Attenuation of autoimmune disease in fas-deficient mice by treatment with a cytotoxic benzodiazepine
dc.contributor.author | Bednarski, Jeffrey J. | en_US |
dc.contributor.author | Warner, Roscoe L. | en_US |
dc.contributor.author | Rao, Tharaknath | en_US |
dc.contributor.author | Leonetti, Francesco | en_US |
dc.contributor.author | Yung, Raymond L. | en_US |
dc.contributor.author | Richardson, Bruce C. | en_US |
dc.contributor.author | Johnson, Kent J. | en_US |
dc.contributor.author | Ellman, Jonathan A. | en_US |
dc.contributor.author | Opipari, Anthony W. | en_US |
dc.contributor.author | Glick, Gary D. | en_US |
dc.date.accessioned | 2006-04-19T13:27:43Z | |
dc.date.available | 2006-04-19T13:27:43Z | |
dc.date.issued | 2003-03 | en_US |
dc.identifier.citation | Bednarski, Jeffrey J.; Warner, Roscoe E.; Rao, Tharaknath; Leonetti, Francesco; Yung, Raymond; Richardson, Bruce C.; Johnson, Kent J.; Ellman, Jonathan A.; Opipari, Anthony W.; Glick, Gary D. (2003)."Attenuation of autoimmune disease in fas-deficient mice by treatment with a cytotoxic benzodiazepine." Arthritis & Rheumatism 48(3): 757-766. <http://hdl.handle.net/2027.42/34307> | en_US |
dc.identifier.issn | 0004-3591 | en_US |
dc.identifier.issn | 1529-0131 | en_US |
dc.identifier.uri | https://hdl.handle.net/2027.42/34307 | |
dc.identifier.uri | http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=retrieve&db=pubmed&list_uids=12632430&dopt=citation | en_US |
dc.description.abstract | Objective Elimination of autoreactive cells relies on Fas-dependent activation-induced cell death mechanisms, an important component of peripheral tolerance. Defects in Fas or its cognate ligand lead to inefficient activation-induced cell death and are specific causes of lymphoproliferative and autoimmune diseases. The present study was undertaken to investigate a novel 1,4-benzodiazepine (Bz-423) that induces apoptosis and limits autoimmune disease in NZB/NZW mice, to determine its activity against lupus-like disease associated with defective Fas expression. We investigated the Fas-dependence of its cytotoxic actions, its therapeutic potential in mice deficient in Fas, and its therapeutic mechanism of action. Methods Primary lymphocytes isolated from Fas-deficient MRL/ MpJ-Fas lpr (MRL- lpr ) mice were tested for sensitivity to Bz-423. Bz-423 was administered to MRL- lpr mice for short (1-week) or long (14-week) periods, and its effects on cell survival were determined along with measures of nephritis, arthritis, antibody titers, and Th subpopulations. BALB/c mice were similarly treated to determine if Bz-423 alters normal immune functions in vivo. Results Administration of Bz-423 to MRL- lpr mice significantly reduced autoimmune disease including glomerulonephritis and arthritis. Treatment was associated with decreases in CD4+ T cells and an alteration in the Th1/Th2 balance. At the therapeutic dosage, Bz-423 did not interfere with normal T and B cell responses in BALB/c mice, suggesting that this agent is not globally immunosuppressive. Conclusion Bz-423 is a novel immunomodulatory agent that is active against disease even in the context of defective Fas signaling. It is a leading compound for further investigation into the development of selective therapies for lupus. | en_US |
dc.format.extent | 177146 bytes | |
dc.format.extent | 3118 bytes | |
dc.format.mimetype | application/pdf | |
dc.format.mimetype | text/plain | |
dc.language.iso | en_US | |
dc.publisher | Wiley Subscription Services, Inc., A Wiley Company | en_US |
dc.subject.other | Life and Medical Sciences | en_US |
dc.title | Attenuation of autoimmune disease in fas-deficient mice by treatment with a cytotoxic benzodiazepine | en_US |
dc.type | Article | en_US |
dc.rights.robots | IndexNoFollow | en_US |
dc.subject.hlbsecondlevel | Geriatrics | en_US |
dc.subject.hlbtoplevel | Health Sciences | en_US |
dc.description.peerreviewed | Peer Reviewed | en_US |
dc.contributor.affiliationum | University of Michigan, Ann Arbor | en_US |
dc.contributor.affiliationum | University of Michigan, Ann Arbor | en_US |
dc.contributor.affiliationum | University of Michigan, Ann Arbor | en_US |
dc.contributor.affiliationum | University of Michigan, Ann Arbor | en_US |
dc.contributor.affiliationum | University of Michigan, Ann Arbor | en_US |
dc.contributor.affiliationum | University of Michigan, Ann Arbor | en_US |
dc.contributor.affiliationum | University of Michigan, Ann Arbor ; University of Michigan, 930 North University, Ann Arbor, MI 48109-1055 | en_US |
dc.contributor.affiliationum | University of Michigan, Ann Arbor ; University of Michigan, 930 North University, Ann Arbor, MI 48109-1055 | en_US |
dc.contributor.affiliationother | University of California, Berkeley | en_US |
dc.contributor.affiliationother | University of California, Berkeley | en_US |
dc.identifier.pmid | 12632430 | en_US |
dc.description.bitstreamurl | http://deepblue.lib.umich.edu/bitstream/2027.42/34307/1/10968_ftp.pdf | en_US |
dc.identifier.doi | http://dx.doi.org/10.1002/art.10968 | en_US |
dc.identifier.source | Arthritis & Rheumatism | en_US |
dc.owningcollname | Interdisciplinary and Peer-Reviewed |
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