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Foreign body granulomatous inflammation increases the sensitivity of splenocytes to immunomodulation by 1,25-dihydroxyvitamin D3
Affiliation:1. Sackler School of Medicine, Tel Aviv University, Petah Tikva 49100, Israel;2. Metabolic Disease Unit, Petah Tikva 49100, Israel;4. Institute of Nephrology and Hypertension, Petah Tikva 49100, Israel;3. Felsenstein Medical Research Center, Beilinson Medical Center, Petah Tikva 49100, Israel;1. Division of Epidemiology, Department of Environmental and Public Health Sciences, University of Cincinnati College of Medicine, Cincinnati, OH, USA;2. School of Human Services, University of Cincinnati, Cincinnati, OH, USA;3. Division of Asthma Research, Cincinnati Children''s Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH, USA;4. Division of Emergency Medicine, Cincinnati Children''s Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH, USA;5. Department of Biostatistics and Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA;6. General and Community Pediatrics, Cincinnati Children''s Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH, USA;1. School of Electrical Engineering, Yanshan University, Qinhuangdao City, Hebei Province, China;2. Hebei University of Environmental Engineering, Qinhuangdao City, Hebei Province, China;1. Aristotle University of Thessaloniki, School of Geology, Lab. of Engineering Geology and Hydrogeology, 54124, Thessaloniki, Greece;2. Aristotle University of Thessaloniki, School of Geology, Department of Mineralogy-Petrology-Economic Geology, 54124, Thessaloniki, Greece;3. Aristotle University of Thessaloniki, Department of Chemical Engineering, 54124, Thessaloniki, Greece;4. University of Copenhagen, Department of Geoscience and Natural Resource Management Nord CEE, Denmark;5. Aristotle University of Thessaloniki, School of Geology, Lab. of Applied Geophysics, 54124, Thessaloniki, Greece;6. Aristotle University of Thessaloniki, Department of Chemistry, Lab. of Chemical & Environmental Technology, 54124, Thessaloniki, Greece;1. Institute of Microelectronics, College of Optics and Electronic Technology, China Jiliang University, Hangzhou 310018, Zhejiang, China;2. Institute of Microelectronics, School of Physical Science & Technology, Lanzhou University, Lanzhou 730000, Gansu, China
Abstract:1,25-dihydroxyvitamin D3, the active metabolite of vitamin D, partially inhibits antigen and mitogen-driven lymphocyte stimulation. We studied the effect of granulomatous inflammation on the sensitivity of lymphocytes to 1,25-dihydroxyvitamin D3in vitro, measuring the inhibitory effect of 1,25-dihydroxyvitamin D3 on mitogenesis of splenocytes of mice with chronic inflammation induced by subcutaneous injection of talc. Systematic manifestations of the local inflammation included loss in body weight, splenomegaly, enhanced DNA synthesis by freshly isolated splenocytes and enhanced prostaglandin secretion by activated splenocytes. Splenocytes from animals with local inflammation were more susceptible to inhibition by 1,25-dihydroxyvitamin D3, but not by prosaglandin E2. This increased sensitivity to 1,25-dihydroxyvitamin D3 was abolished by blocking prostaglandin synthesis in splenocyte cultures with indomethacin and was restored by adding prostaglandin E2. This effect cannot be attributed to enhanced prostaglandin synthesis in the presence of 1,25-dihydroxyvitamin D3, but is probably due to a qualitative change in the response of splenocytes from inflamed animals to the combined action of 1,25-dihydroxyvitamin D3 and prostaglandin E2.
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