The Experts below are selected from a list of 360 Experts worldwide ranked by ideXlab platform
Gary S Firestein - One of the best experts on this subject based on the ideXlab platform.
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anti inflammatory effects of abt 702 a novel non nucleoside adenosine kinase inhibitor in rat adjuvant arthritis
Journal of Pharmacology and Experimental Therapeutics, 2001Co-Authors: David L Boyle, Chihhung Lee, Michael Williams, Gary S FiresteinAbstract:Adenosine (ADO) is a homeostatic inhibitory Autocoid that is released at sites of inflammation and tissue injury, and exerts anti-inflammatory effects via multiple interactions at ADO receptor subtypes. Inhibition of ADO kinase (AK) increases extracellular ADO concentrations and AK inhibitors have demonstrated ADO-mediated anti-inflammatory effects in acute models of inflammation. To evaluate the potential utility of this approach in chronic inflammation, a novel, potent, and selective non-nucleoside AK inhibitor, ABT-702, was tested in the rat adjuvant arthritis model. Animals were immunized with complete Freund's adjuvant on day 0 and were treated with vehicle or ABT-702 (20 mg/kg/b.i.d. p.o.) beginning on day 8. ABT-702 significantly inhibited arthritis as determined by paw volume. In addition, histologic and radiographic evidence of bone and cartilage destruction was significantly decreased in the treated group. Coadministration of the ADO receptor antagonist theophylline attenuated the anti-inflammatory effects of ABT-702, suggesting that this action was mediated through endogenous ADO release. To evaluate the mechanism of chondroprotection, Northern blot and electrophoretic mobility shift assays were performed on joints samples. These studies demonstrated that ABT-702 suppressed collagenase and stromelysin gene expression in treated animals. In addition, the activator protein-1 and nuclear factor-kappaB binding activity was also decreased. Therefore, ABT-702 inhibited clinical, radiographic, and histologic evidence of chronic inflammatory arthritis. The mechanism of joint protection is likely related to suppressed transcription factor activation and matrix metalloproteinase gene expression.
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Anti-inflammatory effects of ABT-702, a novel non-nucleoside adenosine kinase inhibitor, in rat adjuvant arthritis
2001Co-Authors: David L Boyle, Chihhung Lee, Michael Williams, Elizabeth A. Kowaluk, Michael F. Jarvis, Shripad S. Bhagwat, Gary S FiresteinAbstract:Adenosine (ADO) is a homeostatic inhibitory Autocoid that is released at sites of inflammation and tissue injury, and exerts anti-inflammatory effects via multiple interactions at ADO re-ceptor subtypes. Inhibition of ADO kinase (AK) increases extra-cellular ADO concentrations and AK inhibitors have demon-strated ADO-mediated anti-inflammatory effects in acute models of inflammation. To evaluate the potential utility of this approach in chronic inflammation, a novel, potent, and selec-tive non-nucleoside AK inhibitor, ABT-702, was tested in the rat adjuvant arthritis model. Animals were immunized with com-plete Freund’s adjuvant on day 0 and were treated with vehicle or ABT-702 (20 mg/kg/b.i.d. p.o.) beginning on day 8. ABT-702 significantly inhibited arthritis as determined by paw volume. In addition, histologic and radiographic evidence of bone an
David L Boyle - One of the best experts on this subject based on the ideXlab platform.
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anti inflammatory effects of abt 702 a novel non nucleoside adenosine kinase inhibitor in rat adjuvant arthritis
Journal of Pharmacology and Experimental Therapeutics, 2001Co-Authors: David L Boyle, Chihhung Lee, Michael Williams, Gary S FiresteinAbstract:Adenosine (ADO) is a homeostatic inhibitory Autocoid that is released at sites of inflammation and tissue injury, and exerts anti-inflammatory effects via multiple interactions at ADO receptor subtypes. Inhibition of ADO kinase (AK) increases extracellular ADO concentrations and AK inhibitors have demonstrated ADO-mediated anti-inflammatory effects in acute models of inflammation. To evaluate the potential utility of this approach in chronic inflammation, a novel, potent, and selective non-nucleoside AK inhibitor, ABT-702, was tested in the rat adjuvant arthritis model. Animals were immunized with complete Freund's adjuvant on day 0 and were treated with vehicle or ABT-702 (20 mg/kg/b.i.d. p.o.) beginning on day 8. ABT-702 significantly inhibited arthritis as determined by paw volume. In addition, histologic and radiographic evidence of bone and cartilage destruction was significantly decreased in the treated group. Coadministration of the ADO receptor antagonist theophylline attenuated the anti-inflammatory effects of ABT-702, suggesting that this action was mediated through endogenous ADO release. To evaluate the mechanism of chondroprotection, Northern blot and electrophoretic mobility shift assays were performed on joints samples. These studies demonstrated that ABT-702 suppressed collagenase and stromelysin gene expression in treated animals. In addition, the activator protein-1 and nuclear factor-kappaB binding activity was also decreased. Therefore, ABT-702 inhibited clinical, radiographic, and histologic evidence of chronic inflammatory arthritis. The mechanism of joint protection is likely related to suppressed transcription factor activation and matrix metalloproteinase gene expression.
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Anti-inflammatory effects of ABT-702, a novel non-nucleoside adenosine kinase inhibitor, in rat adjuvant arthritis
2001Co-Authors: David L Boyle, Chihhung Lee, Michael Williams, Elizabeth A. Kowaluk, Michael F. Jarvis, Shripad S. Bhagwat, Gary S FiresteinAbstract:Adenosine (ADO) is a homeostatic inhibitory Autocoid that is released at sites of inflammation and tissue injury, and exerts anti-inflammatory effects via multiple interactions at ADO re-ceptor subtypes. Inhibition of ADO kinase (AK) increases extra-cellular ADO concentrations and AK inhibitors have demon-strated ADO-mediated anti-inflammatory effects in acute models of inflammation. To evaluate the potential utility of this approach in chronic inflammation, a novel, potent, and selec-tive non-nucleoside AK inhibitor, ABT-702, was tested in the rat adjuvant arthritis model. Animals were immunized with com-plete Freund’s adjuvant on day 0 and were treated with vehicle or ABT-702 (20 mg/kg/b.i.d. p.o.) beginning on day 8. ABT-702 significantly inhibited arthritis as determined by paw volume. In addition, histologic and radiographic evidence of bone an
Chihhung Lee - One of the best experts on this subject based on the ideXlab platform.
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anti inflammatory effects of abt 702 a novel non nucleoside adenosine kinase inhibitor in rat adjuvant arthritis
Journal of Pharmacology and Experimental Therapeutics, 2001Co-Authors: David L Boyle, Chihhung Lee, Michael Williams, Gary S FiresteinAbstract:Adenosine (ADO) is a homeostatic inhibitory Autocoid that is released at sites of inflammation and tissue injury, and exerts anti-inflammatory effects via multiple interactions at ADO receptor subtypes. Inhibition of ADO kinase (AK) increases extracellular ADO concentrations and AK inhibitors have demonstrated ADO-mediated anti-inflammatory effects in acute models of inflammation. To evaluate the potential utility of this approach in chronic inflammation, a novel, potent, and selective non-nucleoside AK inhibitor, ABT-702, was tested in the rat adjuvant arthritis model. Animals were immunized with complete Freund's adjuvant on day 0 and were treated with vehicle or ABT-702 (20 mg/kg/b.i.d. p.o.) beginning on day 8. ABT-702 significantly inhibited arthritis as determined by paw volume. In addition, histologic and radiographic evidence of bone and cartilage destruction was significantly decreased in the treated group. Coadministration of the ADO receptor antagonist theophylline attenuated the anti-inflammatory effects of ABT-702, suggesting that this action was mediated through endogenous ADO release. To evaluate the mechanism of chondroprotection, Northern blot and electrophoretic mobility shift assays were performed on joints samples. These studies demonstrated that ABT-702 suppressed collagenase and stromelysin gene expression in treated animals. In addition, the activator protein-1 and nuclear factor-kappaB binding activity was also decreased. Therefore, ABT-702 inhibited clinical, radiographic, and histologic evidence of chronic inflammatory arthritis. The mechanism of joint protection is likely related to suppressed transcription factor activation and matrix metalloproteinase gene expression.
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Anti-inflammatory effects of ABT-702, a novel non-nucleoside adenosine kinase inhibitor, in rat adjuvant arthritis
2001Co-Authors: David L Boyle, Chihhung Lee, Michael Williams, Elizabeth A. Kowaluk, Michael F. Jarvis, Shripad S. Bhagwat, Gary S FiresteinAbstract:Adenosine (ADO) is a homeostatic inhibitory Autocoid that is released at sites of inflammation and tissue injury, and exerts anti-inflammatory effects via multiple interactions at ADO re-ceptor subtypes. Inhibition of ADO kinase (AK) increases extra-cellular ADO concentrations and AK inhibitors have demon-strated ADO-mediated anti-inflammatory effects in acute models of inflammation. To evaluate the potential utility of this approach in chronic inflammation, a novel, potent, and selec-tive non-nucleoside AK inhibitor, ABT-702, was tested in the rat adjuvant arthritis model. Animals were immunized with com-plete Freund’s adjuvant on day 0 and were treated with vehicle or ABT-702 (20 mg/kg/b.i.d. p.o.) beginning on day 8. ABT-702 significantly inhibited arthritis as determined by paw volume. In addition, histologic and radiographic evidence of bone an
Michael Williams - One of the best experts on this subject based on the ideXlab platform.
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anti inflammatory effects of abt 702 a novel non nucleoside adenosine kinase inhibitor in rat adjuvant arthritis
Journal of Pharmacology and Experimental Therapeutics, 2001Co-Authors: David L Boyle, Chihhung Lee, Michael Williams, Gary S FiresteinAbstract:Adenosine (ADO) is a homeostatic inhibitory Autocoid that is released at sites of inflammation and tissue injury, and exerts anti-inflammatory effects via multiple interactions at ADO receptor subtypes. Inhibition of ADO kinase (AK) increases extracellular ADO concentrations and AK inhibitors have demonstrated ADO-mediated anti-inflammatory effects in acute models of inflammation. To evaluate the potential utility of this approach in chronic inflammation, a novel, potent, and selective non-nucleoside AK inhibitor, ABT-702, was tested in the rat adjuvant arthritis model. Animals were immunized with complete Freund's adjuvant on day 0 and were treated with vehicle or ABT-702 (20 mg/kg/b.i.d. p.o.) beginning on day 8. ABT-702 significantly inhibited arthritis as determined by paw volume. In addition, histologic and radiographic evidence of bone and cartilage destruction was significantly decreased in the treated group. Coadministration of the ADO receptor antagonist theophylline attenuated the anti-inflammatory effects of ABT-702, suggesting that this action was mediated through endogenous ADO release. To evaluate the mechanism of chondroprotection, Northern blot and electrophoretic mobility shift assays were performed on joints samples. These studies demonstrated that ABT-702 suppressed collagenase and stromelysin gene expression in treated animals. In addition, the activator protein-1 and nuclear factor-kappaB binding activity was also decreased. Therefore, ABT-702 inhibited clinical, radiographic, and histologic evidence of chronic inflammatory arthritis. The mechanism of joint protection is likely related to suppressed transcription factor activation and matrix metalloproteinase gene expression.
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Anti-inflammatory effects of ABT-702, a novel non-nucleoside adenosine kinase inhibitor, in rat adjuvant arthritis
2001Co-Authors: David L Boyle, Chihhung Lee, Michael Williams, Elizabeth A. Kowaluk, Michael F. Jarvis, Shripad S. Bhagwat, Gary S FiresteinAbstract:Adenosine (ADO) is a homeostatic inhibitory Autocoid that is released at sites of inflammation and tissue injury, and exerts anti-inflammatory effects via multiple interactions at ADO re-ceptor subtypes. Inhibition of ADO kinase (AK) increases extra-cellular ADO concentrations and AK inhibitors have demon-strated ADO-mediated anti-inflammatory effects in acute models of inflammation. To evaluate the potential utility of this approach in chronic inflammation, a novel, potent, and selec-tive non-nucleoside AK inhibitor, ABT-702, was tested in the rat adjuvant arthritis model. Animals were immunized with com-plete Freund’s adjuvant on day 0 and were treated with vehicle or ABT-702 (20 mg/kg/b.i.d. p.o.) beginning on day 8. ABT-702 significantly inhibited arthritis as determined by paw volume. In addition, histologic and radiographic evidence of bone an
Gyorgy Hasko - One of the best experts on this subject based on the ideXlab platform.
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adenosine an endogenous regulator of innate immunity
Trends in Immunology, 2004Co-Authors: Gyorgy Hasko, Bruce N CronsteinAbstract:Although inflammatory and immunological reactions protect the host from invasion by microorganisms and eliminate debris at sites of tissue injury, they can also be responsible for significant tissue damage. Thus, regulatory mechanisms that limit damage from an overly exuberant immune response have evolved. It is increasingly apparent that adenosine, a purine nucleoside that is elaborated at injured and inflamed sites, has a central role in the regulation of inflammatory responses and in limiting inflammatory tissue destruction. Adenosine, called a ‘retaliatory metabolite’ because it is a regulatory Autocoid that is generated as a result of cellular injury or stress, interacts with specific G protein-coupled receptors on inflammatory and immune cells to regulate their function. The effects of adenosine, acting at its receptors, on the functions of the cells that mediate innate immune responses, will be reviewed.
