R.; Wahn, U.; Wallaert, B.; Whalley, B.; Wickman, M.; Williams, D. M.; Wilson, N.; Yawn, B. P.; Yiallouros, P. K.; Yorgancioglu, A.; Yusuf, O. M.; Zar, H. J.; Zhong, N.; Zidarn, M.; Zuberbier, T.

    2014-01-01

    The objective of Integrated Care Pathways for Airway Diseases (AIRWAYS-ICPs) is to launch a collaboration to develop multi-sectoral care pathways for chronic respiratory diseases in European countries and regions. AIRWAYS-ICPs has strategic relevance to the European Union Health Strategy and will ad

  2. Integrated care pathways for airway diseases (AIRWAYS-ICPs)

    NARCIS (Netherlands)

    Bousquet, J.; Addis, A.; Adcock, I.; Agache, I.; Agusti, A.; Alonso, A.; Annesi-Maesano, I.; Anto, J. M.; Bachert, C.; Baena-Cagnani, C. E.; Bai, C.; Baigenzhin, A.; Barbara, C.; Barnes, P. J.; Bateman, E. D.; Beck, L.; Bedbrook, A.; Bel, E. H.; Benezet, O.; Bennoor, K. S.; Benson, M.; Bernabeu-Wittel, M.; Bewick, M.; Bindslev-Jensen, C.; Blain, H.; Blasi, F.; Bonini, M.; Bonini, S.; Boulet, L. P.; Bourdin, A.; Bourret, R.; Bousquet, P. J.; Brightling, C. E.; Briggs, A.; Brozek, J.; Buh, R.; Bush, A.; Caimmi, D.; Calderon, M.; Calverley, P.; Camargos, P. A.; Camuzat, T.; Canonica, G. W.; Carlsen, K. H.; Casale, T. B.; Cazzola, M.; Sarabia, A. M. Cepeda; Cesario, A.; Chen, Y. Z.; Chkhartishvili, E.; Chavannes, N. H.; Chiron, R.; Chuchalin, A.; Chung, K. F.; Cox, L.; Crooks, G.; Crooks, M. G.; Cruz, A. A.; Custovic, A.; Dahl, R.; Dahlen, S. E.; De Blay, F.; Dedeu, T.; Deleanu, D.; Demoly, P.; Devillier, P.; Didier, A.; Dinh-Xuan, A. T.; Djukanovic, R.; Dokic, D.; Douagui, H.; Dubakiene, R.; Eglin, S.; Elliot, F.; Emuzyte, R.; Fabbri, L.; Wagner, A. Fink; Fletcher, M.; Fokkens, W. J.; Fonseca, J.; Franco, A.; Frith, P.; Furber, A.; Gaga, M.; Garces, J.; Garcia-Aymerich, J.; Gamkrelidze, A.; Gonzales-Diaz, S.; Gouzi, F.; Guzman, M. A.; Haahtela, T.; Harrison, D.; Hayot, M.; Heaney, L. G.; Heinrich, J.; Hellings, P. W.; Hooper, J.; Humbert, M.; Hyland, M.; Iaccarino, G.; Jakovenko, D.; Jardim, J. R.; Jeandel, C.; Jenkins, C.; Johnston, S. L.; Jonquet, O.; Joos, G.; Jung, K. S.; Kalayci, O.; Karunanithi, S.; Keil, T.; Khaltaev, N.; Kolek, V.; Kowalski, M. L.; Kull, I.; Kuna, P.; Kvedariene, V.; Le, L. T.; Carlsen, K. C. Lodrup; Louis, R.; MacNee, W.; Mair, A.; Majer, I.; Manning, P.; Keenoy, E. de Manuel; Masjedi, M. R.; Meten, E.; Melo-Gomes, E.; Menzies-Gow, A.; Mercier, G.; Mercier, J.; Michel, J. P.; Miculinic, N.; Mihaltan, F.; Milenkovic, B.; Molimard, M.; Mamas, I.; Montilla-Santana, A.; Morais-Almeida, M.; Morgan, M.; N'Diaye, M.; Nafti, S.; Nekam, K.; Neou, A.; Nicod, L.; O'Hehir, R.; Ohta, K.; Paggiaro, P.; Palkonen, S.; Palmer, S.; Papadopoulos, N. G.; Papi, A.; Passalacqua, G.; Pavord, I.; Pigearias, B.; Plavec, D.; Postma, D. S.; Price, D.; Rabe, K. F.; Pontal, F. Radier; Redon, J.; Rennard, S.; Roberts, J.; Robine, J. M.; Roca, J.; Roche, N.; Rodenas, F.; Roggeri, A.; Rolland, C.; Rosado-Pinto, J.; Ryan, D.; Samolinski, B.; Sanchez-Borges, M.; Schunemann, H. J.; Sheikh, A.; Shields, M.; Siafakas, N.; Sibille, Y.; Similowski, T.; Small, I.; Sola-Morales, O.; Sooronbaev, T.; Stelmach, R.; Sterk, P. J.; Stiris, T.; Sud, P.; Tellier, V.; To, T.; Todo-Bom, A.; Triggiani, M.; Valenta, R.; Valero, A. L.; Valiulis, A.; Valovirta, E.; Van Ganse, E.; Vandenplas, O.; Vasankari, T.; Vestbo, J.; Vezzani, G.; Viegi, G.; Visier, L.; Vogelmeier, C.; Vontetsianos, T.; Wagstaff, R.; Wahn, U.; Wallaert, B.; Whalley, B.; Wickman, M.; Williams, D. M.; Wilson, N.; Yawn, B. P.; Yiallouros, P. K.; Yorgancioglu, A.; Yusuf, O. M.; Zar, H. J.; Zhong, N.; Zidarn, M.; Zuberbier, T.

    The objective of Integrated Care Pathways for Airway Diseases (AIRWAYS-ICPs) is to launch a collaboration to develop multi-sectoral care pathways for chronic respiratory diseases in European countries and regions. AIRWAYS-ICPs has strategic relevance to the European Union Health Strategy and will

  3. Virus- and interferon-induced loss of inhibitory M2 muscarinic receptor function and gene expression in cultured airway parasympathetic neurons.

    OpenAIRE

    Jacoby, D B; Xiao, H Q; Lee, N. H.; Chan-Li, Y; Fryer, A. D.

    1998-01-01

    Viral infections increase vagally mediated reflex bronchoconstriction. Decreased function of inhibitory M2 muscarinic receptors on the parasympathetic nerve endings is likely to contribute to increased acetylcholine release. In this study, we used cultured airway parasympathetic neurons to determine the effects of parainfluenza virus and of interferon (IFN)-gamma on acetylcholine release, inhibitory M2 receptor function, and M2 receptor gene expression. In control cultures, electrically stimu...

  4. Numerical analysis of respiratory flow patterns within human upper airway

    Science.gov (United States)

    Wang, Ying; Liu, Yingxi; Sun, Xiuzhen; Yu, Shen; Gao, Fei

    2009-12-01

    A computational fluid dynamics (CFD) approach is used to study the respiratory airflow dynamics within a human upper airway. The airway model which consists of the airway from nasal cavity, pharynx, larynx and trachea to triple bifurcation is built based on the CT images of a healthy volunteer and the Weibel model. The flow characteristics of the whole upper airway are quantitatively described at any time level of respiratory cycle. Simulation results of respiratory flow show good agreement with the clinical measures, experimental and computational results in the literature. The air mainly passes through the floor of the nasal cavity in the common, middle and inferior nasal meatus. The higher airway resistance and wall shear stresses are distributed on the posterior nasal valve. Although the airways of pharynx, larynx and bronchi experience low shear stresses, it is notable that relatively high shear stresses are distributed on the wall of epiglottis and bronchial bifurcations. Besides, two-dimensional fluid-structure interaction models of normal and abnormal airways are built to discuss the flow-induced deformation in various anatomy models. The result shows that the wall deformation in normal airway is relatively small.

  5. Airway reconstruction in children

    Directory of Open Access Journals (Sweden)

    Rao Sanjay

    2009-01-01

    Full Text Available Aim/Background : Airway anomalies are infrequent but potentially life threatening in children. A program to care for these difficult children was set up at our institution, and this paper summarizes our experience. Methods: A total of 34 children were enrolled in the program over a period of three years. These children were evaluated as per the standard protocols. Treatment was individualized. Results: Of these 34 children, 28 had their airways restored and are doing well. Four children continue to remain on tracheostomy and two will require long term tracheostomy. There were two deaths. All children are under surveillance as there is a risk of recurrence. Conclusions: Airway anomalies are complex problems with significant morbidity and mortality. Current therapeutic modalities allow for good results. Most children were successfully decannulated and did well.

  6. Paediatric airway management: basic aspects

    DEFF Research Database (Denmark)

    Holm-Knudsen, R J; Rasmussen, L S

    2009-01-01

    . Airway obstruction can be avoided by paying close attention to the positioning of the head of the child and by keeping the mouth of the child open during mask ventilation. The use of oral and nasopharyngeal airways, laryngeal mask airways, and cuffed endotracheal tubes is discussed with special reference...... to the circumstances in infants. A slightly different technique during laryngoscopy is suggested. The treatment of airway oedema and laryngospasm is described....

  7. TGF-β-activated kinase 1 (TAK1 signaling regulates TGF-β-induced WNT-5A expression in airway smooth muscle cells via Sp1 and β-catenin.

    Directory of Open Access Journals (Sweden)

    Kuldeep Kumawat

    Full Text Available WNT-5A, a key player in embryonic development and post-natal homeostasis, has been associated with a myriad of pathological conditions including malignant, fibroproliferative and inflammatory disorders. Previously, we have identified WNT-5A as a transcriptional target of TGF-β in airway smooth muscle cells and demonstrated its function as a mediator of airway remodeling. Here, we investigated the molecular mechanisms underlying TGF-β-induced WNT-5A expression. We show that TGF-β-activated kinase 1 (TAK1 is a critical mediator of WNT-5A expression as its pharmacological inhibition or siRNA-mediated silencing reduced TGF-β induction of WNT-5A. Furthermore, we show that TAK1 engages p38 and c-Jun N-terminal kinase (JNK signaling which redundantly participates in WNT-5A induction as only simultaneous, but not individual, inhibition of p38 and JNK suppressed TGF-β-induced WNT-5A expression. Remarkably, we demonstrate a central role of β-catenin in TGF-β-induced WNT-5A expression. Regulated by TAK1, β-catenin is required for WNT-5A induction as its silencing repressed WNT-5A expression whereas a constitutively active mutant augmented basal WNT-5A abundance. Furthermore, we identify Sp1 as the transcription factor for WNT-5A and demonstrate its interaction with β-catenin. We discover that Sp1 is recruited to the WNT-5A promoter in a TGF-β-induced and TAK1-regulated manner. Collectively, our findings describe a TAK1-dependent, β-catenin- and Sp1-mediated signaling cascade activated downstream of TGF-β which regulates WNT-5A induction.

  8. 过氧亚硝基阴离子对气道上皮细胞的损伤作用%Airway epithelial injury induced by peroxynitrite

    Institute of Scientific and Technical Information of China (English)

    朱铁年; 赵瑞景; 凌亦凌; 谷振勇; 周君琳

    2001-01-01

    目的:探讨过氧亚硝基阴离子(ONOO-)对气道上皮细胞的损伤作用。方法:在培养的大鼠气道上皮(RTE)细胞观察外源性给予ONOO-对RTE细胞线粒体呼吸、8-羟基脱氧鸟苷(8-OHdG)水平、乳酸脱氢酶(LDH)释放及凋亡细胞百分率的影响。结果:ONOO-(0.25-1 mmol/L)呈剂量依赖方式抑制RTE细胞线粒体呼吸功能、增高LDH释放率。并呈剂量依赖性引起8-OHdG水平升高。不同浓度(0.25 mmol/L、0.5 mmol/L及1 mmol/L)ONOO-均以时间依赖方式引起RTE细胞凋亡。结论:ONOO-可引起培养的RTE细胞发生凋亡和坏死。低浓度的ONOO- 损伤RTE细胞以凋亡为主;高浓度的ONOO-可能主要引起RTE细胞发生坏死。ONOO-对RTE细胞线粒体呼吸抑制和DNA的氧化损伤可能是ONOO-导致RTE细胞坏死和凋亡的主要原因。%AIM:To study the effect of ONOO- on the airway epithelial injury. METHODS: The mitochondrial respiration, the amount of lactate dedydrogenase (LDH) release into the cell culture medium, the levels of 8-hydroxy-2′-deoxyguanosine (8-OHdG), and the cellular apoptosis were examined after exposure of cultured rat tracheal epithelial (RTE) cells to ONOO-. RESULTS: Exposure of RTE cells to 0.25, 0.5 and 1 mmol/L ONOO- caused a dose-dependent suppression of the mitochondrial respiration . ONOO- also caused a dose-dependent increase in the percentage of LDH release. Exposure of RTE cells to ONOO- resulted in an increased generation of 8-OHdG in a dose-dependent manner. ONOO- caused an increase in apoptotic percentage in RTE cells in a time-dependent manner at different concentrations. CONCLUSION: ONOO- could cause necrosis and apoptosis in cultured RTE cells. Low concentration of ONOO- caused apoptosis in a time-dependent manner. Whereas exposure to high concentration of ONOO- resulted in cell necrosis, ONOO- caused a dose-dependent increase in the percentage of LDH release. Suppression of mitochondrial respiration

  9. L-ornithine derived polyamines in cystic fibrosis airways.

    Directory of Open Access Journals (Sweden)

    Hartmut Grasemann

    Full Text Available Increased arginase activity contributes to airway nitric oxide (NO deficiency in cystic fibrosis (CF. Whether down-stream products of arginase activity contribute to CF lung disease is currently unknown. The objective of this study was to test whether L-ornithine derived polyamines are present in CF airways and contribute to airway pathophysiology. Polyamine concentrations were measured in sputum of patients with CF and in healthy controls, using liquid chromatography-tandem mass spectrometry. The effect of spermine on airway smooth muscle mechanical properties was assessed in bronchial segments of murine airways, using a wire myograph. Sputum polyamine concentrations in stable CF patients were similar to healthy controls for putrescine and spermidine but significantly higher for spermine. Pulmonary exacerbations were associated with an increase in sputum and spermine levels. Treatment for pulmonary exacerbations resulted in decreases in arginase activity, L-ornithine and spermine concentrations in sputum. The changes in sputum spermine with treatment correlated significantly with changes in L-ornithine but not with sputum inflammatory markers. Incubation of mouse bronchi with spermine resulted in an increase in acetylcholine-induced force and significantly reduced nitric oxide-induced bronchial relaxation. The polyamine spermine is increased in CF airways. Spermine contributes to airways obstruction by reducing the NO-mediated smooth muscle relaxation.

  10. Distinct PKA and Epac compartmentalization in airway function and plasticity

    NARCIS (Netherlands)

    Dekkers, Bart G. J.; Racke, Kurt; Schmidt, Martina

    2013-01-01

    Asthma and chronic obstructive pulmonary disease (COPD) are obstructive lung diseases characterized by airway obstruction, airway inflammation and airway remodelling. Next to inflammatory cells and airway epithelial cells, airway mesenchymal cells, including airway smooth muscle cells and (myo)fibro

  11. Desflurane consumption during automated closed-circuit delivery is higher than when a conventional anesthesia machine is used with a simple vaporizer-O2-N2O fresh gas flow sequence

    Directory of Open Access Journals (Sweden)

    Sosnowski Maurice

    2008-07-01

    Full Text Available Abstract Background The Zeus® (Dräger, Lübeck, Germany, an automated closed-circuit anesthesia machine, uses high fresh gas flows (FGF to wash-in the circuit and the lungs, and intermittently flushes the system to remove unwanted N2. We hypothesized this could increase desflurane consumption to such an extent that agent consumption might become higher than with a conventional anesthesia machine (Anesthesia Delivery Unit [ADU®], GE, Helsinki, Finland used with a previously derived desflurane-O2-N2O administration schedule that allows early FGF reduction. Methods Thirty-four ASA PS I or II patients undergoing plastic, urologic, or gynecologic surgery received desflurane in O2/N2O. In the ADU group (n = 24, an initial 3 min high FGF of O2 and N2O (2 and 4 L.min-1, respectively was used, followed by 0.3 L.min-1 O2 + 0.4 L.min-1 N2O. The desflurane vaporizer setting (FD was 6.5% for the first 15 min, and 5.5% during the next 25 min. In the Zeus group (n = 10, the Zeus® was used in automated closed circuit anesthesia mode with a selected end-expired (FA desflurane target of 4.6%, and O2/N2O as the carrier gases with a target inspired O2% of 30%. Desflurane FA and consumption during the first 40 min were compared using repeated measures one-way ANOVA. Results Age and weight did not differ between the groups (P > 0.05, but patients in the Zeus group were taller (P = 0.04. In the Zeus group, the desflurane FA was lower during the first 3 min (P 0.05, and slightly higher after 4 min (P A between the two groups. Conclusion Agent consumption with an automated closed-circuit anesthesia machine is higher than with a conventional anesthesia machine when the latter is used with a specific vaporizer-FGF sequence. Agent consumption during automated delivery might be further reduced by optimizing the algorithm(s that manages the initial FGF or by tolerating some N2 in the circuit to minimize the need for intermittent flushing.

  12. Airway Responsiveness to Psychological Processes in Asthma and Health

    Directory of Open Access Journals (Sweden)

    Thomas eRitz

    2012-09-01

    Full Text Available Psychosocial factors have been found to impact airway pathophysiology in respiratory disease with considerable consistency. Influences on airway mechanics have been studied particularly well. The goal of this article is to review the literature on airway responses to psychological stimulation, discuss potential pathways of influence, and present a well-established emotion-induction paradigm to study airway obstruction elicited by unpleasant stimuli. Observational studies have found systematic associations between lung function and daily mood changes. The laboratory –based paradigm of bronchoconstrictive suggestion has been used successfully to elicit airway obstruction in a substantial proportion of asthmatic individuals. Other studies have demonstrated an enhancement of airway responses to standard airway challenges with exercise, allergens, or methacholine. Standardized emotion-induction techniques have consistently shown airway constriction during unpleasant stimulation, with surgery, blood and injury stimuli being particularly powerful. Findings with various forms of stress induction have been more mixed. A number of methodological factors may account for variability across studies, such as choice of measurement technique, temporal association between stimulation and measurement, and the specific quality and intensity of the stimulus material, in particular the extent of implied action-orientation. Research has also begun to elucidate physiological processes associated with psychologically induced airway responses, with vagal excitation and ventilatory influences being the most likely candidate pathways, whereas the role of specific central nervous system pathways and inflammatory processes has been less studied. The technique of emotion-induction using films has the potential to become a standardized challenge paradigm for the further exploration of airway hyperresponsiveness mediated by central nervous system processes.

  13. IFNβ/TNFα synergism induces a non-canonical STAT2/IRF9-dependent pathway triggering a novel DUOX2 NADPH Oxidase-mediated airway antiviral response

    Institute of Scientific and Technical Information of China (English)

    Karin Fink; Lydie Martin; Esperance Mukawera; Stéfany Chartier; Xavier De Deken; Emmanuelle Brochiero; Fran(c)oise Miot

    2013-01-01

    Airway epithelial cells are key initial innate immune responders in the fight against respiratory viruses,primarily via the secretion of antiviral and proinflammatory cytokines that act in an autocrine/paracrine fashion to trigger the establishment of an antiviral state.It is currently thought that the early antiviral state in airway epithelial cells primarily relies on IFNβ secretion and the subsequent activation of the interferon-stimulated gene factor 3 (ISGF3) transcription factor complex,composed of STAT1,STAT2 and IRF9,which regulates the expression of a panoply of interferon-stimulated genes encoding proteins with antiviral activities.However,the specific pathways engaged by the synergistic action of different cytokines during viral infections,and the resulting physiological outcomes are still ill-defined.Here,we unveil a novel delayed antiviral response in the airways,which is initiated by the synergistic autocrine/paracrine action of IFNβ and TNFα,and signals through a non-canonical STAT2-and IRF9-dependent,but STAT1-independent cascade.This pathway ultimately leads to the late induction of the DUOX2 NADPH oxidase expression.Importantly,our study uncovers that the development of the antiviral state relies on DUOX2-dependent H2O2 production.Key antiviral pathways are often targeted by evasion strategies evolved by various pathogenic viruses.In this regard,the importance of the novel DUOX2-dependent antiviral pathway is further underlined by the observation that the human respiratory syncytial virus is able to subvert DUOX2 induction.

  14. Advances in prehospital airway management.

    Science.gov (United States)

    Jacobs, Pe; Grabinsky, A

    2014-01-01

    Prehospital airway management is a key component of emergency responders and remains an important task of Emergency Medical Service (EMS) systems worldwide. The most advanced airway management techniques involving placement of oropharyngeal airways such as the Laryngeal Mask Airway or endotracheal tube. Endotracheal tube placement success is a common measure of out-of-hospital airway management quality. Regional variation in regard to training, education, and procedural exposure may be the major contributor to the findings in success and patient outcome. In studies demonstrating poor outcomes related to prehospital-attempted endotracheal intubation (ETI), both training and skill level of the provider are usually often low. Research supports a relationship between the number of intubation experiences and ETI success. National standards for certification of emergency medicine provider are in general too low to guarantee good success rate in emergency airway management by paramedics and physicians. Some paramedic training programs require more intense airway training above the national standard and some EMS systems in Europe staff their system with anesthesia providers instead. ETI remains the cornerstone of definitive prehospital airway management, However, ETI is not without risk and outcomes data remains controversial. Many systems may benefit from more input and guidance by the anesthesia department, which have higher volumes of airway management procedures and extensive training and experience not just with training of airway management but also with different airway management techniques and adjuncts.

  15. Extraglottic airway devices: technology update

    Directory of Open Access Journals (Sweden)

    Sharma B

    2017-08-01

    Full Text Available Bimla Sharma, Chand Sahai, Jayashree Sood Department of Anaesthesiology, Pain and Perioperative Medicine, Sir Ganga Ram Hospital, New Delhi, India Abstract: Extraglottic airway devices (EADs have revolutionized the field of airway management. The invention of the laryngeal mask airway was a game changer, and since then, there have been several innovations to improve the EADs in design, functionality, safety and construction material. These have ranged from changes in the shape of the mask, number of cuffs and material used, like rubber, polyvinylchloride and latex. Phthalates, which were added to the construction material in order to increase device flexibility, were later omitted when this chemical was found to have serious adverse reproductive outcomes. The various designs brought out by numerous companies manufacturing EADs resulted in the addition of several devices to the airway market. These airway devices were put to use, many of them with inadequate or no evidence base regarding their efficacy and safety. To reduce the possibility of compromising the safety of the patient, the Difficult Airway Society (DAS formed the Airway Device Evaluation Project Team (ADEPT to strengthen the evidence base for airway equipment and vet the new extraglottic devices. A preuse careful analysis of the design and structure may help in better understanding of the functionality of a particular device. In the meantime, the search for the ideal EAD continues. Keywords: extraglottic airway devices, laryngeal mask airway, other extraglottic airway devices, safety, technology update

  16. Supraglottic airway devices in children

    Directory of Open Access Journals (Sweden)

    S Ramesh

    2011-01-01

    Full Text Available Modern anaesthesia practice in children was made possible by the invention of the endotracheal tube (ET, which made lengthy and complex surgical procedures feasible without the disastrous complications of airway obstruction, aspiration of gastric contents or asphyxia. For decades, endotracheal intubation or bag-and-mask ventilation were the mainstays of airway management. In 1983, this changed with the invention of the laryngeal mask airway (LMA, the first supraglottic airway device that blended features of the facemask with those of the ET, providing ease of placement and hands-free maintenance along with a relatively secure airway. The invention and development of the LMA by Dr. Archie Brain has had a significant impact on the practice of anaesthesia, management of the difficult airway and cardiopulmonary resuscitation in children and neonates. This review article will be a brief about the clinical applications of supraglottic airways in children.

  17. Astragalin inhibits autophagy-associated airway epithelial fibrosis

    OpenAIRE

    Cho, In-Hee; Choi, Yean-Jung; Gong, Ju-Hyun; Shin, Daekeun; Kang, Min-Kyung; Kang, Young-Hee

    2015-01-01

    Background Fibrotic remodeling of airway and lung parenchymal compartments is attributed to pulmonary dysfunction with an involvement of reactive oxygen species (ROS) in chronic lung diseases such as idiopathic pulmonary fibrosis and asthma. Methods The in vitro study elucidated inhibitory effects of astragalin, kaempferol-3-O-glucoside from leaves of persimmon and green tea seeds, on oxidative stress-induced airway fibrosis. The in vivo study explored the demoting effects of astragalin on ep...

  18. Airway epithelial cell responses to ozone injury

    Energy Technology Data Exchange (ETDEWEB)

    Leikauf, G.D.; Simpson, L.G.; Zhao, Qiyu [Univ. of Cincinnati Medical Center, OH (United States)] [and others

    1995-03-01

    The airway epithelial cell is an important target in ozone injury. Once activated, the airway epithelium responds in three phases. The initial, or immediate phase, involves activation of constitutive cells, often through direct covalent interactions including the formation of secondary ozonolysis products-hydroxyhydroperoxides, aldehydes, and hydrogen peroxide. Recently, we found hydroxyhydroperoxides to be potent agonists; of bioactive eicosanoid formation by human airway epithelial cells in culture. Other probable immediate events include activation and inactivation of enzymes present on the epithelial surface (e.g., neutral endopeptidase). During the next 2 to 24 hr, or early phase, epithelial cells respond by synthesis and release of chemotactic factors, including chemokines-macrophage inflammatory protein-2, RANTES, and interleukin-8. Infiltrating leukocytes during this period also release elastase, an important agonist of epithelial cell mucus secretion and additional chemokine formation. The third (late) phase of ozone injury