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Linomide prevents the lethal effect of anti-fas antibody and reduces fas-mediated ceramide production in mouse hepatocytes

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dc.creator Redondo, Clara
dc.creator Flores, Ignacio
dc.creator González García, Ana
dc.creator Nagata, Shigekazu
dc.creator Carrera, Ana C.
dc.creator Mérida, Isabel
dc.creator Martínez-Alonso, Carlos
dc.date 2008-04-16T10:06:04Z
dc.date 2008-04-16T10:06:04Z
dc.date 1996-09
dc.date.accessioned 2017-01-31T01:02:26Z
dc.date.available 2017-01-31T01:02:26Z
dc.identifier The Journal of Clinical Investigation, vol. 98(5), pp. 1245-1252, (1996)
dc.identifier 0021-9738
dc.identifier http://hdl.handle.net/10261/3616
dc.identifier 10.1172/JCI118908
dc.identifier.uri http://dspace.mediu.edu.my:8181/xmlui/handle/10261/3616
dc.description Fas is an apoptosis-signaling receptor molecule expressed in vivo on thymocytes, liver, heart, and ovary. In vivo administration of the anti-Fas Jo2 antibody in mice induces severe apoptotic liver damage leading to fulminant hepatitis and death. Linomide, a quinoline 3-carboxamide, inhibits apoptosis of B and T cells induced by various stimuli including viruses, superantigens, and glucocorticoids. Mice treated with linomide survived the lethal effect of anti-Fas antibody, did not accumulate ceramide in hepatocytes, and recovered liver structure and function within 96 h of anti-Fas injection, as confirmed by histology and glutamic oxalacetic transaminase, glutamic pyruvic transaminase, and lactate dehydrogenase levels. Surviving mice showed severe depletion of cortical thymocytes, but medullar thymic cells expressing high CD3 and Fas levels also survived the treatment with anti-Fas in the presence of linomide. Heart, lung, and ovary showed no signs of apoptosis promoted by Fas ligation. These results suggest that linomide prevents cell death triggered by Fas ligation and can be useful for therapeutic intervention in fulminant hepatitis
dc.description Peer reviewed
dc.format 968692 bytes
dc.format application/pdf
dc.language eng
dc.publisher American Society for Clinical Investigation
dc.rights openAccess
dc.subject Apoptosis
dc.subject Ceramide
dc.subject Fas
dc.subject Fulminant hepatitis
dc.subject Liver
dc.title Linomide prevents the lethal effect of anti-fas antibody and reduces fas-mediated ceramide production in mouse hepatocytes
dc.type Artículo


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