The Experts below are selected from a list of 27 Experts worldwide ranked by ideXlab platform
Leo E. Otterbein - One of the best experts on this subject based on the ideXlab platform.
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Biliverdin administration protects against endotoxin-induced acute Lung injury in rats.
American journal of physiology. Lung cellular and molecular physiology, 2005Co-Authors: Judit K. Sarady-andrews, Fang Liu, David A. Gallo, Atsunori Nakao, Marcus Overhaus, Robert Öllinger, Augustine M.k. Choi, Leo E. OtterbeinAbstract:Given the high morbidity and mortality rates associated with pulmonary inflammation in sepsis, there is a pressing need for new therapeutic modalities to prevent acute respiratory distress. The enzyme heme oxygenase-1 (HO-1) provides potent cytoprotection against Lung injury; however, the mechanism by which it does so is unclear. HO-1 catabolizes heme into biliverdin (BV), which is rapidly converted to bilirubin by BV reductase. We tested the hypothesis that BV administration could substitute for the effects observed with HO-1. Using the well-described rat model of LPS-induced shock, we demonstrate that exposure to BV imparts a potent defense against lethal endotoxemia systemically, as well as in the Lungs, and effectively abrogates the inflammatory response. BV administration before a lethal dose of LPS leads to a significant improvement in long-term survival: 87% vs. 20% in sham-treated controls. BV treatment suppressed LPS-induced increases in Lung permeability and Lung Alveolitis and significantly reduced serum levels of the LPS-induced proinflammatory cytokine IL-6. Moreover, bilirubin administered just after LPS also abrogated Lung inflammation. BV treatment also augmented expression of the anti-inflammatory cytokine IL-10. Similar effects on production were observed with BV treatment in vitro in mouse Lung endothelial cells and RAW 264.7 macrophages treated with LPS. In conclusion, these data demonstrate that BV can modulate the inflammatory response and suppress pathophysiological changes in the Lung and may therefore have therapeutic application in inflammatory disease states of the Lung.
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carbon monoxide protection against endotoxic shock involves reciprocal effects on inos in the Lung and liver
The FASEB Journal, 2004Co-Authors: Judit K Sarady, Augustine M.k. Choi, Brian S Zuckerbraun, Martin Bilban, Oswald Wagner, Anny Usheva, Emeka Ifedigbo, Ruben Zamora, Leo E. OtterbeinAbstract:Carbon monoxide (CO) has recently emerged as having potent cytoprotective properties; the mechanisms underlying these effects, however, are just beginning to be elucidated. In a rat model of lipopolysaccharide (LPS)-induced multiorgan failure, we demonstrate that exposure to a low concentration of CO for only 1 h imparts a potent defense against lethal endotoxemia and effectively abrogates the inflammatory response. Exposure to CO leads to long-term survival of >80% of animals vs. 20% in controls. In the Lung, CO suppressed LPS-induced Lung Alveolitis and associated edema formation, while in the liver, it reduced expression of serum alanine aminotransferase, a marker of liver injury. This protection appears to be based in part on different mechanisms in the Lung and liver in that CO had reciprocal effects on LPS-induced expression of iNOS and NO production, important mediators in the response to LPS. CO prevented the up-regulation of iNOS and NO in the Lung while augmenting expression of iNOS and NO in the liver. Studies of primary Lung macrophages and hepatocytes in vitro revealed a similar effect; CO inhibited LPS-induced cytokine production in Lung macrophages while reducing LPS-induced iNOS expression and nitrite accumulation and protected hepatocytes from apoptosis while augmenting iNOS expression. Although it is unclear to which extent these changes in iNOS contribute to the cytoprotection conferred by CO, it is fascinating that in each organ CO influences iNOS in a manner known to be protective in that organ: NO is therapeutic in the liver while it is damaging in the Lung.
Richard D Ye - One of the best experts on this subject based on the ideXlab platform.
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identification of p rex1 as an anti inflammatory and anti fibrogenic target for pulmonary fibrosis
Scientific Reports, 2016Co-Authors: Qing Liang, Ni Cheng, Gufang Zhang, Yurong Liang, Feng Qian, Dianqing Wu, Richard D YeAbstract:Pulmonary fibrosis (PF) is a chronic disorder that leads to progressive loss of Lung functions with a high mortality rate. PF may be a consequence of radiation, chemotherapy and occupational inhalation of dust particle, or without a clearly identifiable cause (idiopathic pulmonary fibrosis, IPF)1. All forms of PF are characterized by increased synthesis and deposit of extracellular matrix (ECM) proteins including collagen and fibronectin, accompanied by elevated production of transforming growth factor β 1 (TGF-β1) and increased proliferation of interstitial fibroblasts2. Despite detailed characterization of the pathological changes in PF, however, an effective cure for PF remains elusive. Hence, identification of novel targets for PF is crucial to the development of therapies for PF. Several mouse models have been developed for research on PF3. Among these models, bleomycin-induced fibrosis in rodents has been widely used in research laboratories. Bleomycin is an antineoplastic drug that binds DNA4. Intratracheal administration of bleomycin results in cell death within 24 hours. On days 2 and 3 following bleomycin administration, inflammation of the Lung (Alveolitis) occurs and is gradually developed into interstitial inflammation on days 4–12. The fibrogenic response, characterized with fibroblast proliferation and increased production of ECM proteins, begins on day 4 after bleomycin administration and culminates on Day 215. Using this model, several factors that affect the inflammatory and fibrogenic phases of PF have been identified. For instance, the use of the bleomycin-induced PF model has accelerated our understanding of the in vivo functions of TGF-β1 in fibrosis6. One of the limiting factors in developing an effective therapy for PF is the lack of understanding of the transition from the inflammatory phase to the fibrogenic phase. Multiple factors contribute to the development of IPF, but many of them, including TGF-β and Smad 3, are not suitable targets for long-term drug intervention due to their pleotropic functions6. We investigated whether P-Rex1, a PI3K- and Gβγ-regulated guanine nucleotide exchange factor (GEF) known for its roles in the activation of Rac7,8, is involved in the development of PF in bleomycin-treated mice. P-Rex1 is a Dbl-family GEF initially identified in neutrophils and neurons7. Its functions in the regulation of the inflammatory response (reviewed in8) led us to investigate a potential role for P-Rex1 in the development of PF. Our work show that P-Rex1 is not only involved in the inflammatory response resulting from bleomycin-induced Lung damage, but also contributes to the fibrogenic response of PF by acting as a downstream effector for TGF-β1 signaling. Mouse survival assay and histological analysis indicate that genetic deletion of p-rex1 offers protection against bleomycin-induced PF, as evidenced by reduced TGF-β1 production, abrogated fibroblast migration and reduced mortality. These findings offer the possibility of targeting P-Rex1 for PF therapy based on its dual functions in the inflammatory and fibrogenic processes.
Augustine M.k. Choi - One of the best experts on this subject based on the ideXlab platform.
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Biliverdin administration protects against endotoxin-induced acute Lung injury in rats.
American journal of physiology. Lung cellular and molecular physiology, 2005Co-Authors: Judit K. Sarady-andrews, Fang Liu, David A. Gallo, Atsunori Nakao, Marcus Overhaus, Robert Öllinger, Augustine M.k. Choi, Leo E. OtterbeinAbstract:Given the high morbidity and mortality rates associated with pulmonary inflammation in sepsis, there is a pressing need for new therapeutic modalities to prevent acute respiratory distress. The enzyme heme oxygenase-1 (HO-1) provides potent cytoprotection against Lung injury; however, the mechanism by which it does so is unclear. HO-1 catabolizes heme into biliverdin (BV), which is rapidly converted to bilirubin by BV reductase. We tested the hypothesis that BV administration could substitute for the effects observed with HO-1. Using the well-described rat model of LPS-induced shock, we demonstrate that exposure to BV imparts a potent defense against lethal endotoxemia systemically, as well as in the Lungs, and effectively abrogates the inflammatory response. BV administration before a lethal dose of LPS leads to a significant improvement in long-term survival: 87% vs. 20% in sham-treated controls. BV treatment suppressed LPS-induced increases in Lung permeability and Lung Alveolitis and significantly reduced serum levels of the LPS-induced proinflammatory cytokine IL-6. Moreover, bilirubin administered just after LPS also abrogated Lung inflammation. BV treatment also augmented expression of the anti-inflammatory cytokine IL-10. Similar effects on production were observed with BV treatment in vitro in mouse Lung endothelial cells and RAW 264.7 macrophages treated with LPS. In conclusion, these data demonstrate that BV can modulate the inflammatory response and suppress pathophysiological changes in the Lung and may therefore have therapeutic application in inflammatory disease states of the Lung.
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carbon monoxide protection against endotoxic shock involves reciprocal effects on inos in the Lung and liver
The FASEB Journal, 2004Co-Authors: Judit K Sarady, Augustine M.k. Choi, Brian S Zuckerbraun, Martin Bilban, Oswald Wagner, Anny Usheva, Emeka Ifedigbo, Ruben Zamora, Leo E. OtterbeinAbstract:Carbon monoxide (CO) has recently emerged as having potent cytoprotective properties; the mechanisms underlying these effects, however, are just beginning to be elucidated. In a rat model of lipopolysaccharide (LPS)-induced multiorgan failure, we demonstrate that exposure to a low concentration of CO for only 1 h imparts a potent defense against lethal endotoxemia and effectively abrogates the inflammatory response. Exposure to CO leads to long-term survival of >80% of animals vs. 20% in controls. In the Lung, CO suppressed LPS-induced Lung Alveolitis and associated edema formation, while in the liver, it reduced expression of serum alanine aminotransferase, a marker of liver injury. This protection appears to be based in part on different mechanisms in the Lung and liver in that CO had reciprocal effects on LPS-induced expression of iNOS and NO production, important mediators in the response to LPS. CO prevented the up-regulation of iNOS and NO in the Lung while augmenting expression of iNOS and NO in the liver. Studies of primary Lung macrophages and hepatocytes in vitro revealed a similar effect; CO inhibited LPS-induced cytokine production in Lung macrophages while reducing LPS-induced iNOS expression and nitrite accumulation and protected hepatocytes from apoptosis while augmenting iNOS expression. Although it is unclear to which extent these changes in iNOS contribute to the cytoprotection conferred by CO, it is fascinating that in each organ CO influences iNOS in a manner known to be protective in that organ: NO is therapeutic in the liver while it is damaging in the Lung.
Nannan Liu - One of the best experts on this subject based on the ideXlab platform.
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Effect of Feining on bleomycin-induced pulmonary injuries in rats.
Journal of ethnopharmacology, 2011Co-Authors: Xiangyan Liang, Qiong Tian, Zhangrui Wei, Fang-e Liu, Jiankang Chen, Yufeng Zhao, Xiaojun Huang, Xingchun Zhou, Nannan LiuAbstract:Abstract Ethnopharmacological relevance The flowers of Gentiana veitchiorum has been widely used in decoction form in the traditional medicine of Tibet against tussis, tracheitis, angina for their anti-inflammatory, antimicrobial and alexipharmic properties. Aim of the study The aim of current study was to evaluate the therapeutic effects of Feining, a Chinese herbal formula (national invention patent: ZL200510042636.3) against pulmonary injuries and to clarify the mechanisms involved. Materials and methods Experimental pulmonary injuries were induced by bleomycin (BLM) in rats with or without subsequent treatment of Feining or prednisone as positive control. The pulmonary injuries were evaluated by histological analysis. Also, the levels of superoxide dismutase (SOD), malondialdehyde (MDA), glutathione (GSH) and hydroxyproline (Hyp) in the Lung tissue were determined. To clarify one of the possible active principles responsible for Feining, high performance liquid chromatography–diode array detector–mass spectrometry (HPLC–DAD–MS) method was applied to identify the components of Gentiana veitchiorum , one of major ingredients of Feining. Results Feining significantly improved Lung Alveolitis scores and reduced the Hyp content of Lungs, which is an index of collagen accumulation. Moreover, Feining played a role against the oxidative damages by decreasing the MDA level, whereas increasing SOD and GSH activity, which correlated with oxidation resistance and scavenging of free radicals. In addition, Feining alleviated inflammatory Lung injury by decreasing tumor necrosis factor-α (TNF-α) expression. HPLC–DAD–MS analysis revealed that there was 1.97% gentiopicroside in Gentiana veitchiorum . Conclusion Feining has certain therapeutic effects against pulmonary injuries.
Judit K. Sarady-andrews - One of the best experts on this subject based on the ideXlab platform.
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Biliverdin administration protects against endotoxin-induced acute Lung injury in rats.
American journal of physiology. Lung cellular and molecular physiology, 2005Co-Authors: Judit K. Sarady-andrews, Fang Liu, David A. Gallo, Atsunori Nakao, Marcus Overhaus, Robert Öllinger, Augustine M.k. Choi, Leo E. OtterbeinAbstract:Given the high morbidity and mortality rates associated with pulmonary inflammation in sepsis, there is a pressing need for new therapeutic modalities to prevent acute respiratory distress. The enzyme heme oxygenase-1 (HO-1) provides potent cytoprotection against Lung injury; however, the mechanism by which it does so is unclear. HO-1 catabolizes heme into biliverdin (BV), which is rapidly converted to bilirubin by BV reductase. We tested the hypothesis that BV administration could substitute for the effects observed with HO-1. Using the well-described rat model of LPS-induced shock, we demonstrate that exposure to BV imparts a potent defense against lethal endotoxemia systemically, as well as in the Lungs, and effectively abrogates the inflammatory response. BV administration before a lethal dose of LPS leads to a significant improvement in long-term survival: 87% vs. 20% in sham-treated controls. BV treatment suppressed LPS-induced increases in Lung permeability and Lung Alveolitis and significantly reduced serum levels of the LPS-induced proinflammatory cytokine IL-6. Moreover, bilirubin administered just after LPS also abrogated Lung inflammation. BV treatment also augmented expression of the anti-inflammatory cytokine IL-10. Similar effects on production were observed with BV treatment in vitro in mouse Lung endothelial cells and RAW 264.7 macrophages treated with LPS. In conclusion, these data demonstrate that BV can modulate the inflammatory response and suppress pathophysiological changes in the Lung and may therefore have therapeutic application in inflammatory disease states of the Lung.
