The Experts below are selected from a list of 54948 Experts worldwide ranked by ideXlab platform
Philippe Devillier - One of the best experts on this subject based on the ideXlab platform.
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the long acting β2 adrenoceptor agonist olodaterol attenuates Pulmonary Inflammation
British Journal of Pharmacology, 2015Co-Authors: Ines Kollak, Matthias J Duechs, Emmanuel Naline, Lutz Wollin, Philippe DevillierAbstract:Background and Purpose β2-adrenoceptor agonists are widely used in the management of obstructive airway diseases. Besides their bronchodilatory effect, several studies suggest inhibitory effects on various aspects of Inflammation. The aim of our study was to determine the efficacy of the long-acting β2-adrenoceptor agonist olodaterol to inhibit Pulmonary Inflammation and to elucidate mechanism(s) underlying its anti-inflammatory actions. Experimental Approach Olodaterol was tested in murine and guinea pig models of cigarette smoke- and LPS-induced lung Inflammation. Furthermore, effects of olodaterol on the LPS-induced pro-inflammatory mediator release from human parenchymal explants, CD11b adhesion molecule expression on human granulocytes TNF-α release from human whole blood and on the IL-8-induced migration of human peripheral blood neutrophils were investigated. Key Results Olodaterol dose-dependently attenuated cell influx and pro-inflammatory mediator release in murine and guinea pig models of Pulmonary Inflammation. These anti-inflammatory effects were observed at doses relevant to their bronchodilatory efficacy. Mechanistically, olodaterol attenuated pro-inflammatory mediator release from human parenchymal explants and whole blood and reduced expression of CD11b adhesion molecules on granulocytes, but without direct effects on IL-8-induced neutrophil transwell migration. Conclusions and Implications This is the first evidence for the anti-inflammatory efficacy of a β2-adrenoceptor agonist in models of lung Inflammation induced by cigarette smoke. The long-acting β2-adrenoceptor agonist olodaterol attenuated Pulmonary Inflammation through mechanisms that are separate from direct inhibition of bronchoconstriction. Furthermore, the in vivo data suggest that the anti-inflammatory properties of olodaterol are maintained after repeated dosing for 4 days.
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The long‐acting β2‐adrenoceptor agonist olodaterol attenuates Pulmonary Inflammation
British Journal of Pharmacology, 2015Co-Authors: Ines Kollak, Matthias J Duechs, Emmanuel Naline, Lutz Wollin, Philippe DevillierAbstract:Background and Purpose β2-adrenoceptor agonists are widely used in the management of obstructive airway diseases. Besides their bronchodilatory effect, several studies suggest inhibitory effects on various aspects of Inflammation. The aim of our study was to determine the efficacy of the long-acting β2-adrenoceptor agonist olodaterol to inhibit Pulmonary Inflammation and to elucidate mechanism(s) underlying its anti-inflammatory actions. Experimental Approach Olodaterol was tested in murine and guinea pig models of cigarette smoke- and LPS-induced lung Inflammation. Furthermore, effects of olodaterol on the LPS-induced pro-inflammatory mediator release from human parenchymal explants, CD11b adhesion molecule expression on human granulocytes TNF-α release from human whole blood and on the IL-8-induced migration of human peripheral blood neutrophils were investigated. Key Results Olodaterol dose-dependently attenuated cell influx and pro-inflammatory mediator release in murine and guinea pig models of Pulmonary Inflammation. These anti-inflammatory effects were observed at doses relevant to their bronchodilatory efficacy. Mechanistically, olodaterol attenuated pro-inflammatory mediator release from human parenchymal explants and whole blood and reduced expression of CD11b adhesion molecules on granulocytes, but without direct effects on IL-8-induced neutrophil transwell migration. Conclusions and Implications This is the first evidence for the anti-inflammatory efficacy of a β2-adrenoceptor agonist in models of lung Inflammation induced by cigarette smoke. The long-acting β2-adrenoceptor agonist olodaterol attenuated Pulmonary Inflammation through mechanisms that are separate from direct inhibition of bronchoconstriction. Furthermore, the in vivo data suggest that the anti-inflammatory properties of olodaterol are maintained after repeated dosing for 4 days.
Masaru Sagai - One of the best experts on this subject based on the ideXlab platform.
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Ebselen decreases ozone-induced Pulmonary Inflammation in rats.
Lung, 2000Co-Authors: Yukio Ishii, Ken-ichi Hashimoto, Kuniyoshi Hirano, Yuko Morishima, Mie Mochizuki, Kuniko Masuyama, Akihiro Nomura, Tohru Sakamoto, Yoshiyuki Uchida, Masaru SagaiAbstract:We studied the effects of ebselen on rat lung inflammatory responses against ozone exposure. Rats were treated with ebselen every 12 h from 1 h before a single 4-h exposure to 2 ppm ozone. Treatment with ebselen (10 mg/kg) significantly decreased Pulmonary Inflammation as indicated by the albumin concentration and the number of neutrophils in the bronchoalveolar lavage fluid 18 h after the ozone exposure. Although treatment with ebselen did not alter the macrophage expression of inducible nitric oxide synthase after the ozone exposure, it did markedly inhibit the nitration reaction of tyrosine residues, suggesting that ebselen scavenges peroxynitrite during ozone-induced Pulmonary Inflammation. Treatment with ebselen also enhanced the Pulmonary expression of both copper, zinc, and manganous superoxide dismutases at the same time point. These enzymes may also contribute to a decrease in the formation of peroxynitrite by lowering the concentration of superoxide. Thus, ebselen represents a useful compound for protecting against certain acute lung injuries by modulating the oxidant-related inflammatory process.
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Elimination of neutrophils by apoptosis during the resolution of acute Pulmonary Inflammation in rats.
Lung, 1998Co-Authors: Yukio Ishii, Akihiro Nomura, Tohru Sakamoto, Yoshiyuki Uchida, K. Hashimoto, Morio Ohtsuka, Shizuo Hasegawa, Masaru SagaiAbstract:We evaluated the apoptosis of neutrophils during the resolution of acute Pulmonary Inflammation induced by exposure to ozone. The inflammatory response was assessed in rat lungs 0, 1, 3, and 7 days after 4-h exposure to air or 2 ppm ozone. Analysis of bronchoalveolar lavage fluid demonstrated significant increases in albumin concentrations on days 0 and 1 and in the number of lavageable neutrophils on days 0, 1, and 3, indicating the presence of acute Pulmonary Inflammation. These parameters returned to control values on day 7, which suggests that the acute Pulmonary Inflammation induced by ozone was reversible. On days 1 and 3, but not on day 0, the neutrophils showed morphologic evidence of apoptosis. Based on morphologic analysis, the proportion of apoptotic neutrophils was 23.3 ± 2.2% on day 1 and 55.7 ± 3.2% on day 3. Terminal deoxynucleotidyl transferase-mediated dUTP end labeling (TUNEL), in contrast, revealed that the proportion of apoptotic cells was 59.7 ± 9.1% on day 1 and 68.0 ± 4.3% on day 3. On day 3, light microscopy and electron microscopy demonstrated engulfment of the neutrophils by macrophages. These findings indicate that the apoptosis of neutrophils followed by their engulfment by macrophages contributes to the clearance of neutrophils from the sites of Inflammation. Moreover, TUNEL detected apoptotic neutrophils with greater sensitivity compared with morphologic assessment.
Yukio Ishii - One of the best experts on this subject based on the ideXlab platform.
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Aggravation of Bleomycin-Induced Pulmonary Inflammation and Fibrosis in Mice Lacking Peroxiredoxin I
American journal of respiratory cell and molecular biology, 2011Co-Authors: Norihiro Kikuchi, Yukio Ishii, Yuko Morishima, Tohru Sakamoto, Yuichi Yageta, Norihiro Haraguchi, Tadahiro Yamadori, Hironori Masuko, Toru Yanagawa, Eiji WarabiAbstract:Oxidative stress plays an important role in the pathogenesis of acute lung injury and Pulmonary fibrosis. Peroxiredoxin (Prx) I is a cellular antioxidant enzyme induced under stress conditions. In the present study, the protective effects of Prx I on the development of bleomycin-induced acute Pulmonary Inflammation and Pulmonary fibrosis were investigated using Prx I–deficient mice. Survival of Prx I–deficient mice after bleomycin administration was significantly lower than that of wild-type mice, corresponding with enhanced acute Pulmonary Inflammation and fibrosis. The level of inflammatory cytokines and chemokines, such as TNF-α, macrophage inflammatory protein-2, and monocyte chemotactic protein-1, was significantly elevated in the bronchoalveolar lavage fluid of Prx I–deficient mice after bleomycin administration. Furthermore, the level of 8-isoprostane, an oxidative stress marker, and the concentration and alveolar macrophage expression of macrophage migration inhibitory factor were elevated in the ...
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Ebselen decreases ozone-induced Pulmonary Inflammation in rats.
Lung, 2000Co-Authors: Yukio Ishii, Ken-ichi Hashimoto, Kuniyoshi Hirano, Yuko Morishima, Mie Mochizuki, Kuniko Masuyama, Akihiro Nomura, Tohru Sakamoto, Yoshiyuki Uchida, Masaru SagaiAbstract:We studied the effects of ebselen on rat lung inflammatory responses against ozone exposure. Rats were treated with ebselen every 12 h from 1 h before a single 4-h exposure to 2 ppm ozone. Treatment with ebselen (10 mg/kg) significantly decreased Pulmonary Inflammation as indicated by the albumin concentration and the number of neutrophils in the bronchoalveolar lavage fluid 18 h after the ozone exposure. Although treatment with ebselen did not alter the macrophage expression of inducible nitric oxide synthase after the ozone exposure, it did markedly inhibit the nitration reaction of tyrosine residues, suggesting that ebselen scavenges peroxynitrite during ozone-induced Pulmonary Inflammation. Treatment with ebselen also enhanced the Pulmonary expression of both copper, zinc, and manganous superoxide dismutases at the same time point. These enzymes may also contribute to a decrease in the formation of peroxynitrite by lowering the concentration of superoxide. Thus, ebselen represents a useful compound for protecting against certain acute lung injuries by modulating the oxidant-related inflammatory process.
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Elimination of neutrophils by apoptosis during the resolution of acute Pulmonary Inflammation in rats.
Lung, 1998Co-Authors: Yukio Ishii, Akihiro Nomura, Tohru Sakamoto, Yoshiyuki Uchida, K. Hashimoto, Morio Ohtsuka, Shizuo Hasegawa, Masaru SagaiAbstract:We evaluated the apoptosis of neutrophils during the resolution of acute Pulmonary Inflammation induced by exposure to ozone. The inflammatory response was assessed in rat lungs 0, 1, 3, and 7 days after 4-h exposure to air or 2 ppm ozone. Analysis of bronchoalveolar lavage fluid demonstrated significant increases in albumin concentrations on days 0 and 1 and in the number of lavageable neutrophils on days 0, 1, and 3, indicating the presence of acute Pulmonary Inflammation. These parameters returned to control values on day 7, which suggests that the acute Pulmonary Inflammation induced by ozone was reversible. On days 1 and 3, but not on day 0, the neutrophils showed morphologic evidence of apoptosis. Based on morphologic analysis, the proportion of apoptotic neutrophils was 23.3 ± 2.2% on day 1 and 55.7 ± 3.2% on day 3. Terminal deoxynucleotidyl transferase-mediated dUTP end labeling (TUNEL), in contrast, revealed that the proportion of apoptotic cells was 59.7 ± 9.1% on day 1 and 68.0 ± 4.3% on day 3. On day 3, light microscopy and electron microscopy demonstrated engulfment of the neutrophils by macrophages. These findings indicate that the apoptosis of neutrophils followed by their engulfment by macrophages contributes to the clearance of neutrophils from the sites of Inflammation. Moreover, TUNEL detected apoptotic neutrophils with greater sensitivity compared with morphologic assessment.
Andrij Holian - One of the best experts on this subject based on the ideXlab platform.
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Therapeutic treatment of dietary docosahexaenoic acid for particle-induced Pulmonary Inflammation in Balb/c mice
Inflammation Research, 2021Co-Authors: Paige Fletcher, Raymond F. Hamilton, Joseph F. Rhoderick, Britten Postma, Mary Buford, James J. Pestka, Andrij HolianAbstract:Objective and design The omega-3 polyunsaturated fatty acid docosahexaenoic acid (DHA) has been reported to suppress Inflammation. Pulmonary Inflammation can be directly linked to exposure of various occupational and man-made particles leading to Pulmonary diseases. Therapeutic treatments are lacking for particle-induced Pulmonary Inflammation. These studies evaluated DHA as a therapeutic treatment for semi-acute and chronic particle-induced Pulmonary Inflammation. Methods Balb/c mice were oropharyngeal instilled with hydrophobic multi-walled carbon nanotube (MWCNT) or hydrophilic crystalline silica (SiO_2) either as one instillation (semi-acute) or once a week for 4 weeks (chronic). One week later, the mice were placed on either a control or 1% DHA-containing diet for 3 weeks (semi-acute) or 12 weeks (chronic). Mice were assessed for inflammatory signaling within the lung lavage fluid, impact on phagolysosomal membrane permeability, shifts of macrophage phenotype gene expression (M1, M2a, M2b, and M2c), and Pulmonary histopathology. Results DHA increased Pulmonary inflammatory markers and lung pathology when mice were exposed to SiO_2. There were trending decreases of inflammatory markers for MWCNT-exposed mice with DHA treatment, however, mostly not statistically significant. Conclusion The anti-inflammatory benefits of DHA treatment depend upon the type of inflammatory particle, magnitude of Inflammation, and duration of treatment.
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Protection against ozone-induced Pulmonary Inflammation and cell death by endotoxin pretreatment in mice: role of HO-1.
Inhalation toxicology, 2000Co-Authors: Raymond F. Hamilton, Andrij HolianAbstract:Ozone is a ubiquitous air pollutant that can cause acute Pulmonary Inflammation and cell injury and may contribute to the exacerbation of chronic Pulmonary diseases. The molecular mechanisms of ozone-induced cell injury, as well as protective mechanisms against ozone-injury, are not well understood. Since ozone is a reactive oxidant, and heme oxygenase-1 (HO-1) is an antioxidant enzyme induced by many oxidative stimuli, we hypothesized that HO-1 is one of the protective mechanisms against ozoneinduced cell injury, as well as Pulmonary Inflammation. In the current study, C57Bl/6 mice were pretreated with a low level of endotoxin (lipopolysaccharide, LPS) (0.5 mg/kg) to induce HO-1, and 16 h later were exposed to 1 ppm ozone for 3 h. Endotoxin pretreatment caused a significant protection against ozone-induced Pulmonary Inflammation and cell injury in bronchoalveolar lavage (BAL) cells. The protection by endotoxin pretreatment against ozone-induced Inflammation and necrosis in BAL cells was abolished by the ...
Peter Rosenberger - One of the best experts on this subject based on the ideXlab platform.
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Semaphorin 7A Aggravates Pulmonary Inflammation during Lung Injury.
PloS one, 2016Co-Authors: Judith M. Roth, David Köhler, Mariella Schneider, Tiago Granja, Peter RosenbergerAbstract:The extent of Pulmonary Inflammation during lung injury ultimately determines patient outcome. Pulmonary Inflammation is initiated by the migration of neutrophils into the alveolar space. Recent work has demonstrated that the guidance protein semaphorin 7A (SEMA7A) influences the migration of neutrophils into hypoxic tissue sites, yet, its role during lung injury is not well understood. Here, we report that the expression of SEMA7A is induced in vitro through pro-inflammatory cytokines. SEMA7A itself induces the production of pro-inflammatory cytokines in endothelial and epithelial cells, enhancing Pulmonary Inflammation. The induction of SEMA7A facilitates the transendothelial migration of neutrophils. In vivo, animals with deletion of SEMA7A expression showed reduced signs of Pulmonary inflammatory changes following lipopolysaccharide challenge. We define here the role of SEMA7A in the development of lung injury and identify a potential pathway to interfere with these detrimental changes. Future anti-inflammatory strategies for the treatment of lung injury might be based on this finding.
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Rosiglitazone Dampens Pulmonary Inflammation in a Porcine Model of Acute Lung Injury
Inflammation, 2014Co-Authors: Valbona Mirakaj, Christian Mutz, Dierk A. Vagts, Janek Henes, Helene A. Haeberle, Susanne Husung, Tony König, Gabriele Nöldge-schomburg, Peter RosenbergerAbstract:The hallmarks of acute lung injury (ALI) are the compromised alveolar-capillary barrier and the extravasation of leukocytes into the alveolar space. Given the fact that the peroxisome proliferator-activated receptor-γ agonist rosiglitazone holds significant anti-inflammatory properties, we aimed to evaluate whether rosiglitazone could dampen these hallmarks of local Pulmonary Inflammation in a porcine model of lung injury. For this purpose, we used a model of lipopolysaccharide (LPS, 50 μg/kg)-induced ALI. One hundred twenty minutes following the infusion of LPS, we started the exposure to rosiglitazone through inhalation or infusion. We found that intravenous rosiglitazone significantly controlled local Pulmonary Inflammation as determined through the expression of cytokines within the alveolar compartment. Furthermore, we found a significant reduction of the protein concentration and neutrophil activity within the alveolar space. In summary, we therefore conclude that the treatment with rosiglitazone might dampen local Pulmonary Inflammation during the initial stages of ALI.
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Crucial role of Plexin C1 for Pulmonary Inflammation and survival during lung injury.
Mucosal immunology, 2013Co-Authors: Tiago Granja, David Köhler, Valbona Mirakaj, E Nelson, Klemens König, Peter RosenbergerAbstract:Acute Pulmonary Inflammation during lung injury is initiated by the migration of neutrophils into the alveolar space. The severity of these inflammatory changes within the Pulmonary tissue determines the severity of lung injury and ultimately patient outcome. Recent work has demonstrated that the guidance protein Semaphorin 7A propagates the infiltration of neutrophils into an hypoxic tissue site, yet the role of its target receptor Plexin C1 (PLXNC1) during lung injury is to date unknown. We demonstrate here that PLXNC1(+) neutrophils are present within the alveolar space and that PLXNC1 is induced in vitro and in vivo during lung injury. In a model of high-pressure ventilation PLXNC1(-/-) animals show decreased signs of alveolar Inflammation and improved survival compared with wild-type controls. Studies employing chimeric animals identified the hematopoietic expression of PLXNC1 to be of crucial importance for the observed results. Functional inhibition of PLXNC1 resulted in improved survival and ameliorated the signs of Inflammation within the lung. Furthermore, the injection of a peptide binding to PLXNC1 resulted in improved survival and attenuated Pulmonary Inflammation. As such we demonstrate here, that previously unknown PLXNC1 holds significant importance for degree of Pulmonary Inflammation and determines outcome during experimental lung injury.
