The Experts below are selected from a list of 37236 Experts worldwide ranked by ideXlab platform
Akinori Arimura - One of the best experts on this subject based on the ideXlab platform.
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antifibrotic action of pirfenidone and prednisolone different effects on pulmonary cytokines and growth factors in bleomycin induced murine pulmonary fibrosis
2008Co-Authors: Hisashi Oku, Toshikatsu Shimizu, Tomoji Kawabata, Morio Nagira, Ichiro Hikita, Azumi Ueyama, Shuuichi Matsushima, Mikinori Torii, Akinori ArimuraAbstract:Pirfenidone, a broad-spectrum antifibrotic agent, is known to have efficacy in certain fibrotic disease models, and is under clinical trials in patients with idiopathic pulmonary fibrosis. We investigated the antifibrotic effect of pirfenidone, and its regulatory effect on various pulmonary cytokines, in bleomycin-induced lung fibrosis in mice at the protein level, using prednisolone as a reference agent. Pirfenidone attenuated the bleomycin-induced pulmonary fibrosis at a minimum effective dose of 30 mg/kg/day t.i.d. from the analysis of lung hydroxyproline content. Both pirfenidone (30, 100 mg/kg/day t.i.d) and prednisolone (3, 15 mg/kg/day q.d.) suppressed lung inflammatory edema; however, prednisolone failed to suppress pulmonary fibrosis, which was significantly suppressed only by pirfenidone. Both pirfenidone and prednisolone suppressed the increase in lung interleukin (IL)-1beta, IL-6, IL-12p40 and monocyte chemoattractant protein (MCP)-1 levels induced by bleomycin. On the other hand, pirfenidone prevented the bleomycin-induced decrease in lung interferon (IFN)-gamma levels, while prednisolone had no such effect. Furthermore, pirfenidone suppressed elevation of lung basic-fibroblast growth factor (bFGF) and transforming growth factor (TGF)-beta1 levels, but prednisolone had no such effect. The increases in lung Stroma Cell derived factor (SDF)-1alpha and IL-18 were also suppressed. These findings suggest that pirfenidone exerts its antifibrotic effect through regulation of lung IFN-gamma, bFGF and TGF-beta1 levels during the development of bleomycin-induced pulmonary fibrosis in mice. The effect on SDF-1alpha and IL-18 levels may also be related to the antifibrotic effects of pirfenidone.
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antifibrotic action of pirfenidone and prednisolone different effects on pulmonary cytokines and growth factors in bleomycin induced murine pulmonary fibrosis
2008Co-Authors: Toshikatsu Shimizu, Tomoji Kawabata, Morio Nagira, Ichiro Hikita, Azumi Ueyama, Shuuichi Matsushima, Mikinori Torii, Akinori ArimuraAbstract:Abstract Pirfenidone, a broad-spectrum antifibrotic agent, is known to have efficacy in certain fibrotic disease models, and is under clinical trials in patients with idiopathic pulmonary fibrosis. We investigated the antifibrotic effect of pirfenidone, and its regulatory effect on various pulmonary cytokines, in bleomycin-induced lung fibrosis in mice at the protein level, using prednisolone as a reference agent. Pirfenidone attenuated the bleomycin-induced pulmonary fibrosis at a minimum effective dose of 30 mg/kg/day t.i.d. from the analysis of lung hydroxyproline content. Both pirfenidone (30, 100 mg/kg/day t.i.d) and prednisolone (3, 15 mg/kg/day q.d.) suppressed lung inflammatory edema; however, prednisolone failed to suppress pulmonary fibrosis, which was significantly suppressed only by pirfenidone. Both pirfenidone and prednisolone suppressed the increase in lung interleukin (IL)-1β, IL-6, IL-12p40 and monocyte chemoattractant protein (MCP)-1 levels induced by bleomycin. On the other hand, pirfenidone prevented the bleomycin-induced decrease in lung interferon (IFN)-γ levels, while prednisolone had no such effect. Furthermore, pirfenidone suppressed elevation of lung basic-fibroblast growth factor (bFGF) and transforming growth factor (TGF)-β1 levels, but prednisolone had no such effect. The increases in lung Stroma Cell derived factor (SDF)-1α and IL-18 were also suppressed. These findings suggest that pirfenidone exerts its antifibrotic effect through regulation of lung IFN-γ, bFGF and TGF-β1 levels during the development of bleomycin-induced pulmonary fibrosis in mice. The effect on SDF-1α and IL-18 levels may also be related to the antifibrotic effects of pirfenidone.
Toshikatsu Shimizu - One of the best experts on this subject based on the ideXlab platform.
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antifibrotic action of pirfenidone and prednisolone different effects on pulmonary cytokines and growth factors in bleomycin induced murine pulmonary fibrosis
2008Co-Authors: Hisashi Oku, Toshikatsu Shimizu, Tomoji Kawabata, Morio Nagira, Ichiro Hikita, Azumi Ueyama, Shuuichi Matsushima, Mikinori Torii, Akinori ArimuraAbstract:Pirfenidone, a broad-spectrum antifibrotic agent, is known to have efficacy in certain fibrotic disease models, and is under clinical trials in patients with idiopathic pulmonary fibrosis. We investigated the antifibrotic effect of pirfenidone, and its regulatory effect on various pulmonary cytokines, in bleomycin-induced lung fibrosis in mice at the protein level, using prednisolone as a reference agent. Pirfenidone attenuated the bleomycin-induced pulmonary fibrosis at a minimum effective dose of 30 mg/kg/day t.i.d. from the analysis of lung hydroxyproline content. Both pirfenidone (30, 100 mg/kg/day t.i.d) and prednisolone (3, 15 mg/kg/day q.d.) suppressed lung inflammatory edema; however, prednisolone failed to suppress pulmonary fibrosis, which was significantly suppressed only by pirfenidone. Both pirfenidone and prednisolone suppressed the increase in lung interleukin (IL)-1beta, IL-6, IL-12p40 and monocyte chemoattractant protein (MCP)-1 levels induced by bleomycin. On the other hand, pirfenidone prevented the bleomycin-induced decrease in lung interferon (IFN)-gamma levels, while prednisolone had no such effect. Furthermore, pirfenidone suppressed elevation of lung basic-fibroblast growth factor (bFGF) and transforming growth factor (TGF)-beta1 levels, but prednisolone had no such effect. The increases in lung Stroma Cell derived factor (SDF)-1alpha and IL-18 were also suppressed. These findings suggest that pirfenidone exerts its antifibrotic effect through regulation of lung IFN-gamma, bFGF and TGF-beta1 levels during the development of bleomycin-induced pulmonary fibrosis in mice. The effect on SDF-1alpha and IL-18 levels may also be related to the antifibrotic effects of pirfenidone.
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antifibrotic action of pirfenidone and prednisolone different effects on pulmonary cytokines and growth factors in bleomycin induced murine pulmonary fibrosis
2008Co-Authors: Toshikatsu Shimizu, Tomoji Kawabata, Morio Nagira, Ichiro Hikita, Azumi Ueyama, Shuuichi Matsushima, Mikinori Torii, Akinori ArimuraAbstract:Abstract Pirfenidone, a broad-spectrum antifibrotic agent, is known to have efficacy in certain fibrotic disease models, and is under clinical trials in patients with idiopathic pulmonary fibrosis. We investigated the antifibrotic effect of pirfenidone, and its regulatory effect on various pulmonary cytokines, in bleomycin-induced lung fibrosis in mice at the protein level, using prednisolone as a reference agent. Pirfenidone attenuated the bleomycin-induced pulmonary fibrosis at a minimum effective dose of 30 mg/kg/day t.i.d. from the analysis of lung hydroxyproline content. Both pirfenidone (30, 100 mg/kg/day t.i.d) and prednisolone (3, 15 mg/kg/day q.d.) suppressed lung inflammatory edema; however, prednisolone failed to suppress pulmonary fibrosis, which was significantly suppressed only by pirfenidone. Both pirfenidone and prednisolone suppressed the increase in lung interleukin (IL)-1β, IL-6, IL-12p40 and monocyte chemoattractant protein (MCP)-1 levels induced by bleomycin. On the other hand, pirfenidone prevented the bleomycin-induced decrease in lung interferon (IFN)-γ levels, while prednisolone had no such effect. Furthermore, pirfenidone suppressed elevation of lung basic-fibroblast growth factor (bFGF) and transforming growth factor (TGF)-β1 levels, but prednisolone had no such effect. The increases in lung Stroma Cell derived factor (SDF)-1α and IL-18 were also suppressed. These findings suggest that pirfenidone exerts its antifibrotic effect through regulation of lung IFN-γ, bFGF and TGF-β1 levels during the development of bleomycin-induced pulmonary fibrosis in mice. The effect on SDF-1α and IL-18 levels may also be related to the antifibrotic effects of pirfenidone.
Matthew Bogyo - One of the best experts on this subject based on the ideXlab platform.
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tumor Cell derived and macrophage derived cathepsin b promotes progression and lung metastasis of mammary cancer
2006Co-Authors: Olga Vasiljeva, Anna Papazoglou, Achim Kruger, Harald Brodoefel, Matvey Korovin, Jan M Deussing, Nicole H Augustin, Boye Schnack Nielsen, Kasper Almholt, Matthew BogyoAbstract:Proteolysis in close vicinity of tumor Cells is a hallmark of cancer invasion and metastasis. We show here that mouse mammary tumor virus-polyoma middle T antigen (PyMT) transgenic mice deficient for the cysteine protease cathepsin B (CTSB) exhibited a significantly delayed onset and reduced growth rate of mammary cancers compared with wild-type PyMT mice. Lung metastasis volumes were significantly reduced in PyMT;ctsb(+/-), an effect that was not further enhanced in PyMT;ctsb(-/-) mice. Furthermore, lung colonization studies of PyMT Cells with different CTSB genotypes injected into congenic wild-type mice and in vitro Matrigel invasion assays confirmed a specific role for tumor-derived CTSB in invasion and metastasis. Interestingly, Cell surface labeling of cysteine cathepsins by the active site probe DCG-04 detected up-regulation of cathepsin X on PyMT;ctsb(-/-) Cells. Treatment of Cells with a neutralizing anti-cathepsin X antibody significantly reduced Matrigel invasion of PyMT;ctsb(-/-) Cells but did not affect invasion of PyMT;ctsb(+/+) or PyMT;ctsb(+/-) Cells, indicating a compensatory function of cathepsin X in CTSB-deficient tumor Cells. Finally, an adoptive transfer model, in which ctsb(+/+), ctsb(+/-), and ctsb(-/-) recipient mice were challenged with PyMT;ctsb(+/+) Cells, was used to address the role of Stroma-derived CTSB in lung metastasis formation. Notably, ctsb(-/-) mice showed reduced number and volume of lung colonies, and infiltrating macrophages showed a strongly up-regulated expression of CTSB within metastatic Cell populations. These results indicate that both cancer Cell-derived and Stroma Cell-derived (i.e., macrophages) CTSB plays an important role in tumor progression and metastasis.
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tumor Cell derived and macrophage derived cathepsin b promotes progression and lung metastasis of mammary cancer
2006Co-Authors: Olga Vasiljeva, Anna Papazoglou, Achim Kruger, Harald Brodoefel, Matvey Korovin, Jan M Deussing, Nicole H Augustin, Boye Schnack Nielsen, Kasper Almholt, Matthew BogyoAbstract:Proteolysis in close vicinity of tumor Cells is a hallmark of cancer invasion and metastasis. We show here that mouse mammary tumor virus–polyoma middle T antigen (PyMT) transgenic mice deficient for the cysteine protease cathepsin B (CTSB) exhibited a significantly delayed onset and reduced growth rate of mammary cancers compared with wild-type PyMT mice. Lung metastasis volumes were significantly reduced in PyMT;ctsb +/− , an effect that was not further enhanced in PyMT;ctsb −/− mice. Furthermore, lung colonization studies of PyMT Cells with different CTSB genotypes injected into congenic wild-type mice and in vitro Matrigel invasion assays confirmed a specific role for tumor-derived CTSB in invasion and metastasis. Interestingly, Cell surface labeling of cysteine cathepsins by the active site probe DCG-04 detected up-regulation of cathepsin X on PyMT;ctsb −/− Cells. Treatment of Cells with a neutralizing anti-cathepsin X antibody significantly reduced Matrigel invasion of PyMT;ctsb −/− Cells but did not affect invasion of PyMT;ctsb +/+ or PyMT;ctsb +/− Cells, indicating a compensatory function of cathepsin X in CTSB-deficient tumor Cells. Finally, an adoptive transfer model, in which ctsb +/+ , ctsb +/− , and ctsb −/− recipient mice were challenged with PyMT;ctsb +/+ Cells, was used to address the role of Stroma-derived CTSB in lung metastasis formation. Notably, ctsb −/− mice showed reduced number and volume of lung colonies, and infiltrating macrophages showed a strongly up-regulated expression of CTSB within metastatic Cell populations. These results indicate that both cancer Cell–derived and Stroma Cell–derived (i.e., macrophages) CTSB plays an important role in tumor progression and metastasis. (Cancer Res 2006; 66(10): 5242-50)
Tomoji Kawabata - One of the best experts on this subject based on the ideXlab platform.
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antifibrotic action of pirfenidone and prednisolone different effects on pulmonary cytokines and growth factors in bleomycin induced murine pulmonary fibrosis
2008Co-Authors: Hisashi Oku, Toshikatsu Shimizu, Tomoji Kawabata, Morio Nagira, Ichiro Hikita, Azumi Ueyama, Shuuichi Matsushima, Mikinori Torii, Akinori ArimuraAbstract:Pirfenidone, a broad-spectrum antifibrotic agent, is known to have efficacy in certain fibrotic disease models, and is under clinical trials in patients with idiopathic pulmonary fibrosis. We investigated the antifibrotic effect of pirfenidone, and its regulatory effect on various pulmonary cytokines, in bleomycin-induced lung fibrosis in mice at the protein level, using prednisolone as a reference agent. Pirfenidone attenuated the bleomycin-induced pulmonary fibrosis at a minimum effective dose of 30 mg/kg/day t.i.d. from the analysis of lung hydroxyproline content. Both pirfenidone (30, 100 mg/kg/day t.i.d) and prednisolone (3, 15 mg/kg/day q.d.) suppressed lung inflammatory edema; however, prednisolone failed to suppress pulmonary fibrosis, which was significantly suppressed only by pirfenidone. Both pirfenidone and prednisolone suppressed the increase in lung interleukin (IL)-1beta, IL-6, IL-12p40 and monocyte chemoattractant protein (MCP)-1 levels induced by bleomycin. On the other hand, pirfenidone prevented the bleomycin-induced decrease in lung interferon (IFN)-gamma levels, while prednisolone had no such effect. Furthermore, pirfenidone suppressed elevation of lung basic-fibroblast growth factor (bFGF) and transforming growth factor (TGF)-beta1 levels, but prednisolone had no such effect. The increases in lung Stroma Cell derived factor (SDF)-1alpha and IL-18 were also suppressed. These findings suggest that pirfenidone exerts its antifibrotic effect through regulation of lung IFN-gamma, bFGF and TGF-beta1 levels during the development of bleomycin-induced pulmonary fibrosis in mice. The effect on SDF-1alpha and IL-18 levels may also be related to the antifibrotic effects of pirfenidone.
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antifibrotic action of pirfenidone and prednisolone different effects on pulmonary cytokines and growth factors in bleomycin induced murine pulmonary fibrosis
2008Co-Authors: Toshikatsu Shimizu, Tomoji Kawabata, Morio Nagira, Ichiro Hikita, Azumi Ueyama, Shuuichi Matsushima, Mikinori Torii, Akinori ArimuraAbstract:Abstract Pirfenidone, a broad-spectrum antifibrotic agent, is known to have efficacy in certain fibrotic disease models, and is under clinical trials in patients with idiopathic pulmonary fibrosis. We investigated the antifibrotic effect of pirfenidone, and its regulatory effect on various pulmonary cytokines, in bleomycin-induced lung fibrosis in mice at the protein level, using prednisolone as a reference agent. Pirfenidone attenuated the bleomycin-induced pulmonary fibrosis at a minimum effective dose of 30 mg/kg/day t.i.d. from the analysis of lung hydroxyproline content. Both pirfenidone (30, 100 mg/kg/day t.i.d) and prednisolone (3, 15 mg/kg/day q.d.) suppressed lung inflammatory edema; however, prednisolone failed to suppress pulmonary fibrosis, which was significantly suppressed only by pirfenidone. Both pirfenidone and prednisolone suppressed the increase in lung interleukin (IL)-1β, IL-6, IL-12p40 and monocyte chemoattractant protein (MCP)-1 levels induced by bleomycin. On the other hand, pirfenidone prevented the bleomycin-induced decrease in lung interferon (IFN)-γ levels, while prednisolone had no such effect. Furthermore, pirfenidone suppressed elevation of lung basic-fibroblast growth factor (bFGF) and transforming growth factor (TGF)-β1 levels, but prednisolone had no such effect. The increases in lung Stroma Cell derived factor (SDF)-1α and IL-18 were also suppressed. These findings suggest that pirfenidone exerts its antifibrotic effect through regulation of lung IFN-γ, bFGF and TGF-β1 levels during the development of bleomycin-induced pulmonary fibrosis in mice. The effect on SDF-1α and IL-18 levels may also be related to the antifibrotic effects of pirfenidone.
Morio Nagira - One of the best experts on this subject based on the ideXlab platform.
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antifibrotic action of pirfenidone and prednisolone different effects on pulmonary cytokines and growth factors in bleomycin induced murine pulmonary fibrosis
2008Co-Authors: Hisashi Oku, Toshikatsu Shimizu, Tomoji Kawabata, Morio Nagira, Ichiro Hikita, Azumi Ueyama, Shuuichi Matsushima, Mikinori Torii, Akinori ArimuraAbstract:Pirfenidone, a broad-spectrum antifibrotic agent, is known to have efficacy in certain fibrotic disease models, and is under clinical trials in patients with idiopathic pulmonary fibrosis. We investigated the antifibrotic effect of pirfenidone, and its regulatory effect on various pulmonary cytokines, in bleomycin-induced lung fibrosis in mice at the protein level, using prednisolone as a reference agent. Pirfenidone attenuated the bleomycin-induced pulmonary fibrosis at a minimum effective dose of 30 mg/kg/day t.i.d. from the analysis of lung hydroxyproline content. Both pirfenidone (30, 100 mg/kg/day t.i.d) and prednisolone (3, 15 mg/kg/day q.d.) suppressed lung inflammatory edema; however, prednisolone failed to suppress pulmonary fibrosis, which was significantly suppressed only by pirfenidone. Both pirfenidone and prednisolone suppressed the increase in lung interleukin (IL)-1beta, IL-6, IL-12p40 and monocyte chemoattractant protein (MCP)-1 levels induced by bleomycin. On the other hand, pirfenidone prevented the bleomycin-induced decrease in lung interferon (IFN)-gamma levels, while prednisolone had no such effect. Furthermore, pirfenidone suppressed elevation of lung basic-fibroblast growth factor (bFGF) and transforming growth factor (TGF)-beta1 levels, but prednisolone had no such effect. The increases in lung Stroma Cell derived factor (SDF)-1alpha and IL-18 were also suppressed. These findings suggest that pirfenidone exerts its antifibrotic effect through regulation of lung IFN-gamma, bFGF and TGF-beta1 levels during the development of bleomycin-induced pulmonary fibrosis in mice. The effect on SDF-1alpha and IL-18 levels may also be related to the antifibrotic effects of pirfenidone.
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antifibrotic action of pirfenidone and prednisolone different effects on pulmonary cytokines and growth factors in bleomycin induced murine pulmonary fibrosis
2008Co-Authors: Toshikatsu Shimizu, Tomoji Kawabata, Morio Nagira, Ichiro Hikita, Azumi Ueyama, Shuuichi Matsushima, Mikinori Torii, Akinori ArimuraAbstract:Abstract Pirfenidone, a broad-spectrum antifibrotic agent, is known to have efficacy in certain fibrotic disease models, and is under clinical trials in patients with idiopathic pulmonary fibrosis. We investigated the antifibrotic effect of pirfenidone, and its regulatory effect on various pulmonary cytokines, in bleomycin-induced lung fibrosis in mice at the protein level, using prednisolone as a reference agent. Pirfenidone attenuated the bleomycin-induced pulmonary fibrosis at a minimum effective dose of 30 mg/kg/day t.i.d. from the analysis of lung hydroxyproline content. Both pirfenidone (30, 100 mg/kg/day t.i.d) and prednisolone (3, 15 mg/kg/day q.d.) suppressed lung inflammatory edema; however, prednisolone failed to suppress pulmonary fibrosis, which was significantly suppressed only by pirfenidone. Both pirfenidone and prednisolone suppressed the increase in lung interleukin (IL)-1β, IL-6, IL-12p40 and monocyte chemoattractant protein (MCP)-1 levels induced by bleomycin. On the other hand, pirfenidone prevented the bleomycin-induced decrease in lung interferon (IFN)-γ levels, while prednisolone had no such effect. Furthermore, pirfenidone suppressed elevation of lung basic-fibroblast growth factor (bFGF) and transforming growth factor (TGF)-β1 levels, but prednisolone had no such effect. The increases in lung Stroma Cell derived factor (SDF)-1α and IL-18 were also suppressed. These findings suggest that pirfenidone exerts its antifibrotic effect through regulation of lung IFN-γ, bFGF and TGF-β1 levels during the development of bleomycin-induced pulmonary fibrosis in mice. The effect on SDF-1α and IL-18 levels may also be related to the antifibrotic effects of pirfenidone.
