LTB4 and BLT1 in inflammatory arthritis |
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| Affiliation: | 1. Department of Dermatology, Allergology and Venereology, University of Lübeck, Lübeck, Germany;2. Institute of Experimental Dermatology, University of Lübeck, Lübeck, Germany;3. Department of Experimental Hematology, Sanquin Research Institute, Amsterdam, The Netherlands;4. Institut für Medizinische Biometrie und Statistik, Universität zu Lübeck, Universitätsklinikum Schleswig-Holstein, Campus Lübeck, Lübeck, Germany;5. Zentrum für Klinische Studien, Universität zu Lübeck, Lübeck, Germany;6. Department of Transfusion Medicine, University of Lübeck, Lübeck, Germany;7. Institute of Clinical Molecular Biology, Christian-Albrechts-University, Kiel, Germany;8. Institute of Epidemiology, Christian-Albrechts-University, Kiel, Germany;10. Department of Dermatology, Allergology and Venereology, Christian-Albrechts-University, Kiel, Germany;11. Department of Dermatology, Allergology and Venereology, University Hospital Würzburg, Würzburg, Germany;12. Department of Dermatology and Allergology, Ludwig Maximilian University, Munich, Germany;13. Department of Dermatology and Allergology, Philipp University of Marburg, Marburg, Germany;1. Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Spain;2. Unidad de Gestión Clínica Reumatología, Hospital Universitario Reina Sofía, Córdoba, Spain;3. Departamento de Medicina (Medicina, Dermatología y Otorrinolaringología), Universidad de Córdoba, Spain;4. Centro Regional de Hemodonación, Universidad de Murcia, IMIB-Arrixaca, Spain;5. Departamento de Biología Celular, Fisiología e Inmunología, Universidad de Córdoba, Campus de Excelencia Internacional Agroalimentario, ceiA3, Córdoba, Spain;1. School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, China;2. School of Pharmacy, Ningxia Medical University, Yinchuan 750004, China;1. Storr Liver Centre, Westmead Millennium Institute and Westmead Hospital, University of Sydney, Sydney, New South Wales 2145, Australia;2. Liver and Pancreatobiliary Diseases Research Centre, Digestive Disease Research Institute, Shariati Hospital, Tehran university of Medical Sciences, Tehran, Iran |
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| Abstract: | Inflammatory arthritis, including rheumatoid arthritis (RA), is characterized by infiltration of inflammatory cells into the joints. Biological agents targeting TNF-α and IL-6 dramatically improve RA. However, some RA patients do not respond to current treatments and these broadly active upstream biological agents increase the risk of severe infection. Therefore, there remains a need for other effective and safe treatments for RA. Many studies have implicated that blockade of leukotriene B4 (LTB4) and its high affinity receptor BLT1 dramatically suppress arthritis in animal models. In addition, levels of LTB4 in serum, synovial fluid and synovial tissue are increased in RA patients compared to healthy donors or osteoarthritis patients. These data suggest that LTB4 and BLT1 likely contribute to the pathogenesis of human RA. However, several clinical trials inhibiting BLT1 in RA were not successful. Our recent data revealed that LTB4 is a key mediator in a complement, lipid, cytokine and chemokine cascade that first initiates and then sustains neutrophilic inflammation in inflammatory arthritis. These new mechanistic studies suggest novel ways to target the LTB4-BLT1 pathway for the treatment of RA and other inflammatory diseases. |
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| Keywords: | Leukotriene B4 Leukotriene B4 receptor Rheumatoid arthritis Inflammatory arthritis Leukocytes |
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